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FDA noncommittal on e-cigarette action
on when the agency would act and what actions it was planning on taking.
“I was actually shocked that, in a hearing that is focused in part on the youth vaping epidemic [that] your testimony, both written and oral here, made no mention of the administration’s Sept. 11 announcement that it intended to clear the market of all unauthorized non–tobacco-flavored vaping products,” said Patty Murray (D-Wash.), ranking member of the Senate Health, Education, Labor and Pensions Committee, during a Nov. 13 hearing to Mitchell Zeller, director of the FDA’s Center for Tobacco Products. “Why is that not included in your testimony?”
Director Zeller would only offer a vague response, testifying that the agency is “committed to doing everything that we can to prevent kids from using any tobacco product, including e-cigarettes, and that we are continuing to develop a policy approach that aligns with that concern.”
When Sen. Murray pressed further, Director Zeller deflected: “I think that any questions that the committee has about the announcement that the White House and anything related to what remains a deliberative process on policy is best referred to the White House itself.”
He would not even offer any perspective on when the FDA might take actual regulatory action when asked about it by Sen. Murray.
“I can’t give you a specific timeline, Senator, other than to say that the deliberative process continues,” Director Zeller responded, telling her that “I really would refer you and the committee to the White House to ask specific questions about where we are.”
The hearing, called to examine the response to lung illnesses and rising youth e-cigarette usage, shed no new light on the issue. And while Director Zeller outlined the numerous educational campaigns being aimed at convincing youth to not use e-cigarettes, Committee Chairman Lamar Alexander (R-Tenn.) questioned whether the FDA was doing an adequate job.
The FDA, from late 2017 to the end of 2020, “will wind up investing about $150 million in a massive, multimedia public education campaign to get the word out to kids” on the dangers of vaping, Director Zeller said, adding that the agency is “aggressively enforcing” youth access restrictions in targeting sellers of e-cigarette products to minors.
“Well, obviously we are not making much progress with youth use ... if one in four of American high schoolers, according to your statistics, are using e-cigarettes,” Sen. Alexander said.
While most on the committee were focused on the rising numbers of youth vaping and e-cigarette usage, Sen. Rand Paul (R-Ky.) cautioned that any regulatory action, particularly a ban on all flavored e-cigarette products, would adversely affect adults, particularly those who are turning to e-cigarettes as a smoking cessation tool.
His solution, noting that it is already illegal for kids to be purchasing vaping and e-cigarette products, was to increase the penalties for those found selling to minors, adding that “most adults are using the flavors as well” and it could lead them back to combustible tobacco products if they are prevented from accessing flavored e-cigarettes.
on when the agency would act and what actions it was planning on taking.
“I was actually shocked that, in a hearing that is focused in part on the youth vaping epidemic [that] your testimony, both written and oral here, made no mention of the administration’s Sept. 11 announcement that it intended to clear the market of all unauthorized non–tobacco-flavored vaping products,” said Patty Murray (D-Wash.), ranking member of the Senate Health, Education, Labor and Pensions Committee, during a Nov. 13 hearing to Mitchell Zeller, director of the FDA’s Center for Tobacco Products. “Why is that not included in your testimony?”
Director Zeller would only offer a vague response, testifying that the agency is “committed to doing everything that we can to prevent kids from using any tobacco product, including e-cigarettes, and that we are continuing to develop a policy approach that aligns with that concern.”
When Sen. Murray pressed further, Director Zeller deflected: “I think that any questions that the committee has about the announcement that the White House and anything related to what remains a deliberative process on policy is best referred to the White House itself.”
He would not even offer any perspective on when the FDA might take actual regulatory action when asked about it by Sen. Murray.
“I can’t give you a specific timeline, Senator, other than to say that the deliberative process continues,” Director Zeller responded, telling her that “I really would refer you and the committee to the White House to ask specific questions about where we are.”
The hearing, called to examine the response to lung illnesses and rising youth e-cigarette usage, shed no new light on the issue. And while Director Zeller outlined the numerous educational campaigns being aimed at convincing youth to not use e-cigarettes, Committee Chairman Lamar Alexander (R-Tenn.) questioned whether the FDA was doing an adequate job.
The FDA, from late 2017 to the end of 2020, “will wind up investing about $150 million in a massive, multimedia public education campaign to get the word out to kids” on the dangers of vaping, Director Zeller said, adding that the agency is “aggressively enforcing” youth access restrictions in targeting sellers of e-cigarette products to minors.
“Well, obviously we are not making much progress with youth use ... if one in four of American high schoolers, according to your statistics, are using e-cigarettes,” Sen. Alexander said.
While most on the committee were focused on the rising numbers of youth vaping and e-cigarette usage, Sen. Rand Paul (R-Ky.) cautioned that any regulatory action, particularly a ban on all flavored e-cigarette products, would adversely affect adults, particularly those who are turning to e-cigarettes as a smoking cessation tool.
His solution, noting that it is already illegal for kids to be purchasing vaping and e-cigarette products, was to increase the penalties for those found selling to minors, adding that “most adults are using the flavors as well” and it could lead them back to combustible tobacco products if they are prevented from accessing flavored e-cigarettes.
on when the agency would act and what actions it was planning on taking.
“I was actually shocked that, in a hearing that is focused in part on the youth vaping epidemic [that] your testimony, both written and oral here, made no mention of the administration’s Sept. 11 announcement that it intended to clear the market of all unauthorized non–tobacco-flavored vaping products,” said Patty Murray (D-Wash.), ranking member of the Senate Health, Education, Labor and Pensions Committee, during a Nov. 13 hearing to Mitchell Zeller, director of the FDA’s Center for Tobacco Products. “Why is that not included in your testimony?”
Director Zeller would only offer a vague response, testifying that the agency is “committed to doing everything that we can to prevent kids from using any tobacco product, including e-cigarettes, and that we are continuing to develop a policy approach that aligns with that concern.”
When Sen. Murray pressed further, Director Zeller deflected: “I think that any questions that the committee has about the announcement that the White House and anything related to what remains a deliberative process on policy is best referred to the White House itself.”
He would not even offer any perspective on when the FDA might take actual regulatory action when asked about it by Sen. Murray.
“I can’t give you a specific timeline, Senator, other than to say that the deliberative process continues,” Director Zeller responded, telling her that “I really would refer you and the committee to the White House to ask specific questions about where we are.”
The hearing, called to examine the response to lung illnesses and rising youth e-cigarette usage, shed no new light on the issue. And while Director Zeller outlined the numerous educational campaigns being aimed at convincing youth to not use e-cigarettes, Committee Chairman Lamar Alexander (R-Tenn.) questioned whether the FDA was doing an adequate job.
The FDA, from late 2017 to the end of 2020, “will wind up investing about $150 million in a massive, multimedia public education campaign to get the word out to kids” on the dangers of vaping, Director Zeller said, adding that the agency is “aggressively enforcing” youth access restrictions in targeting sellers of e-cigarette products to minors.
“Well, obviously we are not making much progress with youth use ... if one in four of American high schoolers, according to your statistics, are using e-cigarettes,” Sen. Alexander said.
While most on the committee were focused on the rising numbers of youth vaping and e-cigarette usage, Sen. Rand Paul (R-Ky.) cautioned that any regulatory action, particularly a ban on all flavored e-cigarette products, would adversely affect adults, particularly those who are turning to e-cigarettes as a smoking cessation tool.
His solution, noting that it is already illegal for kids to be purchasing vaping and e-cigarette products, was to increase the penalties for those found selling to minors, adding that “most adults are using the flavors as well” and it could lead them back to combustible tobacco products if they are prevented from accessing flavored e-cigarettes.
REPORTING FROM A SENATE HELP COMMITTEE HEARING
Halal nail polish
Ever heard of halal nail polish? As an expert on all things hair, skin, and nails, I was dismayed when I walked into my local nail salon and saw this new category of nail polish I’d never heard of before. About 10 halal nail polishes were available in an array of beautiful colors. This nail salon was already branded as “nontoxic,” carrying only “8-free” nail polishes, vegan, and cruelty-free body and cleaning products – as well as no acrylics or UV light devices used for drying manicured nails or processing gel nails. With the salon already providing 8-free nail polishes, what was the difference between those and halal nail polishes?
As I did my Google search while sitting in the salon chair, I got the answer both from salon employees and the Internet, and also found several other brands of halal nail polishes sold on Amazon.
The main ingredient in traditional nail lacquer is nitrocellulose, a mixture of an indigestible plant fiber. Once used for gunpowder and blast mining in the 19th century, today, nitrocellulose is used for many purposes for holding materials together, such as photography film, and diagnostic tests that involve antigen-antibody binding, such as pregnancy tests. In a bottle of traditional nail polish, nitrocellulose is dissolved in a chemical solvent (typically ethyl acetate), along with pigment colors and plasticizers. The solvent quickly evaporates and is what gives nail polish its chemical smell. Once painted on the nail, the solvent gradually evaporates away entirely and the nitrocellulose is left behind, drying into a solid film on the nail. The same solvent molecule is in nonacetone nail polish remover, which simply redissolves the nitrocellulose back into a liquid so it can be wiped off.
Some nail polish may also include “pearl essence” to give a shiny look, like the silvery iridescence of fish scales. In fact, these polishes have contained ground up iridescent fish scales, but because of overfishing and cost, cheaper mineral alternatives are now more commonly used to give this shiny appearance.
Traditional nail polish contains tight molecular bonds that are impermeable to air and water. The tight bonds create fewer interstitial spaces for water to pass through. Nail polishes with polymer blends that help them withstand or make them more impermeable to water often chip less quickly and stay shinier longer.
While nail polishes are generally deemed safe, newer categories of 3-, 5-, or 8-free nail polishes containing fewer or different ingredients to preserve the product or give it it’s finish have been developed because of health concerns over some ingredients, for both users and cosmetologists. The 8-free nail polish does not contain dibutyl phthalate (DBP), toluene, formaldehyde, formaldehyde resin, camphor, ethyl tosylamide, parabens, or xylene. Three-, 5-, or 8- free doesn’t always mean that the lacquer has fewer chemicals; it may have alternative ingredients that also warrant study comparison to traditional ingredients.
Halal nail polish is in another category of “breathable nail polish,” which is not purely a function of the ingredient or lack of ingredients, but has to do with the way it is formulated. Compared with the tight molecular bonds of traditional nail polish, “breathable” polishes have a more staggered structure, which allows air and water molecules to pass through the polish. Halal nail polish is often free of the same ingredients as 8-free polishes, and some brands are even 13-free, animal product free, and do not require a base or top coat, but may also contain ingredients like bis (glycidoxyphenyl) propane/bisaminomethylnorbornae. Those ingredients are not typically used in traditional nail polish and may play a role in the unique staggered structure allowing air and water to pass through the polish. Halal nail polish may not last as long on nails as does traditional nail polish, usually a few days to a week.
In the past, some Islamic women would not wear nail polish because it is not porous, and so would interfere with wudu or ablution, the Islamic tradition of washing parts of the body before prayer. Halal translates to what is permissible and is most often associated with diet and procuring of meat. While the custom is not the same, the purpose is analogous to kosher preparation of foods in Judaism and dietary traditions in Hinduism. Having the opportunity to learn about this nail polish has been an interesting way to learn more about how different traditions, cultures, and faith affect skin and nail care.
Our nails are circulating breathing structures, with our nail plates being appendages over our nail beds with a rich pulse and blood supply. The main oxygen supply to the ends of our digits comes from our blood supply, not via oxygen through the nail plate, but wearing nail polish continuously can affect our nails. Oxygen saturation is detected through the end of our digits and nails when vital signs are being checked (less so when nail polish is present). As a continual wearer of nail polish for over 30 years, I can personally attest to certain types of onychodystrophy (white spots and discoloration on toe nails) from overuse of dark nail polish colors. Taking a break from polish and using these more “breathable” polishes could also potentially be a solution to this common complaint of nonfungal onychodystrophy.
Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
Ever heard of halal nail polish? As an expert on all things hair, skin, and nails, I was dismayed when I walked into my local nail salon and saw this new category of nail polish I’d never heard of before. About 10 halal nail polishes were available in an array of beautiful colors. This nail salon was already branded as “nontoxic,” carrying only “8-free” nail polishes, vegan, and cruelty-free body and cleaning products – as well as no acrylics or UV light devices used for drying manicured nails or processing gel nails. With the salon already providing 8-free nail polishes, what was the difference between those and halal nail polishes?
As I did my Google search while sitting in the salon chair, I got the answer both from salon employees and the Internet, and also found several other brands of halal nail polishes sold on Amazon.
The main ingredient in traditional nail lacquer is nitrocellulose, a mixture of an indigestible plant fiber. Once used for gunpowder and blast mining in the 19th century, today, nitrocellulose is used for many purposes for holding materials together, such as photography film, and diagnostic tests that involve antigen-antibody binding, such as pregnancy tests. In a bottle of traditional nail polish, nitrocellulose is dissolved in a chemical solvent (typically ethyl acetate), along with pigment colors and plasticizers. The solvent quickly evaporates and is what gives nail polish its chemical smell. Once painted on the nail, the solvent gradually evaporates away entirely and the nitrocellulose is left behind, drying into a solid film on the nail. The same solvent molecule is in nonacetone nail polish remover, which simply redissolves the nitrocellulose back into a liquid so it can be wiped off.
Some nail polish may also include “pearl essence” to give a shiny look, like the silvery iridescence of fish scales. In fact, these polishes have contained ground up iridescent fish scales, but because of overfishing and cost, cheaper mineral alternatives are now more commonly used to give this shiny appearance.
Traditional nail polish contains tight molecular bonds that are impermeable to air and water. The tight bonds create fewer interstitial spaces for water to pass through. Nail polishes with polymer blends that help them withstand or make them more impermeable to water often chip less quickly and stay shinier longer.
While nail polishes are generally deemed safe, newer categories of 3-, 5-, or 8-free nail polishes containing fewer or different ingredients to preserve the product or give it it’s finish have been developed because of health concerns over some ingredients, for both users and cosmetologists. The 8-free nail polish does not contain dibutyl phthalate (DBP), toluene, formaldehyde, formaldehyde resin, camphor, ethyl tosylamide, parabens, or xylene. Three-, 5-, or 8- free doesn’t always mean that the lacquer has fewer chemicals; it may have alternative ingredients that also warrant study comparison to traditional ingredients.
Halal nail polish is in another category of “breathable nail polish,” which is not purely a function of the ingredient or lack of ingredients, but has to do with the way it is formulated. Compared with the tight molecular bonds of traditional nail polish, “breathable” polishes have a more staggered structure, which allows air and water molecules to pass through the polish. Halal nail polish is often free of the same ingredients as 8-free polishes, and some brands are even 13-free, animal product free, and do not require a base or top coat, but may also contain ingredients like bis (glycidoxyphenyl) propane/bisaminomethylnorbornae. Those ingredients are not typically used in traditional nail polish and may play a role in the unique staggered structure allowing air and water to pass through the polish. Halal nail polish may not last as long on nails as does traditional nail polish, usually a few days to a week.
In the past, some Islamic women would not wear nail polish because it is not porous, and so would interfere with wudu or ablution, the Islamic tradition of washing parts of the body before prayer. Halal translates to what is permissible and is most often associated with diet and procuring of meat. While the custom is not the same, the purpose is analogous to kosher preparation of foods in Judaism and dietary traditions in Hinduism. Having the opportunity to learn about this nail polish has been an interesting way to learn more about how different traditions, cultures, and faith affect skin and nail care.
Our nails are circulating breathing structures, with our nail plates being appendages over our nail beds with a rich pulse and blood supply. The main oxygen supply to the ends of our digits comes from our blood supply, not via oxygen through the nail plate, but wearing nail polish continuously can affect our nails. Oxygen saturation is detected through the end of our digits and nails when vital signs are being checked (less so when nail polish is present). As a continual wearer of nail polish for over 30 years, I can personally attest to certain types of onychodystrophy (white spots and discoloration on toe nails) from overuse of dark nail polish colors. Taking a break from polish and using these more “breathable” polishes could also potentially be a solution to this common complaint of nonfungal onychodystrophy.
Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
Ever heard of halal nail polish? As an expert on all things hair, skin, and nails, I was dismayed when I walked into my local nail salon and saw this new category of nail polish I’d never heard of before. About 10 halal nail polishes were available in an array of beautiful colors. This nail salon was already branded as “nontoxic,” carrying only “8-free” nail polishes, vegan, and cruelty-free body and cleaning products – as well as no acrylics or UV light devices used for drying manicured nails or processing gel nails. With the salon already providing 8-free nail polishes, what was the difference between those and halal nail polishes?
As I did my Google search while sitting in the salon chair, I got the answer both from salon employees and the Internet, and also found several other brands of halal nail polishes sold on Amazon.
The main ingredient in traditional nail lacquer is nitrocellulose, a mixture of an indigestible plant fiber. Once used for gunpowder and blast mining in the 19th century, today, nitrocellulose is used for many purposes for holding materials together, such as photography film, and diagnostic tests that involve antigen-antibody binding, such as pregnancy tests. In a bottle of traditional nail polish, nitrocellulose is dissolved in a chemical solvent (typically ethyl acetate), along with pigment colors and plasticizers. The solvent quickly evaporates and is what gives nail polish its chemical smell. Once painted on the nail, the solvent gradually evaporates away entirely and the nitrocellulose is left behind, drying into a solid film on the nail. The same solvent molecule is in nonacetone nail polish remover, which simply redissolves the nitrocellulose back into a liquid so it can be wiped off.
Some nail polish may also include “pearl essence” to give a shiny look, like the silvery iridescence of fish scales. In fact, these polishes have contained ground up iridescent fish scales, but because of overfishing and cost, cheaper mineral alternatives are now more commonly used to give this shiny appearance.
Traditional nail polish contains tight molecular bonds that are impermeable to air and water. The tight bonds create fewer interstitial spaces for water to pass through. Nail polishes with polymer blends that help them withstand or make them more impermeable to water often chip less quickly and stay shinier longer.
While nail polishes are generally deemed safe, newer categories of 3-, 5-, or 8-free nail polishes containing fewer or different ingredients to preserve the product or give it it’s finish have been developed because of health concerns over some ingredients, for both users and cosmetologists. The 8-free nail polish does not contain dibutyl phthalate (DBP), toluene, formaldehyde, formaldehyde resin, camphor, ethyl tosylamide, parabens, or xylene. Three-, 5-, or 8- free doesn’t always mean that the lacquer has fewer chemicals; it may have alternative ingredients that also warrant study comparison to traditional ingredients.
Halal nail polish is in another category of “breathable nail polish,” which is not purely a function of the ingredient or lack of ingredients, but has to do with the way it is formulated. Compared with the tight molecular bonds of traditional nail polish, “breathable” polishes have a more staggered structure, which allows air and water molecules to pass through the polish. Halal nail polish is often free of the same ingredients as 8-free polishes, and some brands are even 13-free, animal product free, and do not require a base or top coat, but may also contain ingredients like bis (glycidoxyphenyl) propane/bisaminomethylnorbornae. Those ingredients are not typically used in traditional nail polish and may play a role in the unique staggered structure allowing air and water to pass through the polish. Halal nail polish may not last as long on nails as does traditional nail polish, usually a few days to a week.
In the past, some Islamic women would not wear nail polish because it is not porous, and so would interfere with wudu or ablution, the Islamic tradition of washing parts of the body before prayer. Halal translates to what is permissible and is most often associated with diet and procuring of meat. While the custom is not the same, the purpose is analogous to kosher preparation of foods in Judaism and dietary traditions in Hinduism. Having the opportunity to learn about this nail polish has been an interesting way to learn more about how different traditions, cultures, and faith affect skin and nail care.
Our nails are circulating breathing structures, with our nail plates being appendages over our nail beds with a rich pulse and blood supply. The main oxygen supply to the ends of our digits comes from our blood supply, not via oxygen through the nail plate, but wearing nail polish continuously can affect our nails. Oxygen saturation is detected through the end of our digits and nails when vital signs are being checked (less so when nail polish is present). As a continual wearer of nail polish for over 30 years, I can personally attest to certain types of onychodystrophy (white spots and discoloration on toe nails) from overuse of dark nail polish colors. Taking a break from polish and using these more “breathable” polishes could also potentially be a solution to this common complaint of nonfungal onychodystrophy.
Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.
Piceatannol: The other potent antioxidant in grapes and wine
Present in grape skins, passion fruit, and wine among several other plants and their derivatives, piceatannol is a natural stilbene, as well as an analogue of the much-studied antioxidant resveratrol. Similarly, piceatannol is thought to provide robust antioxidant and other salutary benefits.1,2
Two decades ago, the hydroxystilbenes piceatannol and transresveratrol were found, in a study of the antioxidant potential of natural products, to hinder carcinogen-induced preneoplastic lesion development in a murine mammary gland organ culture model.3 Piceatannol is naturally present in various plants and is a primary active ingredient in several. It is known to exhibit a wide range of biologic activities, including antioxidant, antibacterial, anti-inflammatory, and anticancer functions. Native to southern and southeastern Asia, Rhodomyrtus tomentosa (rose myrtle, which is a member of the Myrtaceae family), which has been utilized in traditional medicine in China, Malaysia, and Vietnam for myriad indications including wound healing, contains piceatannol as an active ingredient.4
The reported cutaneous benefits of piceatannol include promotion of collagen synthesis, suppression of melanin production, induction of the antioxidant glutathione, and the destruction of reactive oxygen species.5
Antimelanogenic activity
In 2007, Yokozawa and Kim looked into the capacity of piceatannol, given its antioxidant activities, to suppress melanogenesis. This ability was tested using the B16F10 melanoma culture system, and piceatannol was found to have a potent antityrosinase activity – stronger than kojic acid and resveratrol. Melanin content was also down-regulated by piceatannol. In addition, the researchers determined that piceatannol inhibited reactive oxygen species production, which improved the ratio of glutathione to oxidized glutathione. They concluded that the observed antimelanogenic activities of piceatannol could be attributed to its dynamic antioxidant qualities.6
Four years later, Matsui et al. ascertained that piceatannol (3,4,3’,5’-tetrahydroxy-trans-stilbene) is present in copious supply in the seeds of Passiflora edulis (passion fruit) and that this constituent of the fruit largely accounts for its antimelanogenic activities, as well as its promotion of collagen production.7
Anti-inflammatory activity
In 2014, Liu et al. used female HR-1 hairless mice in a study to shed light on the molecular mechanisms of the anti-inflammatory activity of topically applied piceatannol in vivo. Mice, either pretreated with piceatannol or not, were topically treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and pretreatment was found to yield diminished TPA-induced cyclooxygenase-2 (COX-2) expression and inducible nitric oxide synthase (iNOS). This occurred through the suppression of NF-kappa-B and AP-1 activation as a result of hindering IKK-beta activity and phosphorylation of mitogen-activated protein kinases.8
Photoprotection
Maruki-Uchida et al. studied the effects of the antioxidants piceatannol and its dimer scirpusin B, which is found in passion fruit, on human keratinocytes. In this 2013 study, they found that piceatannol dose-dependently up-regulated glutathione levels. In addition, piceatannol pretreatment blocked UVB-induced reactive oxygen species development. Pretreatment with piceatannol also reduced matrix metalloproteinase-1 activity in a nonirradiated medium of fibroblasts. The investigators concluded that piceatannol and piceatannol-rich passion fruit seed extract warrant attention as possible antiphotoaging cosmetic agents.9
With use of cultured normal human epidermal keratinocytes, Shiratake et al. in 2015 screened more than 50 plant extracts for ingredients that hinder UVB-induced damage. They identified the fruit R. tomentosa as the strongest inhibitor, with its primary component, piceatannol, demonstrating protective activities against UVB. Piceatannol decreased UVB-induced cyclobutane pyrimidine dimer synthesis, diminished prostaglandin E2 secretion, and promoted the cellular enzyme activity of DNA polymerases. The investigators concluded that rose myrtle extracts and piceatannol are potential photoprotective agents.10
Dry skin
In a 2018 randomized, placebo-controlled, double-blind trial Maruki-Uchida et al. assessed the effects of passion fruit seed extract on the skin of 32 healthy Japanese women (aged 35-54 years). Over an 8-week period, the subjects, all with dry skin, received either 5 mg of piceatannol (derived from passion fruit seed extract) or a dextrin placebo. Significant increases in cutaneous moisture content were noted in the subjects who consumed passion fruit after 4 and 8 weeks, compared with baseline and with the placebo group. Questionnaire results also indicated that perspiration and fatigue significantly decreased in the passion fruit group as compared with the placebo group. The researchers concluded that consumption of piceatannol-rich passion fruit seed extract can ameliorate dry skin and diminish fatigue.5
Conclusion
Although it gets much less attention than the related antioxidant resveratrol, piceatannol is hardly an insignificant bioactive compound. There is increasing evidence that suggests its potency as an antioxidant, as well as a potentially useful ingredient in skincare, particularly in addressing photoaging and dry skin. Much more research is necessary, of course, to determine how substantial a role this stilbene can play in providing skin protection and treatment.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), as well as a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Phytother Res. 2014 Nov;28(11):1581-8.
2. Biogerontology. 2017 Aug;18(4):499-516.
3. Comb Chem High Throughput Screen. 1998 Apr;1(1):35-46.
4. Biomolecules. 2019 Feb 21. doi: 10.3390/biom9020076.
5. J Nutr Sci Vitaminol (Tokyo). 2018;64(1):75-80.
6. Biol Pharm Bull. 2007 Nov;30(11):2007-11.
7. J Agric Food Chem. 2010 Oct 27;58(20):11112-8.
8. Inflamm Res. 2014 Dec;63(12):1013-21.
9. Biol Pharm Bull. 2013;36(5):845-9.
10. Mol Med Rep. 2015 Oct;12(4):5857-64.
Present in grape skins, passion fruit, and wine among several other plants and their derivatives, piceatannol is a natural stilbene, as well as an analogue of the much-studied antioxidant resveratrol. Similarly, piceatannol is thought to provide robust antioxidant and other salutary benefits.1,2
Two decades ago, the hydroxystilbenes piceatannol and transresveratrol were found, in a study of the antioxidant potential of natural products, to hinder carcinogen-induced preneoplastic lesion development in a murine mammary gland organ culture model.3 Piceatannol is naturally present in various plants and is a primary active ingredient in several. It is known to exhibit a wide range of biologic activities, including antioxidant, antibacterial, anti-inflammatory, and anticancer functions. Native to southern and southeastern Asia, Rhodomyrtus tomentosa (rose myrtle, which is a member of the Myrtaceae family), which has been utilized in traditional medicine in China, Malaysia, and Vietnam for myriad indications including wound healing, contains piceatannol as an active ingredient.4
The reported cutaneous benefits of piceatannol include promotion of collagen synthesis, suppression of melanin production, induction of the antioxidant glutathione, and the destruction of reactive oxygen species.5
Antimelanogenic activity
In 2007, Yokozawa and Kim looked into the capacity of piceatannol, given its antioxidant activities, to suppress melanogenesis. This ability was tested using the B16F10 melanoma culture system, and piceatannol was found to have a potent antityrosinase activity – stronger than kojic acid and resveratrol. Melanin content was also down-regulated by piceatannol. In addition, the researchers determined that piceatannol inhibited reactive oxygen species production, which improved the ratio of glutathione to oxidized glutathione. They concluded that the observed antimelanogenic activities of piceatannol could be attributed to its dynamic antioxidant qualities.6
Four years later, Matsui et al. ascertained that piceatannol (3,4,3’,5’-tetrahydroxy-trans-stilbene) is present in copious supply in the seeds of Passiflora edulis (passion fruit) and that this constituent of the fruit largely accounts for its antimelanogenic activities, as well as its promotion of collagen production.7
Anti-inflammatory activity
In 2014, Liu et al. used female HR-1 hairless mice in a study to shed light on the molecular mechanisms of the anti-inflammatory activity of topically applied piceatannol in vivo. Mice, either pretreated with piceatannol or not, were topically treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and pretreatment was found to yield diminished TPA-induced cyclooxygenase-2 (COX-2) expression and inducible nitric oxide synthase (iNOS). This occurred through the suppression of NF-kappa-B and AP-1 activation as a result of hindering IKK-beta activity and phosphorylation of mitogen-activated protein kinases.8
Photoprotection
Maruki-Uchida et al. studied the effects of the antioxidants piceatannol and its dimer scirpusin B, which is found in passion fruit, on human keratinocytes. In this 2013 study, they found that piceatannol dose-dependently up-regulated glutathione levels. In addition, piceatannol pretreatment blocked UVB-induced reactive oxygen species development. Pretreatment with piceatannol also reduced matrix metalloproteinase-1 activity in a nonirradiated medium of fibroblasts. The investigators concluded that piceatannol and piceatannol-rich passion fruit seed extract warrant attention as possible antiphotoaging cosmetic agents.9
With use of cultured normal human epidermal keratinocytes, Shiratake et al. in 2015 screened more than 50 plant extracts for ingredients that hinder UVB-induced damage. They identified the fruit R. tomentosa as the strongest inhibitor, with its primary component, piceatannol, demonstrating protective activities against UVB. Piceatannol decreased UVB-induced cyclobutane pyrimidine dimer synthesis, diminished prostaglandin E2 secretion, and promoted the cellular enzyme activity of DNA polymerases. The investigators concluded that rose myrtle extracts and piceatannol are potential photoprotective agents.10
Dry skin
In a 2018 randomized, placebo-controlled, double-blind trial Maruki-Uchida et al. assessed the effects of passion fruit seed extract on the skin of 32 healthy Japanese women (aged 35-54 years). Over an 8-week period, the subjects, all with dry skin, received either 5 mg of piceatannol (derived from passion fruit seed extract) or a dextrin placebo. Significant increases in cutaneous moisture content were noted in the subjects who consumed passion fruit after 4 and 8 weeks, compared with baseline and with the placebo group. Questionnaire results also indicated that perspiration and fatigue significantly decreased in the passion fruit group as compared with the placebo group. The researchers concluded that consumption of piceatannol-rich passion fruit seed extract can ameliorate dry skin and diminish fatigue.5
Conclusion
Although it gets much less attention than the related antioxidant resveratrol, piceatannol is hardly an insignificant bioactive compound. There is increasing evidence that suggests its potency as an antioxidant, as well as a potentially useful ingredient in skincare, particularly in addressing photoaging and dry skin. Much more research is necessary, of course, to determine how substantial a role this stilbene can play in providing skin protection and treatment.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), as well as a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Phytother Res. 2014 Nov;28(11):1581-8.
2. Biogerontology. 2017 Aug;18(4):499-516.
3. Comb Chem High Throughput Screen. 1998 Apr;1(1):35-46.
4. Biomolecules. 2019 Feb 21. doi: 10.3390/biom9020076.
5. J Nutr Sci Vitaminol (Tokyo). 2018;64(1):75-80.
6. Biol Pharm Bull. 2007 Nov;30(11):2007-11.
7. J Agric Food Chem. 2010 Oct 27;58(20):11112-8.
8. Inflamm Res. 2014 Dec;63(12):1013-21.
9. Biol Pharm Bull. 2013;36(5):845-9.
10. Mol Med Rep. 2015 Oct;12(4):5857-64.
Present in grape skins, passion fruit, and wine among several other plants and their derivatives, piceatannol is a natural stilbene, as well as an analogue of the much-studied antioxidant resveratrol. Similarly, piceatannol is thought to provide robust antioxidant and other salutary benefits.1,2
Two decades ago, the hydroxystilbenes piceatannol and transresveratrol were found, in a study of the antioxidant potential of natural products, to hinder carcinogen-induced preneoplastic lesion development in a murine mammary gland organ culture model.3 Piceatannol is naturally present in various plants and is a primary active ingredient in several. It is known to exhibit a wide range of biologic activities, including antioxidant, antibacterial, anti-inflammatory, and anticancer functions. Native to southern and southeastern Asia, Rhodomyrtus tomentosa (rose myrtle, which is a member of the Myrtaceae family), which has been utilized in traditional medicine in China, Malaysia, and Vietnam for myriad indications including wound healing, contains piceatannol as an active ingredient.4
The reported cutaneous benefits of piceatannol include promotion of collagen synthesis, suppression of melanin production, induction of the antioxidant glutathione, and the destruction of reactive oxygen species.5
Antimelanogenic activity
In 2007, Yokozawa and Kim looked into the capacity of piceatannol, given its antioxidant activities, to suppress melanogenesis. This ability was tested using the B16F10 melanoma culture system, and piceatannol was found to have a potent antityrosinase activity – stronger than kojic acid and resveratrol. Melanin content was also down-regulated by piceatannol. In addition, the researchers determined that piceatannol inhibited reactive oxygen species production, which improved the ratio of glutathione to oxidized glutathione. They concluded that the observed antimelanogenic activities of piceatannol could be attributed to its dynamic antioxidant qualities.6
Four years later, Matsui et al. ascertained that piceatannol (3,4,3’,5’-tetrahydroxy-trans-stilbene) is present in copious supply in the seeds of Passiflora edulis (passion fruit) and that this constituent of the fruit largely accounts for its antimelanogenic activities, as well as its promotion of collagen production.7
Anti-inflammatory activity
In 2014, Liu et al. used female HR-1 hairless mice in a study to shed light on the molecular mechanisms of the anti-inflammatory activity of topically applied piceatannol in vivo. Mice, either pretreated with piceatannol or not, were topically treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and pretreatment was found to yield diminished TPA-induced cyclooxygenase-2 (COX-2) expression and inducible nitric oxide synthase (iNOS). This occurred through the suppression of NF-kappa-B and AP-1 activation as a result of hindering IKK-beta activity and phosphorylation of mitogen-activated protein kinases.8
Photoprotection
Maruki-Uchida et al. studied the effects of the antioxidants piceatannol and its dimer scirpusin B, which is found in passion fruit, on human keratinocytes. In this 2013 study, they found that piceatannol dose-dependently up-regulated glutathione levels. In addition, piceatannol pretreatment blocked UVB-induced reactive oxygen species development. Pretreatment with piceatannol also reduced matrix metalloproteinase-1 activity in a nonirradiated medium of fibroblasts. The investigators concluded that piceatannol and piceatannol-rich passion fruit seed extract warrant attention as possible antiphotoaging cosmetic agents.9
With use of cultured normal human epidermal keratinocytes, Shiratake et al. in 2015 screened more than 50 plant extracts for ingredients that hinder UVB-induced damage. They identified the fruit R. tomentosa as the strongest inhibitor, with its primary component, piceatannol, demonstrating protective activities against UVB. Piceatannol decreased UVB-induced cyclobutane pyrimidine dimer synthesis, diminished prostaglandin E2 secretion, and promoted the cellular enzyme activity of DNA polymerases. The investigators concluded that rose myrtle extracts and piceatannol are potential photoprotective agents.10
Dry skin
In a 2018 randomized, placebo-controlled, double-blind trial Maruki-Uchida et al. assessed the effects of passion fruit seed extract on the skin of 32 healthy Japanese women (aged 35-54 years). Over an 8-week period, the subjects, all with dry skin, received either 5 mg of piceatannol (derived from passion fruit seed extract) or a dextrin placebo. Significant increases in cutaneous moisture content were noted in the subjects who consumed passion fruit after 4 and 8 weeks, compared with baseline and with the placebo group. Questionnaire results also indicated that perspiration and fatigue significantly decreased in the passion fruit group as compared with the placebo group. The researchers concluded that consumption of piceatannol-rich passion fruit seed extract can ameliorate dry skin and diminish fatigue.5
Conclusion
Although it gets much less attention than the related antioxidant resveratrol, piceatannol is hardly an insignificant bioactive compound. There is increasing evidence that suggests its potency as an antioxidant, as well as a potentially useful ingredient in skincare, particularly in addressing photoaging and dry skin. Much more research is necessary, of course, to determine how substantial a role this stilbene can play in providing skin protection and treatment.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), as well as a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].
References
1. Phytother Res. 2014 Nov;28(11):1581-8.
2. Biogerontology. 2017 Aug;18(4):499-516.
3. Comb Chem High Throughput Screen. 1998 Apr;1(1):35-46.
4. Biomolecules. 2019 Feb 21. doi: 10.3390/biom9020076.
5. J Nutr Sci Vitaminol (Tokyo). 2018;64(1):75-80.
6. Biol Pharm Bull. 2007 Nov;30(11):2007-11.
7. J Agric Food Chem. 2010 Oct 27;58(20):11112-8.
8. Inflamm Res. 2014 Dec;63(12):1013-21.
9. Biol Pharm Bull. 2013;36(5):845-9.
10. Mol Med Rep. 2015 Oct;12(4):5857-64.
FDA panel supports Vascepa expanded indication for CVD reduction
Icosapent ethyl, a highly purified form of the ethyl ester of eicosapentaenoic acid, received unanimous backing from a Food and Drug Administration advisory panel for a new indication for reducing cardiovascular event risk.
Icosapent ethyl (Vascepa) received initial agency approval in 2012 for the indication of cutting triglyceride levels once they reached at least 500 mg/dL.
The target patient population for this new, cardiovascular-event protection role will reflect some or all of the types of patients enrolled in REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), which tested icosapent ethyl in 8,179 patients with either established cardiovascular disease or diabetes and at least one additional cardiovascular disease risk factor. This study provided the bulk of the data considered by the FDA panel.
REDUCE-IT showed that, during a median of 4.9 years, patients who received icosapent ethyl had a statistically significant 25% relative risk reduction in the trial’s primary, composite endpoint (New Engl J Med. 2019 Jan 3;380[1]:11-22).
Icosapent ethyl “appeared effective and safe,” and would be a “useful, new, added agent for treating patients” like those enrolled in the trial, said Kenneth D. Burman, MD, professor and chief of endocrinology at Medstar Washington (D.C.) Hospital Center and chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
The advisory panel members appeared uniformly comfortable with recommending that the FDA add a cardiovascular disease indication based on the REDUCE-IT findings.
But while they agreed that icosapent ethyl should receive some type of indication for cardiovascular event reduction, the committee split over which patients the indication should include. Specifically, they diverged on the issue of primary prevention.
Some said that the patient enrollment that produced a positive result in REDUCE-IT should not be retrospectively subdivided, while others said that combining secondary- and primary-prevention patients in a single large trial inappropriately lumped together patients who would be better considered separately.
Committee members also expressed uncertainty over the appropriate triglyceride level to warrant treatment. The REDUCE-IT trial was designed to enroll patients with triglycerides of 135 mg/dL or greater, but several panel members suggested that, for labeling, the threshold should be at least 150 mg/dL, or even 200 mg/dL.
Safety was another aspect that generated a lot of panel discussion throughout their day-long discussion, with particular focus on a signal of a small but concerning increased rate of incident atrial fibrillation among patients who received icosapent ethyl, as well as a small but nearly significant increase in the rate of serious bleeds.
Further analyses presented during the meeting showed that an increased bleeding rate linked with icosapent ethyl was focused in patients who concurrently received one or more antiplatelet drugs or an anticoagulant.
However, panel members rejected the notion that these safety concerns warranted a boxed warning, agreeing that it could be managed with appropriate labeling information.
Clinician reaction
Clinicians who manage these types of patients viewed the prospect of an expanded indication for icosapent ethyl as an important advance.
The REDUCE-IT results by themselves “were convincing” for patients with established cardiovascular disease without need for a confirmatory trial, Robert H. Eckel, MD, an endocrinologist and professor of medicine at the University of Colorado at Denver, Aurora, said in an interview. But he remained unconvinced about efficacy for primary-prevention patients, or even for secondary-prevention patients with a triglyceride level below 150 mg/dL.
“Icosapent ethyl will clearly be a mainstay for managing high-risk patients. It gives us another treatment option,” Yehuda Handelsman, MD, an endocrinologist and medical director and principal investigator of the Metabolic Institute of America in Tarzana, Calif., said in an interview. “I do not see the atrial fibrillation or bleeding effects as reasons not to approve this drug. It should be a precaution. Overall, icosapent ethyl is one of the easier drugs for patients to take.”
Dr. Handelsman said it would be unethical to run a confirmatory trial and randomize patients to placebo. “Another trial makes no sense,” he said.
But the data from REDUCE-IT were “not as convincing” for primary-prevention patients, suggesting a need for caution about using icosapent ethyl for patients without established cardiovascular disease, Paul S. Jellinger, MD, an endocrinologist in Fort Lauderdale, Fla., said in an interview.
Cost-effectiveness
An analysis of the cost-effectiveness of icosapent ethyl as used in REDUCE-IT showed that the drug fell into the rare category of being a “dominant” treatment, meaning that it both improved patient outcomes and reduced medical costs. William S. Weintraub, MD, will report findings from this analysis on Nov. 16, 2019, at the annual scientific sessions of the American Heart Association.
The analysis used a wholesale acquisition cost for a 1-day dosage of icosapent ethyl of $4.16, derived from a commercial source for prescription-drug pricing and actual hospitalization costs for the patients in the trial.
Based on the REDUCE-IT outcomes, treatment with icosapent ethyl was linked with a boost in quality-adjusted life-years that extrapolated to an average 0.26 increase during the full lifetime of REDUCE-IT participants, at a cost that averaged $1,284 less per treated patient over their lifetime, according to Dr. Weintraub, director of Outcomes Research at Medstar Washington Hospital Center, Washington.
Although the 0.26 lifetime increase in quality-adjusted life-years may sound modest, “in the cost-effectiveness world, 0.26 is actually significant,” Dr. Weintraub said. He also highlighted how unusual it is to find a patented drug that improves quality of life and longevity while also saving money.
“I know of no other on-patent, branded pharmaceutical that is dominant,” he said.
Off-patent pharmaceuticals, like statins, can be quite inexpensive and may also be dominant, he noted. Being dominant for cost-effectiveness means that icosapent ethyl “provides good value and is worth what we pay for it, well within social thresholds of willingness to pay,” Dr. Weintraub said.
REDUCE-IT was sponsored by Amarin, the company that markets icosapent ethyl (Vascepa). Dr. Burman has received research funding from AstraZeneca, Eisai, and IBSA. Dr. Eckel has received personal fees from Kowa Pharmaceuticals, Merck, Novartis, and Sanofi/Regeneron, as well as research funding from Endece, Ionis Pharmaceuticals, and UniQure. Dr. Handelsman has been a consultant to and received research funding from Amarin and several other companies. Dr. Jellinger has been a speaker on behalf of Amarin, Amgen, and Regeneron. Dr. Weintraub has received honoraria and research support from Amarin, and honoraria from AstraZeneca.
Icosapent ethyl, a highly purified form of the ethyl ester of eicosapentaenoic acid, received unanimous backing from a Food and Drug Administration advisory panel for a new indication for reducing cardiovascular event risk.
Icosapent ethyl (Vascepa) received initial agency approval in 2012 for the indication of cutting triglyceride levels once they reached at least 500 mg/dL.
The target patient population for this new, cardiovascular-event protection role will reflect some or all of the types of patients enrolled in REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), which tested icosapent ethyl in 8,179 patients with either established cardiovascular disease or diabetes and at least one additional cardiovascular disease risk factor. This study provided the bulk of the data considered by the FDA panel.
REDUCE-IT showed that, during a median of 4.9 years, patients who received icosapent ethyl had a statistically significant 25% relative risk reduction in the trial’s primary, composite endpoint (New Engl J Med. 2019 Jan 3;380[1]:11-22).
Icosapent ethyl “appeared effective and safe,” and would be a “useful, new, added agent for treating patients” like those enrolled in the trial, said Kenneth D. Burman, MD, professor and chief of endocrinology at Medstar Washington (D.C.) Hospital Center and chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
The advisory panel members appeared uniformly comfortable with recommending that the FDA add a cardiovascular disease indication based on the REDUCE-IT findings.
But while they agreed that icosapent ethyl should receive some type of indication for cardiovascular event reduction, the committee split over which patients the indication should include. Specifically, they diverged on the issue of primary prevention.
Some said that the patient enrollment that produced a positive result in REDUCE-IT should not be retrospectively subdivided, while others said that combining secondary- and primary-prevention patients in a single large trial inappropriately lumped together patients who would be better considered separately.
Committee members also expressed uncertainty over the appropriate triglyceride level to warrant treatment. The REDUCE-IT trial was designed to enroll patients with triglycerides of 135 mg/dL or greater, but several panel members suggested that, for labeling, the threshold should be at least 150 mg/dL, or even 200 mg/dL.
Safety was another aspect that generated a lot of panel discussion throughout their day-long discussion, with particular focus on a signal of a small but concerning increased rate of incident atrial fibrillation among patients who received icosapent ethyl, as well as a small but nearly significant increase in the rate of serious bleeds.
Further analyses presented during the meeting showed that an increased bleeding rate linked with icosapent ethyl was focused in patients who concurrently received one or more antiplatelet drugs or an anticoagulant.
However, panel members rejected the notion that these safety concerns warranted a boxed warning, agreeing that it could be managed with appropriate labeling information.
Clinician reaction
Clinicians who manage these types of patients viewed the prospect of an expanded indication for icosapent ethyl as an important advance.
The REDUCE-IT results by themselves “were convincing” for patients with established cardiovascular disease without need for a confirmatory trial, Robert H. Eckel, MD, an endocrinologist and professor of medicine at the University of Colorado at Denver, Aurora, said in an interview. But he remained unconvinced about efficacy for primary-prevention patients, or even for secondary-prevention patients with a triglyceride level below 150 mg/dL.
“Icosapent ethyl will clearly be a mainstay for managing high-risk patients. It gives us another treatment option,” Yehuda Handelsman, MD, an endocrinologist and medical director and principal investigator of the Metabolic Institute of America in Tarzana, Calif., said in an interview. “I do not see the atrial fibrillation or bleeding effects as reasons not to approve this drug. It should be a precaution. Overall, icosapent ethyl is one of the easier drugs for patients to take.”
Dr. Handelsman said it would be unethical to run a confirmatory trial and randomize patients to placebo. “Another trial makes no sense,” he said.
But the data from REDUCE-IT were “not as convincing” for primary-prevention patients, suggesting a need for caution about using icosapent ethyl for patients without established cardiovascular disease, Paul S. Jellinger, MD, an endocrinologist in Fort Lauderdale, Fla., said in an interview.
Cost-effectiveness
An analysis of the cost-effectiveness of icosapent ethyl as used in REDUCE-IT showed that the drug fell into the rare category of being a “dominant” treatment, meaning that it both improved patient outcomes and reduced medical costs. William S. Weintraub, MD, will report findings from this analysis on Nov. 16, 2019, at the annual scientific sessions of the American Heart Association.
The analysis used a wholesale acquisition cost for a 1-day dosage of icosapent ethyl of $4.16, derived from a commercial source for prescription-drug pricing and actual hospitalization costs for the patients in the trial.
Based on the REDUCE-IT outcomes, treatment with icosapent ethyl was linked with a boost in quality-adjusted life-years that extrapolated to an average 0.26 increase during the full lifetime of REDUCE-IT participants, at a cost that averaged $1,284 less per treated patient over their lifetime, according to Dr. Weintraub, director of Outcomes Research at Medstar Washington Hospital Center, Washington.
Although the 0.26 lifetime increase in quality-adjusted life-years may sound modest, “in the cost-effectiveness world, 0.26 is actually significant,” Dr. Weintraub said. He also highlighted how unusual it is to find a patented drug that improves quality of life and longevity while also saving money.
“I know of no other on-patent, branded pharmaceutical that is dominant,” he said.
Off-patent pharmaceuticals, like statins, can be quite inexpensive and may also be dominant, he noted. Being dominant for cost-effectiveness means that icosapent ethyl “provides good value and is worth what we pay for it, well within social thresholds of willingness to pay,” Dr. Weintraub said.
REDUCE-IT was sponsored by Amarin, the company that markets icosapent ethyl (Vascepa). Dr. Burman has received research funding from AstraZeneca, Eisai, and IBSA. Dr. Eckel has received personal fees from Kowa Pharmaceuticals, Merck, Novartis, and Sanofi/Regeneron, as well as research funding from Endece, Ionis Pharmaceuticals, and UniQure. Dr. Handelsman has been a consultant to and received research funding from Amarin and several other companies. Dr. Jellinger has been a speaker on behalf of Amarin, Amgen, and Regeneron. Dr. Weintraub has received honoraria and research support from Amarin, and honoraria from AstraZeneca.
Icosapent ethyl, a highly purified form of the ethyl ester of eicosapentaenoic acid, received unanimous backing from a Food and Drug Administration advisory panel for a new indication for reducing cardiovascular event risk.
Icosapent ethyl (Vascepa) received initial agency approval in 2012 for the indication of cutting triglyceride levels once they reached at least 500 mg/dL.
The target patient population for this new, cardiovascular-event protection role will reflect some or all of the types of patients enrolled in REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), which tested icosapent ethyl in 8,179 patients with either established cardiovascular disease or diabetes and at least one additional cardiovascular disease risk factor. This study provided the bulk of the data considered by the FDA panel.
REDUCE-IT showed that, during a median of 4.9 years, patients who received icosapent ethyl had a statistically significant 25% relative risk reduction in the trial’s primary, composite endpoint (New Engl J Med. 2019 Jan 3;380[1]:11-22).
Icosapent ethyl “appeared effective and safe,” and would be a “useful, new, added agent for treating patients” like those enrolled in the trial, said Kenneth D. Burman, MD, professor and chief of endocrinology at Medstar Washington (D.C.) Hospital Center and chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
The advisory panel members appeared uniformly comfortable with recommending that the FDA add a cardiovascular disease indication based on the REDUCE-IT findings.
But while they agreed that icosapent ethyl should receive some type of indication for cardiovascular event reduction, the committee split over which patients the indication should include. Specifically, they diverged on the issue of primary prevention.
Some said that the patient enrollment that produced a positive result in REDUCE-IT should not be retrospectively subdivided, while others said that combining secondary- and primary-prevention patients in a single large trial inappropriately lumped together patients who would be better considered separately.
Committee members also expressed uncertainty over the appropriate triglyceride level to warrant treatment. The REDUCE-IT trial was designed to enroll patients with triglycerides of 135 mg/dL or greater, but several panel members suggested that, for labeling, the threshold should be at least 150 mg/dL, or even 200 mg/dL.
Safety was another aspect that generated a lot of panel discussion throughout their day-long discussion, with particular focus on a signal of a small but concerning increased rate of incident atrial fibrillation among patients who received icosapent ethyl, as well as a small but nearly significant increase in the rate of serious bleeds.
Further analyses presented during the meeting showed that an increased bleeding rate linked with icosapent ethyl was focused in patients who concurrently received one or more antiplatelet drugs or an anticoagulant.
However, panel members rejected the notion that these safety concerns warranted a boxed warning, agreeing that it could be managed with appropriate labeling information.
Clinician reaction
Clinicians who manage these types of patients viewed the prospect of an expanded indication for icosapent ethyl as an important advance.
The REDUCE-IT results by themselves “were convincing” for patients with established cardiovascular disease without need for a confirmatory trial, Robert H. Eckel, MD, an endocrinologist and professor of medicine at the University of Colorado at Denver, Aurora, said in an interview. But he remained unconvinced about efficacy for primary-prevention patients, or even for secondary-prevention patients with a triglyceride level below 150 mg/dL.
“Icosapent ethyl will clearly be a mainstay for managing high-risk patients. It gives us another treatment option,” Yehuda Handelsman, MD, an endocrinologist and medical director and principal investigator of the Metabolic Institute of America in Tarzana, Calif., said in an interview. “I do not see the atrial fibrillation or bleeding effects as reasons not to approve this drug. It should be a precaution. Overall, icosapent ethyl is one of the easier drugs for patients to take.”
Dr. Handelsman said it would be unethical to run a confirmatory trial and randomize patients to placebo. “Another trial makes no sense,” he said.
But the data from REDUCE-IT were “not as convincing” for primary-prevention patients, suggesting a need for caution about using icosapent ethyl for patients without established cardiovascular disease, Paul S. Jellinger, MD, an endocrinologist in Fort Lauderdale, Fla., said in an interview.
Cost-effectiveness
An analysis of the cost-effectiveness of icosapent ethyl as used in REDUCE-IT showed that the drug fell into the rare category of being a “dominant” treatment, meaning that it both improved patient outcomes and reduced medical costs. William S. Weintraub, MD, will report findings from this analysis on Nov. 16, 2019, at the annual scientific sessions of the American Heart Association.
The analysis used a wholesale acquisition cost for a 1-day dosage of icosapent ethyl of $4.16, derived from a commercial source for prescription-drug pricing and actual hospitalization costs for the patients in the trial.
Based on the REDUCE-IT outcomes, treatment with icosapent ethyl was linked with a boost in quality-adjusted life-years that extrapolated to an average 0.26 increase during the full lifetime of REDUCE-IT participants, at a cost that averaged $1,284 less per treated patient over their lifetime, according to Dr. Weintraub, director of Outcomes Research at Medstar Washington Hospital Center, Washington.
Although the 0.26 lifetime increase in quality-adjusted life-years may sound modest, “in the cost-effectiveness world, 0.26 is actually significant,” Dr. Weintraub said. He also highlighted how unusual it is to find a patented drug that improves quality of life and longevity while also saving money.
“I know of no other on-patent, branded pharmaceutical that is dominant,” he said.
Off-patent pharmaceuticals, like statins, can be quite inexpensive and may also be dominant, he noted. Being dominant for cost-effectiveness means that icosapent ethyl “provides good value and is worth what we pay for it, well within social thresholds of willingness to pay,” Dr. Weintraub said.
REDUCE-IT was sponsored by Amarin, the company that markets icosapent ethyl (Vascepa). Dr. Burman has received research funding from AstraZeneca, Eisai, and IBSA. Dr. Eckel has received personal fees from Kowa Pharmaceuticals, Merck, Novartis, and Sanofi/Regeneron, as well as research funding from Endece, Ionis Pharmaceuticals, and UniQure. Dr. Handelsman has been a consultant to and received research funding from Amarin and several other companies. Dr. Jellinger has been a speaker on behalf of Amarin, Amgen, and Regeneron. Dr. Weintraub has received honoraria and research support from Amarin, and honoraria from AstraZeneca.
Lay press stories about research: Putting them into perspective for patients
I recently had an unusual patient call. A woman I’ve seen for many years for migraines called to tell me her son was being hospitalized for appendicitis. He was scheduled for surgery in the morning.
She called because she’d recently seen a news report about how people without an appendix may have a higher rate of Parkinson’s disease as they age. She was, understandably, concerned about the long-term risks the procedure could pose.
On the surface, as a medical professional, the call sounds frivolous and silly. The risks of untreated acute appendicitis, such as peritonitis and death, are pretty well documented. Surgery offers the best possibility for a cure without recurrence. Compared with the long-term, uncertain, risk of Parkinson’s disease, the benefit-to-risk ratio and options are pretty obvious.
The question of the GI tract’s involvement in neurologic diseases is a legitimate one that needs to be answered. It may provide new insight into their causes and potential treatments. The research she brought up raises some interesting points.
But that doesn’t mean there should be any delay in treating something as easily cured – and potentially serious – as acute appendicitis.
My patient called to ask questions, and I have no issue with that. To someone with no medical training, it’s a legitimate concern. But not everyone will call to ask.
This is a hazard of early stages of medical research making it into the lay press. It may be right, it may be wrong, but it’s too early to tell either way. We have years of training to help us recognize the uncertainties of preliminary data, but the general public doesn’t. Stories like this create interest and raise questions in the medical literature and fear and anxiety in the lay press.
I’m a strong supporter of freedom of the press, and certainly they have every right to air or publish such stories. But they should also be put in perspective at the beginning, not the bottom, and make it clear the findings are far from proven.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I recently had an unusual patient call. A woman I’ve seen for many years for migraines called to tell me her son was being hospitalized for appendicitis. He was scheduled for surgery in the morning.
She called because she’d recently seen a news report about how people without an appendix may have a higher rate of Parkinson’s disease as they age. She was, understandably, concerned about the long-term risks the procedure could pose.
On the surface, as a medical professional, the call sounds frivolous and silly. The risks of untreated acute appendicitis, such as peritonitis and death, are pretty well documented. Surgery offers the best possibility for a cure without recurrence. Compared with the long-term, uncertain, risk of Parkinson’s disease, the benefit-to-risk ratio and options are pretty obvious.
The question of the GI tract’s involvement in neurologic diseases is a legitimate one that needs to be answered. It may provide new insight into their causes and potential treatments. The research she brought up raises some interesting points.
But that doesn’t mean there should be any delay in treating something as easily cured – and potentially serious – as acute appendicitis.
My patient called to ask questions, and I have no issue with that. To someone with no medical training, it’s a legitimate concern. But not everyone will call to ask.
This is a hazard of early stages of medical research making it into the lay press. It may be right, it may be wrong, but it’s too early to tell either way. We have years of training to help us recognize the uncertainties of preliminary data, but the general public doesn’t. Stories like this create interest and raise questions in the medical literature and fear and anxiety in the lay press.
I’m a strong supporter of freedom of the press, and certainly they have every right to air or publish such stories. But they should also be put in perspective at the beginning, not the bottom, and make it clear the findings are far from proven.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I recently had an unusual patient call. A woman I’ve seen for many years for migraines called to tell me her son was being hospitalized for appendicitis. He was scheduled for surgery in the morning.
She called because she’d recently seen a news report about how people without an appendix may have a higher rate of Parkinson’s disease as they age. She was, understandably, concerned about the long-term risks the procedure could pose.
On the surface, as a medical professional, the call sounds frivolous and silly. The risks of untreated acute appendicitis, such as peritonitis and death, are pretty well documented. Surgery offers the best possibility for a cure without recurrence. Compared with the long-term, uncertain, risk of Parkinson’s disease, the benefit-to-risk ratio and options are pretty obvious.
The question of the GI tract’s involvement in neurologic diseases is a legitimate one that needs to be answered. It may provide new insight into their causes and potential treatments. The research she brought up raises some interesting points.
But that doesn’t mean there should be any delay in treating something as easily cured – and potentially serious – as acute appendicitis.
My patient called to ask questions, and I have no issue with that. To someone with no medical training, it’s a legitimate concern. But not everyone will call to ask.
This is a hazard of early stages of medical research making it into the lay press. It may be right, it may be wrong, but it’s too early to tell either way. We have years of training to help us recognize the uncertainties of preliminary data, but the general public doesn’t. Stories like this create interest and raise questions in the medical literature and fear and anxiety in the lay press.
I’m a strong supporter of freedom of the press, and certainly they have every right to air or publish such stories. But they should also be put in perspective at the beginning, not the bottom, and make it clear the findings are far from proven.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Venous Venous Venous @VEITHsymposium
The Venous Venous Venous @VEITHsymposium program has become a popular staple of the the VEITHsymposium. Now in its 13th year, the Venous Venous Venous program, which will be held on Wednesday, Thursday, and Friday, features a mixture of didactic sessions and workshops to cover the full gamut of venous disorders and their treatments, surgical, endovascular, and medical. It is “considered to be the best and most complete program,” on venous diseases according to conference organizers.
The didactic Program I (Sessions 63-70) on Superficial Venous Disease will be held all day Thursday and will detail the latest developments in venous clinical examinations and imaging, superficial vein strategies and techniques, thermal and non-thermal ablation, and there will be a special session on venous societal issues and governance.
Moderated by Kathleen J. Ozsvath, MD, and Harold J. Welch, MD, this special program will feature discussions on the future of venous reimbursement In a non-fee for service environment, upcoming venous trials, appropriate use criteria to limit inappropriate venous care, and more.
The didactic Program L (Sessions 87-94) on Deep Venous Disease will be all day Friday and the sessions will include discussions on illiocaval stenting, wound care, and surgical and interventional management strategies for thromboembolic events in the venous system. A special medical management session will address topics including statin use, reversal agents for the DOAC, and the potential utility of e-selectin inhibition, and more.
In addition, two special non-CME workshops – “Ask the Experts” sessions – are being offered on Wednesday afternoon this year:
Module 1: Current Superficial Venous Treatment, Wounds, and Edema will focus on endothermal therapy, cyanoacrylate, MOCA, VTE and recanalization, perforators, sclerotherapy, CVI and lymphadema, lipedema, and wound care and compression.
Module 2: Thrombus Management will address thrombolysis and thrombectomy, stents, IVUS, valves, and Nutcracker syndrome.
The workshops will include video case presentations, lectures and demonstrations on vein management by experts, plus hands-on opportunities where participants can rotate through multiple training stations staffed by professionals to assist them.
The Venous Venous Venous @VEITHsymposium program has become a popular staple of the the VEITHsymposium. Now in its 13th year, the Venous Venous Venous program, which will be held on Wednesday, Thursday, and Friday, features a mixture of didactic sessions and workshops to cover the full gamut of venous disorders and their treatments, surgical, endovascular, and medical. It is “considered to be the best and most complete program,” on venous diseases according to conference organizers.
The didactic Program I (Sessions 63-70) on Superficial Venous Disease will be held all day Thursday and will detail the latest developments in venous clinical examinations and imaging, superficial vein strategies and techniques, thermal and non-thermal ablation, and there will be a special session on venous societal issues and governance.
Moderated by Kathleen J. Ozsvath, MD, and Harold J. Welch, MD, this special program will feature discussions on the future of venous reimbursement In a non-fee for service environment, upcoming venous trials, appropriate use criteria to limit inappropriate venous care, and more.
The didactic Program L (Sessions 87-94) on Deep Venous Disease will be all day Friday and the sessions will include discussions on illiocaval stenting, wound care, and surgical and interventional management strategies for thromboembolic events in the venous system. A special medical management session will address topics including statin use, reversal agents for the DOAC, and the potential utility of e-selectin inhibition, and more.
In addition, two special non-CME workshops – “Ask the Experts” sessions – are being offered on Wednesday afternoon this year:
Module 1: Current Superficial Venous Treatment, Wounds, and Edema will focus on endothermal therapy, cyanoacrylate, MOCA, VTE and recanalization, perforators, sclerotherapy, CVI and lymphadema, lipedema, and wound care and compression.
Module 2: Thrombus Management will address thrombolysis and thrombectomy, stents, IVUS, valves, and Nutcracker syndrome.
The workshops will include video case presentations, lectures and demonstrations on vein management by experts, plus hands-on opportunities where participants can rotate through multiple training stations staffed by professionals to assist them.
The Venous Venous Venous @VEITHsymposium program has become a popular staple of the the VEITHsymposium. Now in its 13th year, the Venous Venous Venous program, which will be held on Wednesday, Thursday, and Friday, features a mixture of didactic sessions and workshops to cover the full gamut of venous disorders and their treatments, surgical, endovascular, and medical. It is “considered to be the best and most complete program,” on venous diseases according to conference organizers.
The didactic Program I (Sessions 63-70) on Superficial Venous Disease will be held all day Thursday and will detail the latest developments in venous clinical examinations and imaging, superficial vein strategies and techniques, thermal and non-thermal ablation, and there will be a special session on venous societal issues and governance.
Moderated by Kathleen J. Ozsvath, MD, and Harold J. Welch, MD, this special program will feature discussions on the future of venous reimbursement In a non-fee for service environment, upcoming venous trials, appropriate use criteria to limit inappropriate venous care, and more.
The didactic Program L (Sessions 87-94) on Deep Venous Disease will be all day Friday and the sessions will include discussions on illiocaval stenting, wound care, and surgical and interventional management strategies for thromboembolic events in the venous system. A special medical management session will address topics including statin use, reversal agents for the DOAC, and the potential utility of e-selectin inhibition, and more.
In addition, two special non-CME workshops – “Ask the Experts” sessions – are being offered on Wednesday afternoon this year:
Module 1: Current Superficial Venous Treatment, Wounds, and Edema will focus on endothermal therapy, cyanoacrylate, MOCA, VTE and recanalization, perforators, sclerotherapy, CVI and lymphadema, lipedema, and wound care and compression.
Module 2: Thrombus Management will address thrombolysis and thrombectomy, stents, IVUS, valves, and Nutcracker syndrome.
The workshops will include video case presentations, lectures and demonstrations on vein management by experts, plus hands-on opportunities where participants can rotate through multiple training stations staffed by professionals to assist them.
Caring for the carotids a focus of VEITHsymposium
Developments in carotid artery disease diagnosis and treatment have always been an important component of the VEITHsymposium programs and there will be sessions focusing on this critical area of patient management throughout the entire meeting.
The session will be moderated by Bruce A. Perler, MD, and L. Nelson Hopkins, MD, and include presentations on the value of using biomarkers of brain injury associated with carotid interventions, and how to assess and treat such adverse events as cerebral hyperfusion syndrome and intracranial artery dissection, as well as best medical treatments for carotid patients.
Of particular interest, there will be a debate Tuesday on the need for completion imaging with duplex or angiography with Hans-Henning Eckstein, MD, PhD, and R. Clement Darling III, MD.
Presentations will also address some of the latest treatment techniques for carotid artery disease. For example, on Wednesday morning, Norman H. Kumins, MD, of the Cleveland Medical Center, will present a study on the duration of blood flow reversal during transcarotid artery revascularization (TCAR), an “increasingly popular alternative to carotid endarterctomy and transfemoral artery carotid stenting,” which is designed to provide increased neuroprotection during the placement and angioplasty of the carotid stent. They analyzed the relationship between the length of TCAR flow reversal time (FRT) and major adverse events in 307 patients who underwent TCAR at four high-volume institutions. They separated patients into short (3-7minutes); medium(8-12 minutes); and long group (greater than 12 minutes) FRT. They designated a subset of the long group patients of those with greater than or equal to 20 or more minutes FRT, which they defined as the very long group. The stroke, myocardial infarction, and death rates at 30 days were assessed for all patients and were compared them between groups.
Dr. Kumins will detail how the overall stroke rate was 1.3%, with all strokes considered minor, and all patients showing full recovery. The four strokes occurred in patients with FRT of 6, 7, 11, and 12 minutes, showing no difference in the composite stroke/death or stroke/death/MI rates among the groups, the researchers indicated.
Dr. Kumins will discuss how flow reversal time does not affect stroke rates in patients undergoing TCAR, and suggest that operators should focus on the technical aspects of the procedure during flow reversal rather than being concerned about the amount of FRT.
Developments in carotid artery disease diagnosis and treatment have always been an important component of the VEITHsymposium programs and there will be sessions focusing on this critical area of patient management throughout the entire meeting.
The session will be moderated by Bruce A. Perler, MD, and L. Nelson Hopkins, MD, and include presentations on the value of using biomarkers of brain injury associated with carotid interventions, and how to assess and treat such adverse events as cerebral hyperfusion syndrome and intracranial artery dissection, as well as best medical treatments for carotid patients.
Of particular interest, there will be a debate Tuesday on the need for completion imaging with duplex or angiography with Hans-Henning Eckstein, MD, PhD, and R. Clement Darling III, MD.
Presentations will also address some of the latest treatment techniques for carotid artery disease. For example, on Wednesday morning, Norman H. Kumins, MD, of the Cleveland Medical Center, will present a study on the duration of blood flow reversal during transcarotid artery revascularization (TCAR), an “increasingly popular alternative to carotid endarterctomy and transfemoral artery carotid stenting,” which is designed to provide increased neuroprotection during the placement and angioplasty of the carotid stent. They analyzed the relationship between the length of TCAR flow reversal time (FRT) and major adverse events in 307 patients who underwent TCAR at four high-volume institutions. They separated patients into short (3-7minutes); medium(8-12 minutes); and long group (greater than 12 minutes) FRT. They designated a subset of the long group patients of those with greater than or equal to 20 or more minutes FRT, which they defined as the very long group. The stroke, myocardial infarction, and death rates at 30 days were assessed for all patients and were compared them between groups.
Dr. Kumins will detail how the overall stroke rate was 1.3%, with all strokes considered minor, and all patients showing full recovery. The four strokes occurred in patients with FRT of 6, 7, 11, and 12 minutes, showing no difference in the composite stroke/death or stroke/death/MI rates among the groups, the researchers indicated.
Dr. Kumins will discuss how flow reversal time does not affect stroke rates in patients undergoing TCAR, and suggest that operators should focus on the technical aspects of the procedure during flow reversal rather than being concerned about the amount of FRT.
Developments in carotid artery disease diagnosis and treatment have always been an important component of the VEITHsymposium programs and there will be sessions focusing on this critical area of patient management throughout the entire meeting.
The session will be moderated by Bruce A. Perler, MD, and L. Nelson Hopkins, MD, and include presentations on the value of using biomarkers of brain injury associated with carotid interventions, and how to assess and treat such adverse events as cerebral hyperfusion syndrome and intracranial artery dissection, as well as best medical treatments for carotid patients.
Of particular interest, there will be a debate Tuesday on the need for completion imaging with duplex or angiography with Hans-Henning Eckstein, MD, PhD, and R. Clement Darling III, MD.
Presentations will also address some of the latest treatment techniques for carotid artery disease. For example, on Wednesday morning, Norman H. Kumins, MD, of the Cleveland Medical Center, will present a study on the duration of blood flow reversal during transcarotid artery revascularization (TCAR), an “increasingly popular alternative to carotid endarterctomy and transfemoral artery carotid stenting,” which is designed to provide increased neuroprotection during the placement and angioplasty of the carotid stent. They analyzed the relationship between the length of TCAR flow reversal time (FRT) and major adverse events in 307 patients who underwent TCAR at four high-volume institutions. They separated patients into short (3-7minutes); medium(8-12 minutes); and long group (greater than 12 minutes) FRT. They designated a subset of the long group patients of those with greater than or equal to 20 or more minutes FRT, which they defined as the very long group. The stroke, myocardial infarction, and death rates at 30 days were assessed for all patients and were compared them between groups.
Dr. Kumins will detail how the overall stroke rate was 1.3%, with all strokes considered minor, and all patients showing full recovery. The four strokes occurred in patients with FRT of 6, 7, 11, and 12 minutes, showing no difference in the composite stroke/death or stroke/death/MI rates among the groups, the researchers indicated.
Dr. Kumins will discuss how flow reversal time does not affect stroke rates in patients undergoing TCAR, and suggest that operators should focus on the technical aspects of the procedure during flow reversal rather than being concerned about the amount of FRT.
Assessing and treating lower extremity arterial disease
This year at the VEITHsymposium, lower extremity arterial disease diagnosis and treatment takes pride of place in multiple sessions on each day.
For example, Tuesday will feature a special afternoon program on Hot New Topics In Lower Extremity Occlusive Disease Treatment, and on Wednesday morning, an associate faculty session will be held on Progress In Lower Extremity Occlusive Disease And Its Treatments.
In one particular presentation on Wednesday morning, Arsalan Wafi, MBBS, a clinical researcher at St. George’s Vascular Institute, London, will present a 10-year prospective study demonstrating that the poor mobility, lack of statin use, and socioeconomic deprivation are all associated with worse survival after a major lower limb amputation. Dr. Wafi will discuss how he and his colleagues assessed consecutive 805 major lower limb amputation patients seen in the Roehampton Rehabilitation Center between January 2007 and January 2018, using prospective records, which included demographics, etiologies of limb loss, operative details, medications, and mortality data over a 10-year follow-up period.
A total of 611 (76%) occurred in men, and 194 (24%) in women. Etiologies included diabetes mellitus, peripheral vascular disease, and other causes such as trauma, malignancy, sepsis, and complex regional pain syndrome.
Dr. Wafi will present data showing that living in a deprived area and being further away from the rehabilitation center were both significantly associated with poorer survival. Diabetes mellitus or peripheral vascular disease were associated with significantly shorter survival, compared with other etiologies, and not being on a statin was associated with significantly worse survival among the vascular patients. In addition, poorer overall mobility at discharge from rehabilitation was associated with poorer survival, according to the researchers. However there was no significant difference in survival between below-knee and above-knee amputees, or between unilateral and bilateral amputees.
Thursday will be highlighted by a session on New Devices For Treating Lower Extremity Lesions By Endovascular Or Open Techniques, and Friday will see a session New Developments In The Treatment Of Popliteal Diseases And Aneurysms.
This is only one of many such studies focused on lower extremity arterial disease at this year’s VEITHsymposium.
This year at the VEITHsymposium, lower extremity arterial disease diagnosis and treatment takes pride of place in multiple sessions on each day.
For example, Tuesday will feature a special afternoon program on Hot New Topics In Lower Extremity Occlusive Disease Treatment, and on Wednesday morning, an associate faculty session will be held on Progress In Lower Extremity Occlusive Disease And Its Treatments.
In one particular presentation on Wednesday morning, Arsalan Wafi, MBBS, a clinical researcher at St. George’s Vascular Institute, London, will present a 10-year prospective study demonstrating that the poor mobility, lack of statin use, and socioeconomic deprivation are all associated with worse survival after a major lower limb amputation. Dr. Wafi will discuss how he and his colleagues assessed consecutive 805 major lower limb amputation patients seen in the Roehampton Rehabilitation Center between January 2007 and January 2018, using prospective records, which included demographics, etiologies of limb loss, operative details, medications, and mortality data over a 10-year follow-up period.
A total of 611 (76%) occurred in men, and 194 (24%) in women. Etiologies included diabetes mellitus, peripheral vascular disease, and other causes such as trauma, malignancy, sepsis, and complex regional pain syndrome.
Dr. Wafi will present data showing that living in a deprived area and being further away from the rehabilitation center were both significantly associated with poorer survival. Diabetes mellitus or peripheral vascular disease were associated with significantly shorter survival, compared with other etiologies, and not being on a statin was associated with significantly worse survival among the vascular patients. In addition, poorer overall mobility at discharge from rehabilitation was associated with poorer survival, according to the researchers. However there was no significant difference in survival between below-knee and above-knee amputees, or between unilateral and bilateral amputees.
Thursday will be highlighted by a session on New Devices For Treating Lower Extremity Lesions By Endovascular Or Open Techniques, and Friday will see a session New Developments In The Treatment Of Popliteal Diseases And Aneurysms.
This is only one of many such studies focused on lower extremity arterial disease at this year’s VEITHsymposium.
This year at the VEITHsymposium, lower extremity arterial disease diagnosis and treatment takes pride of place in multiple sessions on each day.
For example, Tuesday will feature a special afternoon program on Hot New Topics In Lower Extremity Occlusive Disease Treatment, and on Wednesday morning, an associate faculty session will be held on Progress In Lower Extremity Occlusive Disease And Its Treatments.
In one particular presentation on Wednesday morning, Arsalan Wafi, MBBS, a clinical researcher at St. George’s Vascular Institute, London, will present a 10-year prospective study demonstrating that the poor mobility, lack of statin use, and socioeconomic deprivation are all associated with worse survival after a major lower limb amputation. Dr. Wafi will discuss how he and his colleagues assessed consecutive 805 major lower limb amputation patients seen in the Roehampton Rehabilitation Center between January 2007 and January 2018, using prospective records, which included demographics, etiologies of limb loss, operative details, medications, and mortality data over a 10-year follow-up period.
A total of 611 (76%) occurred in men, and 194 (24%) in women. Etiologies included diabetes mellitus, peripheral vascular disease, and other causes such as trauma, malignancy, sepsis, and complex regional pain syndrome.
Dr. Wafi will present data showing that living in a deprived area and being further away from the rehabilitation center were both significantly associated with poorer survival. Diabetes mellitus or peripheral vascular disease were associated with significantly shorter survival, compared with other etiologies, and not being on a statin was associated with significantly worse survival among the vascular patients. In addition, poorer overall mobility at discharge from rehabilitation was associated with poorer survival, according to the researchers. However there was no significant difference in survival between below-knee and above-knee amputees, or between unilateral and bilateral amputees.
Thursday will be highlighted by a session on New Devices For Treating Lower Extremity Lesions By Endovascular Or Open Techniques, and Friday will see a session New Developments In The Treatment Of Popliteal Diseases And Aneurysms.
This is only one of many such studies focused on lower extremity arterial disease at this year’s VEITHsymposium.
Vaping-linked lung injury: 2,172 cases, 42 deaths
The Centers for Disease Control and Prevention has from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.
Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.
Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
The Centers for Disease Control and Prevention has from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.
Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.
Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
The Centers for Disease Control and Prevention has from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.
Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.
Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
REPORTING FROM CDC
57 Varieties: Sleep-Disordered Breathing Linked to Changes in 1 Important Gene
Blood oxygen levels drop during sleep, but how much and when that happens is mainly hereditary? Now researchers from Brigham and Women’s Hospital and Case Western Reserve University are getting closer to finding the genetic reasons for the fluctuations, which could help people with sleep apnea and other lung illnesses.
In their study, funded by the National Heart, Lung, and Blood Institute (NHLBI), the researchers analyzed whole genome sequence data from the NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. They also incorporated results for family-based linkage analysis, which maps genes with hereditary traits to their location in the genome.
The researchers identified 57 genetic variations of DLC1, a gene consistently associated with average arterial oxyhemoglobin saturation during sleep. The variants explain almost 1% of the variability in the oxygen levels in European Americans. That is high for complex genetic phenotypes, the researchers say. Of the 57 variants, 51 influence and regulate human lung fibroblast cells.
“This study highlights the advantage of using family data in searching for rare variants,” says James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.”
Blood oxygen levels drop during sleep, but how much and when that happens is mainly hereditary? Now researchers from Brigham and Women’s Hospital and Case Western Reserve University are getting closer to finding the genetic reasons for the fluctuations, which could help people with sleep apnea and other lung illnesses.
In their study, funded by the National Heart, Lung, and Blood Institute (NHLBI), the researchers analyzed whole genome sequence data from the NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. They also incorporated results for family-based linkage analysis, which maps genes with hereditary traits to their location in the genome.
The researchers identified 57 genetic variations of DLC1, a gene consistently associated with average arterial oxyhemoglobin saturation during sleep. The variants explain almost 1% of the variability in the oxygen levels in European Americans. That is high for complex genetic phenotypes, the researchers say. Of the 57 variants, 51 influence and regulate human lung fibroblast cells.
“This study highlights the advantage of using family data in searching for rare variants,” says James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.”
Blood oxygen levels drop during sleep, but how much and when that happens is mainly hereditary? Now researchers from Brigham and Women’s Hospital and Case Western Reserve University are getting closer to finding the genetic reasons for the fluctuations, which could help people with sleep apnea and other lung illnesses.
In their study, funded by the National Heart, Lung, and Blood Institute (NHLBI), the researchers analyzed whole genome sequence data from the NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. They also incorporated results for family-based linkage analysis, which maps genes with hereditary traits to their location in the genome.
The researchers identified 57 genetic variations of DLC1, a gene consistently associated with average arterial oxyhemoglobin saturation during sleep. The variants explain almost 1% of the variability in the oxygen levels in European Americans. That is high for complex genetic phenotypes, the researchers say. Of the 57 variants, 51 influence and regulate human lung fibroblast cells.
“This study highlights the advantage of using family data in searching for rare variants,” says James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.”