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VAM Photos Now Available
If you attended the 2019 Vascular Annual Meeting in National Harbor, Md., be sure to check out the many photos now available on the SVS Flickr account. Relive the education sessions, the exhibit hall, the alumni receptions and the marvelous “Vascular Spectacular” gala. View, download and share these as much as you’d like. If you had your headshot taken at the SVS Booth, you can find that photo here.
If you attended the 2019 Vascular Annual Meeting in National Harbor, Md., be sure to check out the many photos now available on the SVS Flickr account. Relive the education sessions, the exhibit hall, the alumni receptions and the marvelous “Vascular Spectacular” gala. View, download and share these as much as you’d like. If you had your headshot taken at the SVS Booth, you can find that photo here.
If you attended the 2019 Vascular Annual Meeting in National Harbor, Md., be sure to check out the many photos now available on the SVS Flickr account. Relive the education sessions, the exhibit hall, the alumni receptions and the marvelous “Vascular Spectacular” gala. View, download and share these as much as you’d like. If you had your headshot taken at the SVS Booth, you can find that photo here.
Bakuchiol
Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.1-6 Specifically, the seeds of as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.7-9
This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.4 The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.3
Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.10 Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.11 Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.12 This column briefly identifies some of the various uses emerging for this compelling botanical agent.
Antiaging activities
In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.13
The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.1
Retinoids without reactions?
In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.14
Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.12 Notably, there is one report to date of an allergic reaction to topical bakuchiol.15
Topical combination therapies for hyperpigmentation, photodamage, and acne
Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.16
A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.17
A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.18
Anticancer activity
In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.2
Skin-whitening potential
In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.19 Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.20
Conclusion
A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.
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. Write to her at [email protected].
References
1. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.
2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.
3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.
4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.
5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.
6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.
7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.
8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.
9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.
10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.
11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.
12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.
13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.
14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.
15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.
16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.
17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.
18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.
19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.
20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.
Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.1-6 Specifically, the seeds of as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.7-9
This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.4 The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.3
Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.10 Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.11 Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.12 This column briefly identifies some of the various uses emerging for this compelling botanical agent.
Antiaging activities
In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.13
The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.1
Retinoids without reactions?
In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.14
Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.12 Notably, there is one report to date of an allergic reaction to topical bakuchiol.15
Topical combination therapies for hyperpigmentation, photodamage, and acne
Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.16
A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.17
A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.18
Anticancer activity
In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.2
Skin-whitening potential
In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.19 Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.20
Conclusion
A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.
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. Write to her at [email protected].
References
1. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.
2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.
3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.
4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.
5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.
6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.
7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.
8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.
9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.
10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.
11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.
12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.
13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.
14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.
15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.
16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.
17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.
18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.
19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.
20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.
Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.1-6 Specifically, the seeds of as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.7-9
This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.4 The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.3
Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.10 Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.11 Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.12 This column briefly identifies some of the various uses emerging for this compelling botanical agent.
Antiaging activities
In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.13
The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.1
Retinoids without reactions?
In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.14
Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.12 Notably, there is one report to date of an allergic reaction to topical bakuchiol.15
Topical combination therapies for hyperpigmentation, photodamage, and acne
Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.16
A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.17
A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.18
Anticancer activity
In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.2
Skin-whitening potential
In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.19 Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.20
Conclusion
A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.
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. Write to her at [email protected].
References
1. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.
2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.
3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.
4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.
5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.
6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.
7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.
8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.
9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.
10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.
11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.
12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.
13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.
14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.
15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.
16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.
17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.
18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.
19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.
20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.
Microvascular disease: An independent and exacerbating risk factor for amputation
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Individuals with microvascular disease (MVD) showed a significantly increased risk of lower limb amputation in the absence of peripheral artery disease (PAD), according to the results of a large database analysis published online in Circulation.
Furthermore, those who had both MVD and PAD had a greater than 20-fold increased risk of amputation than if they had either PAD or MVD alone, according to Joshua A. Beckman, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.
“The novelty of these findings becomes clear when put into the current framework of critical limb ischemia,” they wrote.
“In a recent state of the art review of [critical limb ischemia], MVD as a whole or its components did not receive a single mention. Our work shows that MVD helps identify a population not previously considered at particularly high risk for amputation and, when added to PAD, identify a group of patients at very high risk for amputation,” they continued.
Dr. Beckman and colleagues assessed individuals in the Veterans Aging Cohort Study (VACS), a prospective longitudinal cohort of veterans. They included all VACS participants who were alive as of April 1, 2003 with the baseline as a participant’s first clinic visit on or after this date. Participants were followed from baseline to the minimum of: date of lower extremity amputation, death, or Dec. 31, 2014.
They assessed four levels of vascular involvement: neither MVD nor PAD, MVD alone, PAD alone, and MVD plus PAD, with the primary outcome being lower limb amputation, all based on a variety of measures including appropriate ICD-9 or CPT codes.
The rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years. At the time of amputation, retinopathy was present in 69%, nephropathy in 67%, and neuropathy in 78% of participants.
After multivariable adjustment for 216 demographic characteristics, cardiovascular disease risk factors, and other potential confounders, they found that, compared with participants without either vascular disease, the presence of MVD alone was associated with a 3.7-fold increased risk of amputation, PAD alone conferred a 13.9-fold elevated risk of amputation, and the combination of PAD and MVD was associated with a 22.7-fold increased risk of amputation.
They also found that the location of amputation also varied depending on the type of vascular disease at the time of amputation.
Participants with MVD alone accounted for 18% of all amputations, 21% of below ankle amputations, 15% of below knee amputations, and 6% of all above knee amputations. Participants with PAD alone accounted for 22% of all amputations, 17% of below ankle, 25% of below knee, and 39% of above knee amputations. The combination of MVD and PAD accounted for 45% of all amputation and caused the most amputation at all limb levels. In addition, they found a statistically significant variation in vascular involvement and level of amputation, with MVD more likely to cause a below-ankle amputation and PAD more likely to cause below- and above-knee amputations (P less than .001)
“MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation,” the researchers concluded.
The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
SOURCE: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
FROM CIRCULATION
Key clinical point: Microvascular disease yielded a 3.7-fold increased risk of lower limb amputation.
Major finding:
Study details: Database analysis of 125,674 participants in the Veterans Aging Cohort Study from April 2003 through December 2014.
Disclosures: The study was supported by grants from the American Heart Association. Dr. Beckman reported consulting for multiple pharmaceutical companies and serving on the DSMC for Bayer and Novartis.
Source: Beckman JA et al. Circulation. 2019. doi: 10.1161/CIRCULATIONAHA.119.040672.
Y 2 the ED? (Why patients go to the emergency department)
Along with terminal care and inflated drug prices, the excessive number of “inappropriate” ED visits often is cited as a major driver of health care costs in the United States. Why do so many patients choose to go to the ED for complaints that might be better or more economically treated in another setting?
A report by two researchers in the division of emergency medicine at the Boston Children’s Hospital that appeared in the June 2019 Pediatrics suggests that, at least for pediatric patients, “increased insurance coverage neither drove nor counteracted” the recent trends in ED visits. (“Trends in Pediatric Emergency Department Use After the Affordable Care Act,” Pediatrics. 2019 Jun 1. doi: 10.1542/peds.2018-3542).
I guess it’s not surprising – and somewhat comforting – to learn that, when parents believe their child has an emergent condition they give little thought to the cost of care. Is the trend of increasing ED use a result of an evolving definition of an “emergency”? Your grandparents, or certainly your great grandparents, might claim that, when they were young most minor injuries were handled at home, or at least in the neighborhood by someone with first aid experience who wasn’t put off by the sight of blood. However, a trend away from self-reliance in everything from food preparation to auto repair, combined with media overexposure to the serious complications of apparently minor illness and injury, has left most parents feeling fearful and helpless in the face of adversity.
We have to accept as a given that many parents are going to interpret their child’s situation as emergent, even though you and I might not. But what are the factors that prompt a concerned parent to take his child to the ED instead of a physician’s office? It may simply be the path of least resistance. The parent’s past experience may include frustrating and time-consuming attempts to navigate a clunky phone system only to be met by a receptionist or triage nurse who seems more committed to deflecting calls and protecting the physician’s schedule than getting the patient seen.
The call may miraculously get through to someone with a caring voice and the patience to listen, but the parent then learns that the office doesn’t do minor wound care or he is told that the physician almost certainly will want to do an x-ray of any injured extremity and that the ED is a better choice. It doesn’t take very many scenarios like this to prompt a parent to make his first and only call to the ED. To some extent, physician behavior has helped mold parents’ definition of an emergency.
We are encouraged to make our offices a “medical home.” However, it appears the medical home model is one that is built around chronic conditions and behavioral problems and gives little attention to the acute complaints. When you came running into the house with a skinned knee, did your mother tell to you go across the street to the neighbor’s house because blood made her squeamish and she didn’t have any bandages?
There are ways to structure an office and a schedule which are more welcoming to patients with minor emergencies, and I know it is a difficult sell to physicians who are handcuffed by their EHRs and already overwhelmed by patients with time-consuming behavioral complaints. However, if your practice is facing competition from pop-up urgent care centers or if you are increasingly troubled that your patients are receiving fragmented care, it may not be too late to make your practice into a true medical home that welcomes minor emergencies.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Along with terminal care and inflated drug prices, the excessive number of “inappropriate” ED visits often is cited as a major driver of health care costs in the United States. Why do so many patients choose to go to the ED for complaints that might be better or more economically treated in another setting?
A report by two researchers in the division of emergency medicine at the Boston Children’s Hospital that appeared in the June 2019 Pediatrics suggests that, at least for pediatric patients, “increased insurance coverage neither drove nor counteracted” the recent trends in ED visits. (“Trends in Pediatric Emergency Department Use After the Affordable Care Act,” Pediatrics. 2019 Jun 1. doi: 10.1542/peds.2018-3542).
I guess it’s not surprising – and somewhat comforting – to learn that, when parents believe their child has an emergent condition they give little thought to the cost of care. Is the trend of increasing ED use a result of an evolving definition of an “emergency”? Your grandparents, or certainly your great grandparents, might claim that, when they were young most minor injuries were handled at home, or at least in the neighborhood by someone with first aid experience who wasn’t put off by the sight of blood. However, a trend away from self-reliance in everything from food preparation to auto repair, combined with media overexposure to the serious complications of apparently minor illness and injury, has left most parents feeling fearful and helpless in the face of adversity.
We have to accept as a given that many parents are going to interpret their child’s situation as emergent, even though you and I might not. But what are the factors that prompt a concerned parent to take his child to the ED instead of a physician’s office? It may simply be the path of least resistance. The parent’s past experience may include frustrating and time-consuming attempts to navigate a clunky phone system only to be met by a receptionist or triage nurse who seems more committed to deflecting calls and protecting the physician’s schedule than getting the patient seen.
The call may miraculously get through to someone with a caring voice and the patience to listen, but the parent then learns that the office doesn’t do minor wound care or he is told that the physician almost certainly will want to do an x-ray of any injured extremity and that the ED is a better choice. It doesn’t take very many scenarios like this to prompt a parent to make his first and only call to the ED. To some extent, physician behavior has helped mold parents’ definition of an emergency.
We are encouraged to make our offices a “medical home.” However, it appears the medical home model is one that is built around chronic conditions and behavioral problems and gives little attention to the acute complaints. When you came running into the house with a skinned knee, did your mother tell to you go across the street to the neighbor’s house because blood made her squeamish and she didn’t have any bandages?
There are ways to structure an office and a schedule which are more welcoming to patients with minor emergencies, and I know it is a difficult sell to physicians who are handcuffed by their EHRs and already overwhelmed by patients with time-consuming behavioral complaints. However, if your practice is facing competition from pop-up urgent care centers or if you are increasingly troubled that your patients are receiving fragmented care, it may not be too late to make your practice into a true medical home that welcomes minor emergencies.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Along with terminal care and inflated drug prices, the excessive number of “inappropriate” ED visits often is cited as a major driver of health care costs in the United States. Why do so many patients choose to go to the ED for complaints that might be better or more economically treated in another setting?
A report by two researchers in the division of emergency medicine at the Boston Children’s Hospital that appeared in the June 2019 Pediatrics suggests that, at least for pediatric patients, “increased insurance coverage neither drove nor counteracted” the recent trends in ED visits. (“Trends in Pediatric Emergency Department Use After the Affordable Care Act,” Pediatrics. 2019 Jun 1. doi: 10.1542/peds.2018-3542).
I guess it’s not surprising – and somewhat comforting – to learn that, when parents believe their child has an emergent condition they give little thought to the cost of care. Is the trend of increasing ED use a result of an evolving definition of an “emergency”? Your grandparents, or certainly your great grandparents, might claim that, when they were young most minor injuries were handled at home, or at least in the neighborhood by someone with first aid experience who wasn’t put off by the sight of blood. However, a trend away from self-reliance in everything from food preparation to auto repair, combined with media overexposure to the serious complications of apparently minor illness and injury, has left most parents feeling fearful and helpless in the face of adversity.
We have to accept as a given that many parents are going to interpret their child’s situation as emergent, even though you and I might not. But what are the factors that prompt a concerned parent to take his child to the ED instead of a physician’s office? It may simply be the path of least resistance. The parent’s past experience may include frustrating and time-consuming attempts to navigate a clunky phone system only to be met by a receptionist or triage nurse who seems more committed to deflecting calls and protecting the physician’s schedule than getting the patient seen.
The call may miraculously get through to someone with a caring voice and the patience to listen, but the parent then learns that the office doesn’t do minor wound care or he is told that the physician almost certainly will want to do an x-ray of any injured extremity and that the ED is a better choice. It doesn’t take very many scenarios like this to prompt a parent to make his first and only call to the ED. To some extent, physician behavior has helped mold parents’ definition of an emergency.
We are encouraged to make our offices a “medical home.” However, it appears the medical home model is one that is built around chronic conditions and behavioral problems and gives little attention to the acute complaints. When you came running into the house with a skinned knee, did your mother tell to you go across the street to the neighbor’s house because blood made her squeamish and she didn’t have any bandages?
There are ways to structure an office and a schedule which are more welcoming to patients with minor emergencies, and I know it is a difficult sell to physicians who are handcuffed by their EHRs and already overwhelmed by patients with time-consuming behavioral complaints. However, if your practice is facing competition from pop-up urgent care centers or if you are increasingly troubled that your patients are receiving fragmented care, it may not be too late to make your practice into a true medical home that welcomes minor emergencies.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Acquired MMR immunity doesn’t last to age 1 year
according to results of a study in Vaccine.
María José Cilleruelo, PhD, of Hospital Universitario Puerta de Hierro in Majadahonda, Spain, and colleagues showed that, although most infants acquire some protective antibodies against MMR from their mothers during gestation, most have lost this protection as early as 3 months of age. This single-center, observational, prospective study was conducted between October 2013 and December 2014, and it began with 146 mother-child pairs, with 99 remaining in follow-up at 3 months, 77 at 6 months, 63 at 9 months, and 30 at 12 months. For measles, 88% of newborns were seropositive, but only 19% were at 3 months; for mumps, 70% of newborns were seropositive, but only 11% were at 3 months; and for rubella, 91% of newborns were seropositive, but only 13% were at 3 months. No infants were seropositive for mumps or rubella at 9 months, and only 2% were for measles. No infants were seropositive for any of these viruses by 12 months of age.
The investigators noted that, given Spain (where the study was conducted) is a country that gives the first MMR vaccine at 12 months of life, these declining titers can leave most infants vulnerable to those viruses before then.
“We suggest that it may be worth considering administering the first dose of MMR vaccine before 12 months of age,” the investigators concluded, although they advised studies be undertaken into the efficacy and safety of administration of that vaccine in infants younger than 12 months. They noted that the biggest limitation of this study was the high percentage of loss to follow-up, which limited the statistical power to make comparisons.
The study was funded by the Fondo de Investigación Sanitaria, and one of the authors was funded by CIBER de Epidemiología y Salud Pública. The authors declared that there are no conflicts of interest.
SOURCE: Cilleruelo MJ et al. Vaccine. 2019;37:4164-71.
according to results of a study in Vaccine.
María José Cilleruelo, PhD, of Hospital Universitario Puerta de Hierro in Majadahonda, Spain, and colleagues showed that, although most infants acquire some protective antibodies against MMR from their mothers during gestation, most have lost this protection as early as 3 months of age. This single-center, observational, prospective study was conducted between October 2013 and December 2014, and it began with 146 mother-child pairs, with 99 remaining in follow-up at 3 months, 77 at 6 months, 63 at 9 months, and 30 at 12 months. For measles, 88% of newborns were seropositive, but only 19% were at 3 months; for mumps, 70% of newborns were seropositive, but only 11% were at 3 months; and for rubella, 91% of newborns were seropositive, but only 13% were at 3 months. No infants were seropositive for mumps or rubella at 9 months, and only 2% were for measles. No infants were seropositive for any of these viruses by 12 months of age.
The investigators noted that, given Spain (where the study was conducted) is a country that gives the first MMR vaccine at 12 months of life, these declining titers can leave most infants vulnerable to those viruses before then.
“We suggest that it may be worth considering administering the first dose of MMR vaccine before 12 months of age,” the investigators concluded, although they advised studies be undertaken into the efficacy and safety of administration of that vaccine in infants younger than 12 months. They noted that the biggest limitation of this study was the high percentage of loss to follow-up, which limited the statistical power to make comparisons.
The study was funded by the Fondo de Investigación Sanitaria, and one of the authors was funded by CIBER de Epidemiología y Salud Pública. The authors declared that there are no conflicts of interest.
SOURCE: Cilleruelo MJ et al. Vaccine. 2019;37:4164-71.
according to results of a study in Vaccine.
María José Cilleruelo, PhD, of Hospital Universitario Puerta de Hierro in Majadahonda, Spain, and colleagues showed that, although most infants acquire some protective antibodies against MMR from their mothers during gestation, most have lost this protection as early as 3 months of age. This single-center, observational, prospective study was conducted between October 2013 and December 2014, and it began with 146 mother-child pairs, with 99 remaining in follow-up at 3 months, 77 at 6 months, 63 at 9 months, and 30 at 12 months. For measles, 88% of newborns were seropositive, but only 19% were at 3 months; for mumps, 70% of newborns were seropositive, but only 11% were at 3 months; and for rubella, 91% of newborns were seropositive, but only 13% were at 3 months. No infants were seropositive for mumps or rubella at 9 months, and only 2% were for measles. No infants were seropositive for any of these viruses by 12 months of age.
The investigators noted that, given Spain (where the study was conducted) is a country that gives the first MMR vaccine at 12 months of life, these declining titers can leave most infants vulnerable to those viruses before then.
“We suggest that it may be worth considering administering the first dose of MMR vaccine before 12 months of age,” the investigators concluded, although they advised studies be undertaken into the efficacy and safety of administration of that vaccine in infants younger than 12 months. They noted that the biggest limitation of this study was the high percentage of loss to follow-up, which limited the statistical power to make comparisons.
The study was funded by the Fondo de Investigación Sanitaria, and one of the authors was funded by CIBER de Epidemiología y Salud Pública. The authors declared that there are no conflicts of interest.
SOURCE: Cilleruelo MJ et al. Vaccine. 2019;37:4164-71.
FROM VACCINE
Consider cutaneous endometriosis in women with umbilical lesions
according to Liza Raffi of the University of Southern California, Los Angeles, and associates.
The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.
At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.
Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.
The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.
“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”
Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.
SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.
according to Liza Raffi of the University of Southern California, Los Angeles, and associates.
The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.
At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.
Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.
The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.
“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”
Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.
SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.
according to Liza Raffi of the University of Southern California, Los Angeles, and associates.
The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.
At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.
Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.
The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.
“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”
Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.
SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.
FROM THE INTERNATIONAL JOURNAL OF WOMEN’S DERMATOLOGY
LAIV doesn’t up asthmatic children’s risk of lower respiratory events
, according to an analysis published in Vaccine.
The data corroborate other research indicating that live attenuated influenza vaccine (LAIV) is safe for children with asthma older than 2 years and suggest that the choice of vaccination in this population should be based on effectiveness, according to James D. Nordin, MD, MPH, a clinical researcher at HealthPartners Institute in Minneapolis, and colleagues.
Children and adolescents with asthma have an increased risk of morbidity if they contract influenza. They represent a disproportionate number of pediatric influenza hospitalizations and have been a focus of efforts to vaccinate children against influenza. Since 2003, the inactivated influenza vaccine (IIV) and the LAIV have been available. Research indicates that LAIV is more effective than IIV at preventing culture-confirmed influenza in children. Two studies found an increased risk of wheezing in children who received LAIV, but other studies failed to replicate these findings.
A retrospective cohort study
Dr. Nordin and associates conducted a retrospective observational cohort study to investigate whether use of a guideline recommending LAIV for children aged 2 years and older with asthma increased the risk of lower respiratory events within 21 or 42 days of vaccination, compared with standard guidelines to administer IIV in children with asthma. The investigators drew data from two large medical groups with independent clinical leadership that serve demographically similar populations in Minnesota. One group (the LAIV group) switched its preference for all children from IIV to LAIV in 2010. The control group continued using IIV for children with asthma throughout the study period. Each group operates more than 20 clinics.
The investigators included children and adolescents aged 2-17 years who presented during one or more influenza season from 2007-2008 through 2014-2015. Eligible participants had a diagnosis of asthma or wheezing, received one or more influenza vaccines, had continuous insurance enrollment, and had at least one primary care or asthma related subspecialty encounter. They excluded patients with contraindications for LAIV (e.g., pregnancy, malignancy, and cystic fibrosis) and those with any hospitalization, ED visit, or outpatient encounter for a lower respiratory event in the 42 days before influenza vaccination.
Dr. Nordin and colleagues used a generalized estimating equation regression to estimate the ratio of rate ratios (RORs) comparing events before and after vaccination between the LAIV guideline and control groups. The researchers examined covariates such as age, gender, race or ethnicity, Medicaid insurance for at least 1 month in the previous year, neighborhood poverty, and neighborhood rates of asthma.
No increased risk
The investigators included 4,771 children and 7,851 child-influenza records in their analysis. During the period from 2007 to 2010, there were 2,215 child-influenza records from children and adolescents included from the LAIV group and 735 from the IIV guideline group. From 2010 to 2015, there were 3,767 child-influenza records in children and adolescents from the LAIV group and 1,134 from the IIV guideline group. After the LAIV group adopted the new guideline, the proportion of patients receiving LAIV increased from 23% to 68% in the LAIV group and from 7% to 11% in the control group.
About 88% of lower respiratory events included diagnoses for asthma exacerbations. When the investigators adjusted the data for age, asthma severity, asthma control, race or ethnicity, and Medicaid coverage, they found no increase in lower respiratory events associated with the LAIV guideline. The adjusted ROR was 0.74 for lower respiratory events within 21 days of vaccination and 0.77 for lower respiratory events within 42 days of vaccination. The results were similar when Dr. Nordin and colleagues stratified the data by age group, and including additional covariates did not alter the ROR estimates. In all, 21 hospitalizations occurred within 42 days of influenza vaccination, and the LAIV guideline did not increase the risk for hospitalization.
“Findings from this study are consistent with several recent observational studies of LAIV in children and adolescents with asthma,” said Dr. Nordin and colleagues.
One limitation of the current study was that the data were restricted to the information available in electronic health care or claims records. The researchers therefore were able to observe only medically attended lower respiratory events. Furthermore, the exclusion of asthma management encounters and the classification of asthma severity were based on diagnoses, visits, and medication orders and fills. The estimates thus are prone to misclassification, which may have biased the results. Finally, information on important variables such as daycare attendance, presence of school-age siblings, and exposure to secondhand smoke was not available.
The research was funded by a grant from the National Institute of Allergy and Infectious Diseases. The authors had no relevant financial disclosures.
SOURCE: Nordin JD et al. Vaccine. 2019 Jun 10. doi: 10.1016/j.vaccine.2019.05.081.
, according to an analysis published in Vaccine.
The data corroborate other research indicating that live attenuated influenza vaccine (LAIV) is safe for children with asthma older than 2 years and suggest that the choice of vaccination in this population should be based on effectiveness, according to James D. Nordin, MD, MPH, a clinical researcher at HealthPartners Institute in Minneapolis, and colleagues.
Children and adolescents with asthma have an increased risk of morbidity if they contract influenza. They represent a disproportionate number of pediatric influenza hospitalizations and have been a focus of efforts to vaccinate children against influenza. Since 2003, the inactivated influenza vaccine (IIV) and the LAIV have been available. Research indicates that LAIV is more effective than IIV at preventing culture-confirmed influenza in children. Two studies found an increased risk of wheezing in children who received LAIV, but other studies failed to replicate these findings.
A retrospective cohort study
Dr. Nordin and associates conducted a retrospective observational cohort study to investigate whether use of a guideline recommending LAIV for children aged 2 years and older with asthma increased the risk of lower respiratory events within 21 or 42 days of vaccination, compared with standard guidelines to administer IIV in children with asthma. The investigators drew data from two large medical groups with independent clinical leadership that serve demographically similar populations in Minnesota. One group (the LAIV group) switched its preference for all children from IIV to LAIV in 2010. The control group continued using IIV for children with asthma throughout the study period. Each group operates more than 20 clinics.
The investigators included children and adolescents aged 2-17 years who presented during one or more influenza season from 2007-2008 through 2014-2015. Eligible participants had a diagnosis of asthma or wheezing, received one or more influenza vaccines, had continuous insurance enrollment, and had at least one primary care or asthma related subspecialty encounter. They excluded patients with contraindications for LAIV (e.g., pregnancy, malignancy, and cystic fibrosis) and those with any hospitalization, ED visit, or outpatient encounter for a lower respiratory event in the 42 days before influenza vaccination.
Dr. Nordin and colleagues used a generalized estimating equation regression to estimate the ratio of rate ratios (RORs) comparing events before and after vaccination between the LAIV guideline and control groups. The researchers examined covariates such as age, gender, race or ethnicity, Medicaid insurance for at least 1 month in the previous year, neighborhood poverty, and neighborhood rates of asthma.
No increased risk
The investigators included 4,771 children and 7,851 child-influenza records in their analysis. During the period from 2007 to 2010, there were 2,215 child-influenza records from children and adolescents included from the LAIV group and 735 from the IIV guideline group. From 2010 to 2015, there were 3,767 child-influenza records in children and adolescents from the LAIV group and 1,134 from the IIV guideline group. After the LAIV group adopted the new guideline, the proportion of patients receiving LAIV increased from 23% to 68% in the LAIV group and from 7% to 11% in the control group.
About 88% of lower respiratory events included diagnoses for asthma exacerbations. When the investigators adjusted the data for age, asthma severity, asthma control, race or ethnicity, and Medicaid coverage, they found no increase in lower respiratory events associated with the LAIV guideline. The adjusted ROR was 0.74 for lower respiratory events within 21 days of vaccination and 0.77 for lower respiratory events within 42 days of vaccination. The results were similar when Dr. Nordin and colleagues stratified the data by age group, and including additional covariates did not alter the ROR estimates. In all, 21 hospitalizations occurred within 42 days of influenza vaccination, and the LAIV guideline did not increase the risk for hospitalization.
“Findings from this study are consistent with several recent observational studies of LAIV in children and adolescents with asthma,” said Dr. Nordin and colleagues.
One limitation of the current study was that the data were restricted to the information available in electronic health care or claims records. The researchers therefore were able to observe only medically attended lower respiratory events. Furthermore, the exclusion of asthma management encounters and the classification of asthma severity were based on diagnoses, visits, and medication orders and fills. The estimates thus are prone to misclassification, which may have biased the results. Finally, information on important variables such as daycare attendance, presence of school-age siblings, and exposure to secondhand smoke was not available.
The research was funded by a grant from the National Institute of Allergy and Infectious Diseases. The authors had no relevant financial disclosures.
SOURCE: Nordin JD et al. Vaccine. 2019 Jun 10. doi: 10.1016/j.vaccine.2019.05.081.
, according to an analysis published in Vaccine.
The data corroborate other research indicating that live attenuated influenza vaccine (LAIV) is safe for children with asthma older than 2 years and suggest that the choice of vaccination in this population should be based on effectiveness, according to James D. Nordin, MD, MPH, a clinical researcher at HealthPartners Institute in Minneapolis, and colleagues.
Children and adolescents with asthma have an increased risk of morbidity if they contract influenza. They represent a disproportionate number of pediatric influenza hospitalizations and have been a focus of efforts to vaccinate children against influenza. Since 2003, the inactivated influenza vaccine (IIV) and the LAIV have been available. Research indicates that LAIV is more effective than IIV at preventing culture-confirmed influenza in children. Two studies found an increased risk of wheezing in children who received LAIV, but other studies failed to replicate these findings.
A retrospective cohort study
Dr. Nordin and associates conducted a retrospective observational cohort study to investigate whether use of a guideline recommending LAIV for children aged 2 years and older with asthma increased the risk of lower respiratory events within 21 or 42 days of vaccination, compared with standard guidelines to administer IIV in children with asthma. The investigators drew data from two large medical groups with independent clinical leadership that serve demographically similar populations in Minnesota. One group (the LAIV group) switched its preference for all children from IIV to LAIV in 2010. The control group continued using IIV for children with asthma throughout the study period. Each group operates more than 20 clinics.
The investigators included children and adolescents aged 2-17 years who presented during one or more influenza season from 2007-2008 through 2014-2015. Eligible participants had a diagnosis of asthma or wheezing, received one or more influenza vaccines, had continuous insurance enrollment, and had at least one primary care or asthma related subspecialty encounter. They excluded patients with contraindications for LAIV (e.g., pregnancy, malignancy, and cystic fibrosis) and those with any hospitalization, ED visit, or outpatient encounter for a lower respiratory event in the 42 days before influenza vaccination.
Dr. Nordin and colleagues used a generalized estimating equation regression to estimate the ratio of rate ratios (RORs) comparing events before and after vaccination between the LAIV guideline and control groups. The researchers examined covariates such as age, gender, race or ethnicity, Medicaid insurance for at least 1 month in the previous year, neighborhood poverty, and neighborhood rates of asthma.
No increased risk
The investigators included 4,771 children and 7,851 child-influenza records in their analysis. During the period from 2007 to 2010, there were 2,215 child-influenza records from children and adolescents included from the LAIV group and 735 from the IIV guideline group. From 2010 to 2015, there were 3,767 child-influenza records in children and adolescents from the LAIV group and 1,134 from the IIV guideline group. After the LAIV group adopted the new guideline, the proportion of patients receiving LAIV increased from 23% to 68% in the LAIV group and from 7% to 11% in the control group.
About 88% of lower respiratory events included diagnoses for asthma exacerbations. When the investigators adjusted the data for age, asthma severity, asthma control, race or ethnicity, and Medicaid coverage, they found no increase in lower respiratory events associated with the LAIV guideline. The adjusted ROR was 0.74 for lower respiratory events within 21 days of vaccination and 0.77 for lower respiratory events within 42 days of vaccination. The results were similar when Dr. Nordin and colleagues stratified the data by age group, and including additional covariates did not alter the ROR estimates. In all, 21 hospitalizations occurred within 42 days of influenza vaccination, and the LAIV guideline did not increase the risk for hospitalization.
“Findings from this study are consistent with several recent observational studies of LAIV in children and adolescents with asthma,” said Dr. Nordin and colleagues.
One limitation of the current study was that the data were restricted to the information available in electronic health care or claims records. The researchers therefore were able to observe only medically attended lower respiratory events. Furthermore, the exclusion of asthma management encounters and the classification of asthma severity were based on diagnoses, visits, and medication orders and fills. The estimates thus are prone to misclassification, which may have biased the results. Finally, information on important variables such as daycare attendance, presence of school-age siblings, and exposure to secondhand smoke was not available.
The research was funded by a grant from the National Institute of Allergy and Infectious Diseases. The authors had no relevant financial disclosures.
SOURCE: Nordin JD et al. Vaccine. 2019 Jun 10. doi: 10.1016/j.vaccine.2019.05.081.
FROM VACCINE
Treatment in prison systems might lead to drop in overdose deaths
Incarceration versus treatment takes center stage in a new analysis of U.S. data from researchers in the United Kingdom.
The researchers performed an observational study looking at rates of incarceration, income, and drug-related deaths from 1983 to 2014 in the United States. They found a strong association between incarceration rates and drug-related deaths. Also, a very strong association was found between lower household income and drug-related deaths. Strikingly, in the counties with the highest incarceration rates, there was a 50% higher rate of drug deaths, reported Elias Nosrati, PhD, and associates (Lancet Public Health. 2019 Jul 3;4:e326-33). It is clearer every day that our opioid epidemic was in part wrought by a zealous push to change protocols on treating chronic pain. The epidemic also appears tied to well-meaning but overprescribing doctors and allegedly unscrupulous pharmaceutical companies and distributors. What we are learning through this most recent study is that another factor tied to the opioid and overdose epidemic could be incarceration.
According to the study, an increase in crime rates combined with sentencing reforms led the number of people incarcerated in state and federal prisons to soar from less than 200,000 in 1970 to almost 1 million in 1995. Furthermore, Dr. Nosrati and associates wrote, “Incarceration is directly associated with stigma, discrimination, poor mental health, and chronic economic hardship, all of which are linked to drug use disorders.”
Treatment for drug addiction in prison systems is rare, as is adequate mental health treatment. However, treatment for this population would likely help reduce drug overdose deaths and improve the quality of life for people who are incarcerated and their families. In the Philadelphia prison system, for example, treatment for inmates is available for opioid addiction, both with methadone and now more recently with buprenorphine (Suboxone). The Philadelphia Department of Prisons also provides cognitive-behavioral therapy. In Florida, Chapter 397 of the Florida statutes – known as the Marchman Act – provides for the involuntary (and voluntary) treatment of individuals with substance abuse problems.
The court systems in South Florida have a robust drug-diversion program, aimed at directing people facing incarceration for drug offenses into treatment instead. North Carolina has studied this issue specifically and found through a model simulation that diverting 10% of drug-abusing offenders out of incarceration into treatment would save $4.8 billion in legal costs for North Carolina counties and state legal systems. Diverting 40% of individuals would close to triple that savings.
There are striking data from programs treating individuals who are leveraged into treatment in order to maintain professional licenses. These such individuals, many of whom are physicians, airline pilots, and nurses, have a rate of sobriety of 90% or greater after 5 years. This data show that
In addition to the potential reduction in morbidity and mortality as well as the financial savings, why is treatment important? Because of societal costs. When parents or family members are put in jail for a drug charge or other charge, they leave behind a community, family, and very often children who are affected economically, emotionally, and socially. Those children in particular have higher risks of depression and PTSD. Diverting an offender into treatment or treating an incarcerated person for drug and mental health problems can change the life of a child or family member, and ultimately can change society.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
Incarceration versus treatment takes center stage in a new analysis of U.S. data from researchers in the United Kingdom.
The researchers performed an observational study looking at rates of incarceration, income, and drug-related deaths from 1983 to 2014 in the United States. They found a strong association between incarceration rates and drug-related deaths. Also, a very strong association was found between lower household income and drug-related deaths. Strikingly, in the counties with the highest incarceration rates, there was a 50% higher rate of drug deaths, reported Elias Nosrati, PhD, and associates (Lancet Public Health. 2019 Jul 3;4:e326-33). It is clearer every day that our opioid epidemic was in part wrought by a zealous push to change protocols on treating chronic pain. The epidemic also appears tied to well-meaning but overprescribing doctors and allegedly unscrupulous pharmaceutical companies and distributors. What we are learning through this most recent study is that another factor tied to the opioid and overdose epidemic could be incarceration.
According to the study, an increase in crime rates combined with sentencing reforms led the number of people incarcerated in state and federal prisons to soar from less than 200,000 in 1970 to almost 1 million in 1995. Furthermore, Dr. Nosrati and associates wrote, “Incarceration is directly associated with stigma, discrimination, poor mental health, and chronic economic hardship, all of which are linked to drug use disorders.”
Treatment for drug addiction in prison systems is rare, as is adequate mental health treatment. However, treatment for this population would likely help reduce drug overdose deaths and improve the quality of life for people who are incarcerated and their families. In the Philadelphia prison system, for example, treatment for inmates is available for opioid addiction, both with methadone and now more recently with buprenorphine (Suboxone). The Philadelphia Department of Prisons also provides cognitive-behavioral therapy. In Florida, Chapter 397 of the Florida statutes – known as the Marchman Act – provides for the involuntary (and voluntary) treatment of individuals with substance abuse problems.
The court systems in South Florida have a robust drug-diversion program, aimed at directing people facing incarceration for drug offenses into treatment instead. North Carolina has studied this issue specifically and found through a model simulation that diverting 10% of drug-abusing offenders out of incarceration into treatment would save $4.8 billion in legal costs for North Carolina counties and state legal systems. Diverting 40% of individuals would close to triple that savings.
There are striking data from programs treating individuals who are leveraged into treatment in order to maintain professional licenses. These such individuals, many of whom are physicians, airline pilots, and nurses, have a rate of sobriety of 90% or greater after 5 years. This data show that
In addition to the potential reduction in morbidity and mortality as well as the financial savings, why is treatment important? Because of societal costs. When parents or family members are put in jail for a drug charge or other charge, they leave behind a community, family, and very often children who are affected economically, emotionally, and socially. Those children in particular have higher risks of depression and PTSD. Diverting an offender into treatment or treating an incarcerated person for drug and mental health problems can change the life of a child or family member, and ultimately can change society.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
Incarceration versus treatment takes center stage in a new analysis of U.S. data from researchers in the United Kingdom.
The researchers performed an observational study looking at rates of incarceration, income, and drug-related deaths from 1983 to 2014 in the United States. They found a strong association between incarceration rates and drug-related deaths. Also, a very strong association was found between lower household income and drug-related deaths. Strikingly, in the counties with the highest incarceration rates, there was a 50% higher rate of drug deaths, reported Elias Nosrati, PhD, and associates (Lancet Public Health. 2019 Jul 3;4:e326-33). It is clearer every day that our opioid epidemic was in part wrought by a zealous push to change protocols on treating chronic pain. The epidemic also appears tied to well-meaning but overprescribing doctors and allegedly unscrupulous pharmaceutical companies and distributors. What we are learning through this most recent study is that another factor tied to the opioid and overdose epidemic could be incarceration.
According to the study, an increase in crime rates combined with sentencing reforms led the number of people incarcerated in state and federal prisons to soar from less than 200,000 in 1970 to almost 1 million in 1995. Furthermore, Dr. Nosrati and associates wrote, “Incarceration is directly associated with stigma, discrimination, poor mental health, and chronic economic hardship, all of which are linked to drug use disorders.”
Treatment for drug addiction in prison systems is rare, as is adequate mental health treatment. However, treatment for this population would likely help reduce drug overdose deaths and improve the quality of life for people who are incarcerated and their families. In the Philadelphia prison system, for example, treatment for inmates is available for opioid addiction, both with methadone and now more recently with buprenorphine (Suboxone). The Philadelphia Department of Prisons also provides cognitive-behavioral therapy. In Florida, Chapter 397 of the Florida statutes – known as the Marchman Act – provides for the involuntary (and voluntary) treatment of individuals with substance abuse problems.
The court systems in South Florida have a robust drug-diversion program, aimed at directing people facing incarceration for drug offenses into treatment instead. North Carolina has studied this issue specifically and found through a model simulation that diverting 10% of drug-abusing offenders out of incarceration into treatment would save $4.8 billion in legal costs for North Carolina counties and state legal systems. Diverting 40% of individuals would close to triple that savings.
There are striking data from programs treating individuals who are leveraged into treatment in order to maintain professional licenses. These such individuals, many of whom are physicians, airline pilots, and nurses, have a rate of sobriety of 90% or greater after 5 years. This data show that
In addition to the potential reduction in morbidity and mortality as well as the financial savings, why is treatment important? Because of societal costs. When parents or family members are put in jail for a drug charge or other charge, they leave behind a community, family, and very often children who are affected economically, emotionally, and socially. Those children in particular have higher risks of depression and PTSD. Diverting an offender into treatment or treating an incarcerated person for drug and mental health problems can change the life of a child or family member, and ultimately can change society.
Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
The FDA has revised its guidance on fish consumption
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
The revision touts the health benefits of fish and shellfish and promotes safer fish choices for those who should limit mercury exposure – including women who are or might become pregnant, women who are breastfeeding, and young children.
Those individuals should avoid commercial fish with the highest levels of mercury and should instead choose from “the many types of fish that are lower in mercury – including ones commonly found in grocery stores, such as salmon, shrimp, pollock, canned light tuna, tilapia, catfish, and cod,” according to an FDA press statement.
The potential health benefits of eating fish were highlighted in the U.S. Department of Health and Human Services/Department of Agriculture 2015-2020 Dietary Guidelines for Americans, and in 2017 the FDA and the Environmental Protection Agency released advice on fish consumption, including a user-friendly reference chart regarding mercury levels in various types of fish.
Although the information in the chart has not changed, the FDA revised its advice to expand on the “information about the benefits of fish as part of healthy eating patterns by promoting the science-based recommendations of the 2015-2020 Dietary Guidelines for Americans.”
The advice calls for consumption of at least 8 ounces of seafood per week for adults (less for children) based on a 2,000 calorie diet, and for women who are pregnant or breastfeeding, 8-12 ounces of a variety of seafood per week selected from choices lower in mercury.
“The FDA’s revised advice highlights the many nutrients found in fish, several of which have important roles in growth and development during pregnancy and early childhood. It also highlights the potential health benefits of eating fish as part of a healthy eating pattern, particularly for improving heart health and lowering the risk of obesity,” the press release states.
Despite these benefits – and the recommendations for intake – concerns about mercury in fish have led many pregnant women in the United States to consume far less than the recommended amount of seafood, according to Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition.
“Our goal is to make sure Americans are equipped with this knowledge so that they can reap the benefits of eating fish, while choosing types of fish that are safe for them and their families to eat,” Dr. Mayne said in the FDA statement.
In response to the revised guidance, John S. Cullen, MD, president of the American Academy of Family Physicians, said that all women should be counseled to eat a well-balanced and varied diet including meats, dairy products, fruits, vegetables, and grains, and pregnant women should limit their intake of fish and seafood products to 8-12 ounces, or about 2-3 fish meals, per week.
Pregnant women may eat salmon in moderation, but should avoid raw seafood of any type because of possible contamination with parasites and Norwalk-like viruses, he said, adding that seafood like shark, swordfish, king mackerel, tilefish, Bigeye (Ahi) tuna steaks, and other long-lived fish high on the food chain should be avoided completely because of high mercury levels.
“While the AAFP did not review the revised advice to the dietary guidelines, family physicians are on the front lines encouraging healthy nutrition for pregnant and breastfeeding women and young children. It’s an ongoing, important part of the patient-physician conversation that begins with the initial prenatal visit,” Dr. Cullen said in a statement.
Similarly, Christopher M. Zahn, MD, vice president of practice activities for the American College of Obstetricians and Gynecologists, said the FDA/EPA updated guidance is in line with ACOG recommendations.
“The guidance continues to underscore the value of eating seafood 2-3 times per week during pregnancy and the importance of avoiding fish products that are high in mercury. The additional emphasis on healthy eating patterns mirrors ACOG’s long-standing guidance on the importance of a well-balanced, varied, nutritional diet that is consistent with a woman’s access to food and food preferences,” he said in a statement, noting that “seafood is a nutrient-rich food that has proven beneficial to women and in aiding the development of a fetus throughout pregnancy.”
Tranexamic acid may not improve neurologic outcomes in patients with TBI
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
PHILADELPHIA – according to an investigation presented at the annual meeting of the American Academy of Neurology. For patients with TBI and intracranial hemorrhage (ICH), however, treatment with a 2-gram bolus of tranexamic acid within 42 minutes of injury significantly improves the rate of 28-day survival. Tranexamic acid therefore “is the first therapeutic with evidence for benefit in acute TBI,” said Susan Rowell, MD, trauma medical director at Duke University in Durham, North Carolina.
No effective treatment is available for TBI, which is a major cause of death after trauma. In 2010, the CRASH-2 trial (Lancet. 2010 Jul 03;376[9734]:23-32), suggested that tranexamic acid, a lysine analogue that decreases the breakdown of clots, safely reduced the rate of death from hemorrhage in patients with trauma and bleeding. Patients treated within 1 hour of injury were significantly more likely to survive than those treated at 1 hour or more after injury.
Two small, prospective trials failed to show that tranexamic acid reduced in-hospital mortality, improved neurologic function at discharge, or reduced the progression of ICH. A meta-analysis of both trials, however, showed a trend toward a benefit of treatment with this therapy.
A multicenter, prehospital trial
Dr. Rowell and colleagues hypothesized that prehospital administration of tranexamic acid to patients with moderate to severe TBI early after injury would increase the likelihood of a favorable neurologic outcome. Between March 2015 and March 2017, they enrolled 1,280 participants in a multicenter, prehospital trial. Eligible participants had moderate to severe TBI, were not in shock (as evidenced by a systolic blood pressure greater than 90 mm Hg before randomization), and were enrolled within 2 hours of injury.
Patients were randomized to one of three treatment arms and followed for 6 months. The first treatment arm received a 1-gram bolus of tranexamic acid before hospital admission and an 8-hour, 1-gram infusion of tranexamic acid in the hospital. The second arm received a 2-gram bolus of tranexamic acid before hospital admission and a placebo infusion in the hospital. The third arm received a placebo bolus and placebo infusion. Paramedics and participants were blinded to treatment assignment. The trial was conducted at 20 hospitals and 39 emergency medical services agencies in the United States and Canada.
The study’s primary outcome was functional neurologic outcome at 6 months, as measured by the Glasgow Outcomes Scale – Extended (GOSE). The investigators dichotomized results into favorable and poor categories. Other prespecified outcomes included early and late mortality, the disability rating scale (DRS), and progression of ICH.
Treatment was administered early
The researchers identified 1,280 eligible patients, of whom 1,063 were randomized. The modified intention-to-treat analysis included 309 participants in the placebo group, 312 in the bolus-maintenance group (the 1-gram group), and 345 in the bolus-only group (the 2-gram group). The population’s average age was approximately 42 years, and 75% of the sample was male. About half of the patients had a Glasgow Coma Scale score between 3 and 8. Injury severity and prehospital care were similar among the groups.
The researchers provided the drug infusion at an average of 0.7 hours (42 minutes) after injury, “which is actually quite early,” said Dr. Rowell. They observed few infusion-related deviations, and the entire bolus was infused in about 95% of patients. Approximately 70% of patients received the full 8-hour infusion. This result was influenced partly by stopping rules and by providers who requested unblinding to give open-label tranexamic acid. Overall, 57% of patients in the trial had an ICH on head CT, which was approximately the proportion that the researchers had anticipated.
Dr. Rowell and colleagues completed the 6-month follow-up for 85% of patients. They saw no difference in the 6-month neurologic outcome between the group of all patients who received tranexamic acid and those who received placebo. The investigators also saw no differences between groups in early and late mortality and the DRS.
About half of patients with ICH were evaluated for progression. Progression occurred in 20% of the placebo arm, 17% of the bolus-maintenance arm, and 15% of the bolus-only arm. The differences between groups were not statistically significant. Participants in the bolus-only group, however, were significantly less likely to die, compared with the placebo and the bolus-maintenance groups. The odds ratio of death for the bolus-only group, compared with the others, was about 0.5. The absolute mortality rate for the placebo and bolus-maintenance groups was 17%, compared with 12% for the bolus-only group. Most deaths were attributable to TBI, and few patients died of exsanguination.
In addition, the bolus-only group also had improved long-term neurologic outcome, as assessed by the 6-month DRS and the 6-month GOSE, compared with the bolus maintenance group.
Among patients with ICH, survival increased by approximately 12% at 10 hours after injury in the bolus-only group, compared with the bolus-maintenance and placebo groups. This difference persisted throughout the follow-up period, said Dr. Rowell.
Among predefined major adverse events, seizure-like activity occurred in 5% of the bolus-only group, compared with 2% of the placebo and bolus-maintenance groups. The researchers found no significant differences in any thrombotic event between the bolus-only group and the placebo group.
The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
SOURCE: Rowell S et al. AAN 2019, Abstract.
REPORTING FROM AAN 2019
Key clinical point: Early administration of tranexamic acid after TBI does not improve neurologic outcome at 6 months.
Major finding: Patients with TBI and ICH who received a 2-g bolus of tranexamic acid had a 50% lower rate of mortality.
Study details: A multicenter, prehospital trial that enrolled 1,063 patients with moderate to severe TBI.
Disclosures: The study was sponsored by University of Washington, Seattle. Collaborators included the National Heart, Lung, and Blood Institute; the U.S. Army Medical Research and Development Command; and the American Heart Association. Dr. Rowell had no relevant disclosures.
Source: Rowell S et al. AAN 2019, Abstract.