• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Resveratrol (trans-3,5,4’-trihydroxystilbene), a polyphenolic phytoalexin synthesized in nearly 70 plant species, is found to be particularly abundant in Vitis vinifera (grape vine) and its derivatives (e.g., red wine, purple grape juice), various berries, peanuts, jackfruit, pomegranate, eucalyptus, the roots of Polygonum cuspidatum (Japanese knotweed, which is used in traditional Chinese and Japanese medicine to treat dermatitis, among other conditions)¹, Scots pine, spruce, corn lily, gnetum, and butterfly orchid.^2-6 Several studies have demonstrated that resveratrol possesses potent antioxidant, anticarcinogenic, anti-inflammatory, as well as antimicrobial characteristics.^7-11 Specifically, in vitro and in vivo studies have shown that resveratrol exerts chemopreventive and antiproliferative activity against various cancers, including skin cancer, by suppressing cellular events associated with tumor initiation, promotion, and progression, and triggering apoptosis in such tumor cells.^12-14 It also is reputed to impart antiaging benefits.¹⁵ This column will focus on recent research findings pertaining to effects on the skin as well as topical uses of this botanical agent, the main source of which, V. vinifera, has been used since antiquity.

Resveratrol was first identified from the roots of Veratrum grandiflorum (white hellebore) in 1940,^16-19 but research on the compound did not take root until after a 1997 report in Science suggested chemopreventive properties. In that study, purified resveratrol was found to exhibit major inhibitory activity against cancer initiation, promotion, and progression.²⁰ Since then, copious research on this botanical compound has yielded a reputation as a strong antioxidant, anti-inflammatory, and antiproliferative agent.^7,21,22 Most importantly, resveratrol is considered to act as a chemopreventive agent against skin cancer and antiproliferative influence on oral squamous, breast, colon, and prostate cancer cells.^12,14 It is also one of the most studied polyphenolic compounds.

Skin cancer and photoprotection

In 2012, Osmond et al. conducted in vitro and in vivo experiments to assess the potential of resveratrol as a chemotherapy adjunct for melanoma treatment. Resveratrol significantly reduced melanoma cell viability in both melanoma cell lines tested, and selectively spared cells in the nonmalignant fibroblast lines, compared with its cytotoxic impact on melanoma cells. Further, cytotoxicity to malignant cells was greatly enhanced by 72 hours of treatment with resveratrol and temozolomide, compared with temozolomide treatment alone. No significant differences were seen in vivo. The researchers concluded that the in vitro antitumor activity of resveratrol suggested its potential as a therapeutic agent in melanoma management.²³

Resveratrol has been shown to protect against UVB-mediated cutaneous damage in SKH-1 hairless mice. Afaq et al. demonstrated that UVB-induced skin edema was significantly suppressed by the topical application of resveratrol to SKH-1 hairless mice.⁷

By Rj1979/ Wikimedia Commons/ public domain

In a different study by the same team, topically applied resveratrol significantly inhibited UVB-mediated increases in bifold skin thickness and edema and greatly diminished UVB-induced lipid peroxidation, cyclo-oxygenase and ornithine decarboxylase (ODC) activities, as well as protein expression of the ODC enzyme in SKH-1 hairless mice.²⁴ In an experiment by some of the same researchers, resveratrol was topically applied to SKH-1 hairless mice 30 minutes before exposure to UVB; 24 hours later, significant decreases were observed in bifold skin thickness, hyperplasia, and leukocyte infiltration. Critical cell cycle regulatory proteins, the target of the investigation, were substantially down-regulated because of the resveratrol. The investigators concluded that resveratrol might have the potential to play a significant role in preventing UVB-mediated photodamage and carcinogenesis.²⁵

More recently, in 2015, Sirerol et al. found that the topical treatment with pterostilbene, a natural dimethoxy analog of resveratrol, effectively shielded SKH-1 hairless mice from UVB-induced photodamage and carcinogenesis.²⁶

Interestingly, recent in vitro studies by Sticozzi and colleagues have shown that topical resveratrol dose-dependently protected human keratinocytes from cigarette smoke–induced reduction of scavenger receptor B1 protein expression²⁷ and can lower cigarette smoke–induced reactive oxygen species and carbonyl formation in human keratinocytes.²⁸

Antiaging activity

In 2010, Giardina et al. performed an in vitro study to evaluate the tonic-trophic characteristics of resveratrol alone and resveratrol plus N-acetyl-cysteine on cultured skin fibroblasts. Both formulations dose-dependently increased cell proliferation and inhibition of collagenase activity.²⁹

In 2012, Wu et al. investigated the protective effects of resveratrate, a stable derivative of resveratrol, against damage to human skin caused by repetitive solar simulator UV radiation (ssUVR) in 15 healthy human volunteers. Six sites on nonexposed dorsal skin of each participant were assessed, with four sites exposed to ssUVR and the remaining sites serving as positive control (ssUVR only) and baseline control (no treatment or exposure). The researchers noted minimal erythema on areas treated with resveratrate and the resveratrol derivative significantly inhibited sunburn cell formation. They concluded that resveratrate protects the skin against sunburn and suntan caused by repetitive ssUVR.⁴

Also that year, Buonocore et al. conducted a placebo-controlled, double-blind study in 50 subjects that revealed the antiaging efficacy of a dietary nutraceutical blend of resveratrol and procyanidin. Specifically, skin moisturization and elasticity improved while wrinkle depth and skin roughness lessened after 60 days of treatment.³⁰

In a 2013 in vitro study of the skin permeation kinetics of polyphenols using diffusion cells via ex vivo pig skin and a cellulose membrane, Zillich et al. showed that several polyphenols, including resveratrol, epigallocatechin gallate, quercetin, rutin, and protocatechuic acid formulated in oil-in-water emulsions could permeate the stratum corneum and were identified in the epidermis and dermis. The team concluded that their findings validate the use of polyphenols as active ingredients in antiaging products.³¹

In 2014, Farris et al. found that the topical application of resveratrol in a proprietary blend (1% resveratrol, 0.5% baicalin, 1% vitamin E) yielded a statistically significant amelioration of fine lines and wrinkles, hyperpigmentation, radiance, as well as skin roughness, firmness, elasticity, and laxity in a small study over 12 weeks.³²

Skin lightening

Resveratrol has also been used as a promising topical treatment for hyperpigmentation disorders.³³ The compound has been shown to work synergistically with 4-n-butylresorcinol (a derivative of resorcinol, one of the main phenols found in argan oil) to reduce tyrosinase levels and significantly diminish melanin synthesis, more effectively than either compound alone.³⁴ In 2012, Franco et al. observed that resveratrol can inhibit tyrosinase but it does not sufficiently suppress melanin production to justify its use as a lone skin-whitening agent in pharmaceutical formulations, but warrants attention as a coadjuvant for treating hyperpigmentation.³⁵ The skin-lightening capacity of resveratrol supported by a 2013 study in which 52 medicinal plants grown in Korea were tested for human tyrosinase activity and the dried stems of the grape tree V. vinifera were found to potently suppress human tyrosinase, and more effectively than arbutin.³⁶ It is worth noting that resveratrol, through its antioxidant activity and possible inhibitory effect on cytochrome P450 2E1 expression, has been shown to protect mouse primary hepatocytes from hydroquinone-induced cytotoxicity.³⁷ Also, J.M. Galgut and S.A. Ali, noted the gathering of pigment cells and resultant skin lightening from the effects of topical ethanolic extract of Arachis hypogaea (peanuts, which contain half the resveratrol of red wine) on the tail melanophores of tadpole Bufo melanostictus, concluding that resveratrol merits attention for potential clinical use as a nontoxic melanolytic agent to treat hyperpigmentation.^38,34

Acne

Resveratrol is considered an emerging agent in the topical armamentarium for treating acne.³⁹ In a single-blind pilot study in 2011, Fabbrocini et al. investigated the potential therapeutic impact of resveratrol on 20 patients with acne. A resveratrol-containing hydrogel was applied daily on the right side of the face for 60 days, with the left side receiving the hydrogel vehicle as control. No adverse effects were reported and all patients were satisfied with the treatment. Researchers reported a 53.75 % mean reduction in the Global Acne Grading System score on the resveratrol-treated sides and a 6.10 % decrease on the control sides. Histologic analysis revealed a statistically significant reduction of lesions in areas treated with resveratrol (66.7 % mean reduction in the average area of microcomedones on the resveratrol-treated sides vs. 9.7% reduction on the control sides).⁴⁰

A 2015 comprehensive literature review of randomized clinical trials and controlled trials by Dall’oglio et al. found that cosmetics with antimicrobial and anti-inflammatory ingredients, including resveratrol, may accelerate acne resolution.⁴¹

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

In a small 2013 study by Ferzli et al., 16 subjects with erythema applied a formulation containing resveratrol, green tea polyphenols, and caffeine twice daily to the whole face. Clinical photographs and spectrally enhanced images taken before treatment and every 2 weeks through 3 months were assessed. The investigators reported that improvement was seen in 16 of 16 clinical images and 13 of 16 spectrally enhanced images. Erythema reduction was observable by 6 weeks of treatment, and no adverse effects were observed.⁴³

Conclusion

Resveratrol is emerging as a compound with the potential to deliver significant health benefits, particularly in terms of photoprotective, cancer preventive, and cardioprotective activity. While there are 2 strong decades of research, more is necessary to elucidate the full potential of resveratrol as a first-line dermatologic therapy. Preclinical data do support the use of resveratrol in various product types (e.g., emollients, patches, sunscreens, and additional skin care products) intended to prevent skin cancer or to prevent or treat other conditions caused or exacerbated by solar exposure, such as photoaging. I look forward to seeing clinical evidence of the efficacy of topically applied resveratrol.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

References

1. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

2. Science. 1997 Jan 10;275(5297):218-20.

3. Cancer Res. 2001 Feb 15;61(4):1604-10.

4. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):345-50.

5. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21.

6. Dose Response. 2010 Mar 18;8(4):478-500.

7. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

8. Neoplasia. 2003 Jan-Feb;5(1):74-82.

9. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 108-9.)

10. Medical Herbalism: The Science and Practice of Herbal Medicine. (Rochester, Vt.: Healing Arts Press, 2003, pp. 99-100).

11. Eur J Pharm Sci. 2015 Oct 12;78:204-13.

12. Pancreas. 2002 Nov;25(4):e71-6.

13. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83.

14. J Biol Chem. 2003 Oct 17;278(42):41482-90.

15. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

16. Fitoterapia. 2013 Apr;86:84-91.

17. Ann N Y Acad Sci. 2011 Jan;1215:60-71.

18. Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):133-8.

19. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.

20. Science. 1997 Jan 10;275(5297):218-20.

21. Biochem Pharmacol. 2002 Jan 15:63(2):99-104.

22. Biomed Pap Med Fac univ Palacky Olomouc Czech Repub. 2003 Dec;147(2):137-45.

23. J Surg Res. 2012 Jan;172(1):109-15.

24. Front Biosci. 2002 Apr 1;7:d784-92.

25. Oncogene. 2004 Jul 1;23(30):5151-60.

26. Free Radic Biol Med. 2015 Aug;85:1-11.

27. Free Radic Biol Med. 2014 Apr;69:50-7.

28. Food Funct. 2014 Sep;5(9):2348-56.

29. Minerva Ginecol. 2010 Jun;62(3):195-201.

30. Clin Cosmet Investig Dermatol. 2012;5:159-65.

31. Int J Cosmet Sci. 2013 Oct;35(5):491-501.

32. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

33. Semin Cutan Med Surg. 2012 Jun;31(2):133-9.

34. Pharmazie. 2012 Jun;67(6):542-6.

35. Molecules. 2012 Oct 9;17(10):11816-25.

36. Evid Based Complement Alternat Med. 2013;2013:645257.

37. Int J Environ Res Public Health. 2012 Sep 19;9(9):3354-64.

38. J Recept Signal Transduct Res. 2011 Oct;31(5):374-80.

39. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

40. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.

41. G Ital Dermatol Venereol. 2015 Feb;150(1):1-11.

42. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96.

43. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.

• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Resveratrol (trans-3,5,4’-trihydroxystilbene), a polyphenolic phytoalexin synthesized in nearly 70 plant species, is found to be particularly abundant in Vitis vinifera (grape vine) and its derivatives (e.g., red wine, purple grape juice), various berries, peanuts, jackfruit, pomegranate, eucalyptus, the roots of Polygonum cuspidatum (Japanese knotweed, which is used in traditional Chinese and Japanese medicine to treat dermatitis, among other conditions)¹, Scots pine, spruce, corn lily, gnetum, and butterfly orchid.^2-6 Several studies have demonstrated that resveratrol possesses potent antioxidant, anticarcinogenic, anti-inflammatory, as well as antimicrobial characteristics.^7-11 Specifically, in vitro and in vivo studies have shown that resveratrol exerts chemopreventive and antiproliferative activity against various cancers, including skin cancer, by suppressing cellular events associated with tumor initiation, promotion, and progression, and triggering apoptosis in such tumor cells.^12-14 It also is reputed to impart antiaging benefits.¹⁵ This column will focus on recent research findings pertaining to effects on the skin as well as topical uses of this botanical agent, the main source of which, V. vinifera, has been used since antiquity.

Resveratrol was first identified from the roots of Veratrum grandiflorum (white hellebore) in 1940,^16-19 but research on the compound did not take root until after a 1997 report in Science suggested chemopreventive properties. In that study, purified resveratrol was found to exhibit major inhibitory activity against cancer initiation, promotion, and progression.²⁰ Since then, copious research on this botanical compound has yielded a reputation as a strong antioxidant, anti-inflammatory, and antiproliferative agent.^7,21,22 Most importantly, resveratrol is considered to act as a chemopreventive agent against skin cancer and antiproliferative influence on oral squamous, breast, colon, and prostate cancer cells.^12,14 It is also one of the most studied polyphenolic compounds.

Skin cancer and photoprotection

In 2012, Osmond et al. conducted in vitro and in vivo experiments to assess the potential of resveratrol as a chemotherapy adjunct for melanoma treatment. Resveratrol significantly reduced melanoma cell viability in both melanoma cell lines tested, and selectively spared cells in the nonmalignant fibroblast lines, compared with its cytotoxic impact on melanoma cells. Further, cytotoxicity to malignant cells was greatly enhanced by 72 hours of treatment with resveratrol and temozolomide, compared with temozolomide treatment alone. No significant differences were seen in vivo. The researchers concluded that the in vitro antitumor activity of resveratrol suggested its potential as a therapeutic agent in melanoma management.²³

Resveratrol has been shown to protect against UVB-mediated cutaneous damage in SKH-1 hairless mice. Afaq et al. demonstrated that UVB-induced skin edema was significantly suppressed by the topical application of resveratrol to SKH-1 hairless mice.⁷

By Rj1979/ Wikimedia Commons/ public domain

In a different study by the same team, topically applied resveratrol significantly inhibited UVB-mediated increases in bifold skin thickness and edema and greatly diminished UVB-induced lipid peroxidation, cyclo-oxygenase and ornithine decarboxylase (ODC) activities, as well as protein expression of the ODC enzyme in SKH-1 hairless mice.²⁴ In an experiment by some of the same researchers, resveratrol was topically applied to SKH-1 hairless mice 30 minutes before exposure to UVB; 24 hours later, significant decreases were observed in bifold skin thickness, hyperplasia, and leukocyte infiltration. Critical cell cycle regulatory proteins, the target of the investigation, were substantially down-regulated because of the resveratrol. The investigators concluded that resveratrol might have the potential to play a significant role in preventing UVB-mediated photodamage and carcinogenesis.²⁵

More recently, in 2015, Sirerol et al. found that the topical treatment with pterostilbene, a natural dimethoxy analog of resveratrol, effectively shielded SKH-1 hairless mice from UVB-induced photodamage and carcinogenesis.²⁶

Interestingly, recent in vitro studies by Sticozzi and colleagues have shown that topical resveratrol dose-dependently protected human keratinocytes from cigarette smoke–induced reduction of scavenger receptor B1 protein expression²⁷ and can lower cigarette smoke–induced reactive oxygen species and carbonyl formation in human keratinocytes.²⁸

Antiaging activity

In 2010, Giardina et al. performed an in vitro study to evaluate the tonic-trophic characteristics of resveratrol alone and resveratrol plus N-acetyl-cysteine on cultured skin fibroblasts. Both formulations dose-dependently increased cell proliferation and inhibition of collagenase activity.²⁹

In 2012, Wu et al. investigated the protective effects of resveratrate, a stable derivative of resveratrol, against damage to human skin caused by repetitive solar simulator UV radiation (ssUVR) in 15 healthy human volunteers. Six sites on nonexposed dorsal skin of each participant were assessed, with four sites exposed to ssUVR and the remaining sites serving as positive control (ssUVR only) and baseline control (no treatment or exposure). The researchers noted minimal erythema on areas treated with resveratrate and the resveratrol derivative significantly inhibited sunburn cell formation. They concluded that resveratrate protects the skin against sunburn and suntan caused by repetitive ssUVR.⁴

Also that year, Buonocore et al. conducted a placebo-controlled, double-blind study in 50 subjects that revealed the antiaging efficacy of a dietary nutraceutical blend of resveratrol and procyanidin. Specifically, skin moisturization and elasticity improved while wrinkle depth and skin roughness lessened after 60 days of treatment.³⁰

In a 2013 in vitro study of the skin permeation kinetics of polyphenols using diffusion cells via ex vivo pig skin and a cellulose membrane, Zillich et al. showed that several polyphenols, including resveratrol, epigallocatechin gallate, quercetin, rutin, and protocatechuic acid formulated in oil-in-water emulsions could permeate the stratum corneum and were identified in the epidermis and dermis. The team concluded that their findings validate the use of polyphenols as active ingredients in antiaging products.³¹

In 2014, Farris et al. found that the topical application of resveratrol in a proprietary blend (1% resveratrol, 0.5% baicalin, 1% vitamin E) yielded a statistically significant amelioration of fine lines and wrinkles, hyperpigmentation, radiance, as well as skin roughness, firmness, elasticity, and laxity in a small study over 12 weeks.³²

Skin lightening

Resveratrol has also been used as a promising topical treatment for hyperpigmentation disorders.³³ The compound has been shown to work synergistically with 4-n-butylresorcinol (a derivative of resorcinol, one of the main phenols found in argan oil) to reduce tyrosinase levels and significantly diminish melanin synthesis, more effectively than either compound alone.³⁴ In 2012, Franco et al. observed that resveratrol can inhibit tyrosinase but it does not sufficiently suppress melanin production to justify its use as a lone skin-whitening agent in pharmaceutical formulations, but warrants attention as a coadjuvant for treating hyperpigmentation.³⁵ The skin-lightening capacity of resveratrol supported by a 2013 study in which 52 medicinal plants grown in Korea were tested for human tyrosinase activity and the dried stems of the grape tree V. vinifera were found to potently suppress human tyrosinase, and more effectively than arbutin.³⁶ It is worth noting that resveratrol, through its antioxidant activity and possible inhibitory effect on cytochrome P450 2E1 expression, has been shown to protect mouse primary hepatocytes from hydroquinone-induced cytotoxicity.³⁷ Also, J.M. Galgut and S.A. Ali, noted the gathering of pigment cells and resultant skin lightening from the effects of topical ethanolic extract of Arachis hypogaea (peanuts, which contain half the resveratrol of red wine) on the tail melanophores of tadpole Bufo melanostictus, concluding that resveratrol merits attention for potential clinical use as a nontoxic melanolytic agent to treat hyperpigmentation.^38,34

Acne

Resveratrol is considered an emerging agent in the topical armamentarium for treating acne.³⁹ In a single-blind pilot study in 2011, Fabbrocini et al. investigated the potential therapeutic impact of resveratrol on 20 patients with acne. A resveratrol-containing hydrogel was applied daily on the right side of the face for 60 days, with the left side receiving the hydrogel vehicle as control. No adverse effects were reported and all patients were satisfied with the treatment. Researchers reported a 53.75 % mean reduction in the Global Acne Grading System score on the resveratrol-treated sides and a 6.10 % decrease on the control sides. Histologic analysis revealed a statistically significant reduction of lesions in areas treated with resveratrol (66.7 % mean reduction in the average area of microcomedones on the resveratrol-treated sides vs. 9.7% reduction on the control sides).⁴⁰

A 2015 comprehensive literature review of randomized clinical trials and controlled trials by Dall’oglio et al. found that cosmetics with antimicrobial and anti-inflammatory ingredients, including resveratrol, may accelerate acne resolution.⁴¹

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

In a small 2013 study by Ferzli et al., 16 subjects with erythema applied a formulation containing resveratrol, green tea polyphenols, and caffeine twice daily to the whole face. Clinical photographs and spectrally enhanced images taken before treatment and every 2 weeks through 3 months were assessed. The investigators reported that improvement was seen in 16 of 16 clinical images and 13 of 16 spectrally enhanced images. Erythema reduction was observable by 6 weeks of treatment, and no adverse effects were observed.⁴³

Conclusion

Resveratrol is emerging as a compound with the potential to deliver significant health benefits, particularly in terms of photoprotective, cancer preventive, and cardioprotective activity. While there are 2 strong decades of research, more is necessary to elucidate the full potential of resveratrol as a first-line dermatologic therapy. Preclinical data do support the use of resveratrol in various product types (e.g., emollients, patches, sunscreens, and additional skin care products) intended to prevent skin cancer or to prevent or treat other conditions caused or exacerbated by solar exposure, such as photoaging. I look forward to seeing clinical evidence of the efficacy of topically applied resveratrol.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

References

1. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

2. Science. 1997 Jan 10;275(5297):218-20.

3. Cancer Res. 2001 Feb 15;61(4):1604-10.

4. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):345-50.

5. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21.

6. Dose Response. 2010 Mar 18;8(4):478-500.

7. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

8. Neoplasia. 2003 Jan-Feb;5(1):74-82.

9. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 108-9.)

10. Medical Herbalism: The Science and Practice of Herbal Medicine. (Rochester, Vt.: Healing Arts Press, 2003, pp. 99-100).

11. Eur J Pharm Sci. 2015 Oct 12;78:204-13.

12. Pancreas. 2002 Nov;25(4):e71-6.

13. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83.

14. J Biol Chem. 2003 Oct 17;278(42):41482-90.

15. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

16. Fitoterapia. 2013 Apr;86:84-91.

17. Ann N Y Acad Sci. 2011 Jan;1215:60-71.

18. Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):133-8.

19. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.

20. Science. 1997 Jan 10;275(5297):218-20.

21. Biochem Pharmacol. 2002 Jan 15:63(2):99-104.

22. Biomed Pap Med Fac univ Palacky Olomouc Czech Repub. 2003 Dec;147(2):137-45.

23. J Surg Res. 2012 Jan;172(1):109-15.

24. Front Biosci. 2002 Apr 1;7:d784-92.

25. Oncogene. 2004 Jul 1;23(30):5151-60.

26. Free Radic Biol Med. 2015 Aug;85:1-11.

27. Free Radic Biol Med. 2014 Apr;69:50-7.

28. Food Funct. 2014 Sep;5(9):2348-56.

29. Minerva Ginecol. 2010 Jun;62(3):195-201.

30. Clin Cosmet Investig Dermatol. 2012;5:159-65.

31. Int J Cosmet Sci. 2013 Oct;35(5):491-501.

32. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

33. Semin Cutan Med Surg. 2012 Jun;31(2):133-9.

34. Pharmazie. 2012 Jun;67(6):542-6.

35. Molecules. 2012 Oct 9;17(10):11816-25.

36. Evid Based Complement Alternat Med. 2013;2013:645257.

37. Int J Environ Res Public Health. 2012 Sep 19;9(9):3354-64.

38. J Recept Signal Transduct Res. 2011 Oct;31(5):374-80.

39. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

40. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.

41. G Ital Dermatol Venereol. 2015 Feb;150(1):1-11.

42. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96.

43. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.

• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Resveratrol (trans-3,5,4’-trihydroxystilbene), a polyphenolic phytoalexin synthesized in nearly 70 plant species, is found to be particularly abundant in Vitis vinifera (grape vine) and its derivatives (e.g., red wine, purple grape juice), various berries, peanuts, jackfruit, pomegranate, eucalyptus, the roots of Polygonum cuspidatum (Japanese knotweed, which is used in traditional Chinese and Japanese medicine to treat dermatitis, among other conditions)¹, Scots pine, spruce, corn lily, gnetum, and butterfly orchid.^2-6 Several studies have demonstrated that resveratrol possesses potent antioxidant, anticarcinogenic, anti-inflammatory, as well as antimicrobial characteristics.^7-11 Specifically, in vitro and in vivo studies have shown that resveratrol exerts chemopreventive and antiproliferative activity against various cancers, including skin cancer, by suppressing cellular events associated with tumor initiation, promotion, and progression, and triggering apoptosis in such tumor cells.^12-14 It also is reputed to impart antiaging benefits.¹⁵ This column will focus on recent research findings pertaining to effects on the skin as well as topical uses of this botanical agent, the main source of which, V. vinifera, has been used since antiquity.

Resveratrol was first identified from the roots of Veratrum grandiflorum (white hellebore) in 1940,^16-19 but research on the compound did not take root until after a 1997 report in Science suggested chemopreventive properties. In that study, purified resveratrol was found to exhibit major inhibitory activity against cancer initiation, promotion, and progression.²⁰ Since then, copious research on this botanical compound has yielded a reputation as a strong antioxidant, anti-inflammatory, and antiproliferative agent.^7,21,22 Most importantly, resveratrol is considered to act as a chemopreventive agent against skin cancer and antiproliferative influence on oral squamous, breast, colon, and prostate cancer cells.^12,14 It is also one of the most studied polyphenolic compounds.

Skin cancer and photoprotection

In 2012, Osmond et al. conducted in vitro and in vivo experiments to assess the potential of resveratrol as a chemotherapy adjunct for melanoma treatment. Resveratrol significantly reduced melanoma cell viability in both melanoma cell lines tested, and selectively spared cells in the nonmalignant fibroblast lines, compared with its cytotoxic impact on melanoma cells. Further, cytotoxicity to malignant cells was greatly enhanced by 72 hours of treatment with resveratrol and temozolomide, compared with temozolomide treatment alone. No significant differences were seen in vivo. The researchers concluded that the in vitro antitumor activity of resveratrol suggested its potential as a therapeutic agent in melanoma management.²³

Resveratrol has been shown to protect against UVB-mediated cutaneous damage in SKH-1 hairless mice. Afaq et al. demonstrated that UVB-induced skin edema was significantly suppressed by the topical application of resveratrol to SKH-1 hairless mice.⁷

By Rj1979/ Wikimedia Commons/ public domain

In a different study by the same team, topically applied resveratrol significantly inhibited UVB-mediated increases in bifold skin thickness and edema and greatly diminished UVB-induced lipid peroxidation, cyclo-oxygenase and ornithine decarboxylase (ODC) activities, as well as protein expression of the ODC enzyme in SKH-1 hairless mice.²⁴ In an experiment by some of the same researchers, resveratrol was topically applied to SKH-1 hairless mice 30 minutes before exposure to UVB; 24 hours later, significant decreases were observed in bifold skin thickness, hyperplasia, and leukocyte infiltration. Critical cell cycle regulatory proteins, the target of the investigation, were substantially down-regulated because of the resveratrol. The investigators concluded that resveratrol might have the potential to play a significant role in preventing UVB-mediated photodamage and carcinogenesis.²⁵

More recently, in 2015, Sirerol et al. found that the topical treatment with pterostilbene, a natural dimethoxy analog of resveratrol, effectively shielded SKH-1 hairless mice from UVB-induced photodamage and carcinogenesis.²⁶

Interestingly, recent in vitro studies by Sticozzi and colleagues have shown that topical resveratrol dose-dependently protected human keratinocytes from cigarette smoke–induced reduction of scavenger receptor B1 protein expression²⁷ and can lower cigarette smoke–induced reactive oxygen species and carbonyl formation in human keratinocytes.²⁸

Antiaging activity

In 2010, Giardina et al. performed an in vitro study to evaluate the tonic-trophic characteristics of resveratrol alone and resveratrol plus N-acetyl-cysteine on cultured skin fibroblasts. Both formulations dose-dependently increased cell proliferation and inhibition of collagenase activity.²⁹

In 2012, Wu et al. investigated the protective effects of resveratrate, a stable derivative of resveratrol, against damage to human skin caused by repetitive solar simulator UV radiation (ssUVR) in 15 healthy human volunteers. Six sites on nonexposed dorsal skin of each participant were assessed, with four sites exposed to ssUVR and the remaining sites serving as positive control (ssUVR only) and baseline control (no treatment or exposure). The researchers noted minimal erythema on areas treated with resveratrate and the resveratrol derivative significantly inhibited sunburn cell formation. They concluded that resveratrate protects the skin against sunburn and suntan caused by repetitive ssUVR.⁴

Also that year, Buonocore et al. conducted a placebo-controlled, double-blind study in 50 subjects that revealed the antiaging efficacy of a dietary nutraceutical blend of resveratrol and procyanidin. Specifically, skin moisturization and elasticity improved while wrinkle depth and skin roughness lessened after 60 days of treatment.³⁰

In a 2013 in vitro study of the skin permeation kinetics of polyphenols using diffusion cells via ex vivo pig skin and a cellulose membrane, Zillich et al. showed that several polyphenols, including resveratrol, epigallocatechin gallate, quercetin, rutin, and protocatechuic acid formulated in oil-in-water emulsions could permeate the stratum corneum and were identified in the epidermis and dermis. The team concluded that their findings validate the use of polyphenols as active ingredients in antiaging products.³¹

In 2014, Farris et al. found that the topical application of resveratrol in a proprietary blend (1% resveratrol, 0.5% baicalin, 1% vitamin E) yielded a statistically significant amelioration of fine lines and wrinkles, hyperpigmentation, radiance, as well as skin roughness, firmness, elasticity, and laxity in a small study over 12 weeks.³²

Skin lightening

Resveratrol has also been used as a promising topical treatment for hyperpigmentation disorders.³³ The compound has been shown to work synergistically with 4-n-butylresorcinol (a derivative of resorcinol, one of the main phenols found in argan oil) to reduce tyrosinase levels and significantly diminish melanin synthesis, more effectively than either compound alone.³⁴ In 2012, Franco et al. observed that resveratrol can inhibit tyrosinase but it does not sufficiently suppress melanin production to justify its use as a lone skin-whitening agent in pharmaceutical formulations, but warrants attention as a coadjuvant for treating hyperpigmentation.³⁵ The skin-lightening capacity of resveratrol supported by a 2013 study in which 52 medicinal plants grown in Korea were tested for human tyrosinase activity and the dried stems of the grape tree V. vinifera were found to potently suppress human tyrosinase, and more effectively than arbutin.³⁶ It is worth noting that resveratrol, through its antioxidant activity and possible inhibitory effect on cytochrome P450 2E1 expression, has been shown to protect mouse primary hepatocytes from hydroquinone-induced cytotoxicity.³⁷ Also, J.M. Galgut and S.A. Ali, noted the gathering of pigment cells and resultant skin lightening from the effects of topical ethanolic extract of Arachis hypogaea (peanuts, which contain half the resveratrol of red wine) on the tail melanophores of tadpole Bufo melanostictus, concluding that resveratrol merits attention for potential clinical use as a nontoxic melanolytic agent to treat hyperpigmentation.^38,34

Acne

Resveratrol is considered an emerging agent in the topical armamentarium for treating acne.³⁹ In a single-blind pilot study in 2011, Fabbrocini et al. investigated the potential therapeutic impact of resveratrol on 20 patients with acne. A resveratrol-containing hydrogel was applied daily on the right side of the face for 60 days, with the left side receiving the hydrogel vehicle as control. No adverse effects were reported and all patients were satisfied with the treatment. Researchers reported a 53.75 % mean reduction in the Global Acne Grading System score on the resveratrol-treated sides and a 6.10 % decrease on the control sides. Histologic analysis revealed a statistically significant reduction of lesions in areas treated with resveratrol (66.7 % mean reduction in the average area of microcomedones on the resveratrol-treated sides vs. 9.7% reduction on the control sides).⁴⁰

A 2015 comprehensive literature review of randomized clinical trials and controlled trials by Dall’oglio et al. found that cosmetics with antimicrobial and anti-inflammatory ingredients, including resveratrol, may accelerate acne resolution.⁴¹

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

In a small 2013 study by Ferzli et al., 16 subjects with erythema applied a formulation containing resveratrol, green tea polyphenols, and caffeine twice daily to the whole face. Clinical photographs and spectrally enhanced images taken before treatment and every 2 weeks through 3 months were assessed. The investigators reported that improvement was seen in 16 of 16 clinical images and 13 of 16 spectrally enhanced images. Erythema reduction was observable by 6 weeks of treatment, and no adverse effects were observed.⁴³

Conclusion

Resveratrol is emerging as a compound with the potential to deliver significant health benefits, particularly in terms of photoprotective, cancer preventive, and cardioprotective activity. While there are 2 strong decades of research, more is necessary to elucidate the full potential of resveratrol as a first-line dermatologic therapy. Preclinical data do support the use of resveratrol in various product types (e.g., emollients, patches, sunscreens, and additional skin care products) intended to prevent skin cancer or to prevent or treat other conditions caused or exacerbated by solar exposure, such as photoaging. I look forward to seeing clinical evidence of the efficacy of topically applied resveratrol.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

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LONDON—Strong evidence suggests an association between pediatric CNS demyelinating diseases and psychiatric disorders, according to a population-based study presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Mental health professionals need to be involved early with patients with MS as part of a multidisciplinary care approach, said the researchers.

In adults, MS is associated with various psychiatric disorders. When MS onset occurs in children, particularly when the pathophysiology occurs during a key period of CNS development, MS may be associated with a different set of psychiatric disorders, compared with those in adults.

To assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa, Julia Pakpoor, academic and clinical trainee at the University of Oxford in the United Kingdom, and colleagues analyzed linked English Hospital Episode Statistics and mortality data for the years 1999 to 2011. Cohorts were constructed of children (ie, patients younger than 18) admitted with MS and other CNS demyelinating diseases. The investigators searched for any subsequent episode of care with psychiatric disorders in these cohorts, and compared them to a reference cohort.

The researchers included 201 children in the MS cohort, 1,097 children in the CNS demyelinating-diseases cohort, and more than 1.1 million children in the reference cohort. Children with a demyelinating disease had an increased risk of psychotic disorders (standardized rate ratio [RR] 5.77); anxiety, stress-related, and somatoform disorders (RR, 2.38); intellectual disability (RR, 6.56); and other behavioral disorders (RR, 8.99), as well as an elevated rate of any of the psychiatric disorders studied (RR, 1.56). These findings remained significant with a one-year minimum interval between the first demyelinating disease episode and the first psychiatric disorder episode. They remained significant for psychotic disorders, intellectual disability, and other behavioral disorders with a minimum five-year interval.

In an analysis of the pediatric MS cohort as the exposure, the researchers observed elevated rates of psychotic disorders (RR, 10.76), mood disorders (RR, 2.57), and intellectual disability (RR, 6.08). In reverse analyses, the researchers found elevated rates of demyelinating diseases after anxiety, stress-related, and somatoform disorders (RR, 3.15); ADHD (RR, 3.88); autism (RR, 3.80); intellectual disability (RR, 6.33); other behavioral disorders (RR, 8.30); and any of the psychiatric disorders studied (RR, 2.15).

“What this study and what many other studies of comorbidities in MS demonstrate is that it’s high time to abandon the single-disease approach, which has perhaps been the approach for a long time not only in medical research, but also medical care and medical education,” said Ms. Pakpoor. “What we clearly need to do is develop more comprehensive algorithms to identify psychiatric comorbidities for a broad range of these individuals.”

—Erik Greb

LONDON—Strong evidence suggests an association between pediatric CNS demyelinating diseases and psychiatric disorders, according to a population-based study presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Mental health professionals need to be involved early with patients with MS as part of a multidisciplinary care approach, said the researchers.

In adults, MS is associated with various psychiatric disorders. When MS onset occurs in children, particularly when the pathophysiology occurs during a key period of CNS development, MS may be associated with a different set of psychiatric disorders, compared with those in adults.

To assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa, Julia Pakpoor, academic and clinical trainee at the University of Oxford in the United Kingdom, and colleagues analyzed linked English Hospital Episode Statistics and mortality data for the years 1999 to 2011. Cohorts were constructed of children (ie, patients younger than 18) admitted with MS and other CNS demyelinating diseases. The investigators searched for any subsequent episode of care with psychiatric disorders in these cohorts, and compared them to a reference cohort.

The researchers included 201 children in the MS cohort, 1,097 children in the CNS demyelinating-diseases cohort, and more than 1.1 million children in the reference cohort. Children with a demyelinating disease had an increased risk of psychotic disorders (standardized rate ratio [RR] 5.77); anxiety, stress-related, and somatoform disorders (RR, 2.38); intellectual disability (RR, 6.56); and other behavioral disorders (RR, 8.99), as well as an elevated rate of any of the psychiatric disorders studied (RR, 1.56). These findings remained significant with a one-year minimum interval between the first demyelinating disease episode and the first psychiatric disorder episode. They remained significant for psychotic disorders, intellectual disability, and other behavioral disorders with a minimum five-year interval.

In an analysis of the pediatric MS cohort as the exposure, the researchers observed elevated rates of psychotic disorders (RR, 10.76), mood disorders (RR, 2.57), and intellectual disability (RR, 6.08). In reverse analyses, the researchers found elevated rates of demyelinating diseases after anxiety, stress-related, and somatoform disorders (RR, 3.15); ADHD (RR, 3.88); autism (RR, 3.80); intellectual disability (RR, 6.33); other behavioral disorders (RR, 8.30); and any of the psychiatric disorders studied (RR, 2.15).

“What this study and what many other studies of comorbidities in MS demonstrate is that it’s high time to abandon the single-disease approach, which has perhaps been the approach for a long time not only in medical research, but also medical care and medical education,” said Ms. Pakpoor. “What we clearly need to do is develop more comprehensive algorithms to identify psychiatric comorbidities for a broad range of these individuals.”

—Erik Greb

LONDON—Strong evidence suggests an association between pediatric CNS demyelinating diseases and psychiatric disorders, according to a population-based study presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Mental health professionals need to be involved early with patients with MS as part of a multidisciplinary care approach, said the researchers.

In adults, MS is associated with various psychiatric disorders. When MS onset occurs in children, particularly when the pathophysiology occurs during a key period of CNS development, MS may be associated with a different set of psychiatric disorders, compared with those in adults.

To assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa, Julia Pakpoor, academic and clinical trainee at the University of Oxford in the United Kingdom, and colleagues analyzed linked English Hospital Episode Statistics and mortality data for the years 1999 to 2011. Cohorts were constructed of children (ie, patients younger than 18) admitted with MS and other CNS demyelinating diseases. The investigators searched for any subsequent episode of care with psychiatric disorders in these cohorts, and compared them to a reference cohort.

The researchers included 201 children in the MS cohort, 1,097 children in the CNS demyelinating-diseases cohort, and more than 1.1 million children in the reference cohort. Children with a demyelinating disease had an increased risk of psychotic disorders (standardized rate ratio [RR] 5.77); anxiety, stress-related, and somatoform disorders (RR, 2.38); intellectual disability (RR, 6.56); and other behavioral disorders (RR, 8.99), as well as an elevated rate of any of the psychiatric disorders studied (RR, 1.56). These findings remained significant with a one-year minimum interval between the first demyelinating disease episode and the first psychiatric disorder episode. They remained significant for psychotic disorders, intellectual disability, and other behavioral disorders with a minimum five-year interval.

In an analysis of the pediatric MS cohort as the exposure, the researchers observed elevated rates of psychotic disorders (RR, 10.76), mood disorders (RR, 2.57), and intellectual disability (RR, 6.08). In reverse analyses, the researchers found elevated rates of demyelinating diseases after anxiety, stress-related, and somatoform disorders (RR, 3.15); ADHD (RR, 3.88); autism (RR, 3.80); intellectual disability (RR, 6.33); other behavioral disorders (RR, 8.30); and any of the psychiatric disorders studied (RR, 2.15).

“What this study and what many other studies of comorbidities in MS demonstrate is that it’s high time to abandon the single-disease approach, which has perhaps been the approach for a long time not only in medical research, but also medical care and medical education,” said Ms. Pakpoor. “What we clearly need to do is develop more comprehensive algorithms to identify psychiatric comorbidities for a broad range of these individuals.”

—Erik Greb

Even with the clock ticking on the current election year, President Barak Obama and Congress appear ready to begin implementing at least some of the Commission on Care recommendations. In Senate and House of Representatives committee meetings over the past 2 weeks, a consensus has emerged to implement most of the Commission’s 18 recommendations. Still, most action is expected to take place after the November election, which will change who is in the White House and also could affect leadership within the VA as well as the House and Senate veteran oversight committees.

Currently 22% of veteran appointments are in community settings and the VA has already seen 5 million appointments through the Veterans Choice Program. Still, as VA Secretary Robert A. McDonald told the Senate committee on Wednesday, just 5,000 veterans are using community care only, which McDonald argued was evidence of veterans' strong desire to continue receiving VA care. The Veterans Choice Program is currently scheduled to expire August 7, 2017.  

“I strongly support the Commission's principle that creating a high-performing, integrated health care system that encompasses both VA and private care is critical to serving the needs of veterans,” President Obama said in a letter to the House Committee on Veterans Affairs. “It is critical that we preserve and continue to improve the VA health care system and ensure that VA has the ability to serve veterans.” The President also emphasized the importance of preserving the high quality of VA care, noting, “VA also provides unique, highly specialized care for many medical conditions, such as spinal cord and traumatic brain injuries, which are simply not available to the same extent outside of VA.”

“In our view that VHA must change, and change profoundly, because veterans deserve a better organized, high-performing health care system,” Nancy Schlichting, Commission on Care chairperson told the House committee. “Certainly, some elements of such a high-performing system are already in place. VA has high-quality clinical staff, and this integrated health care system is marked by good care-coordination. VHA today, however, relies significantly on community providers to augment the care it provides directly, although those community partners are not part of a cohesive system.”

According to Schlichting, fixing access issues “cannot be achieved by ‘tweaking’ existing programs or mounting a complex new delivery framework on a weak infrastructure platform.” Instead, the Commission recommended the creation of integrated systems approach to the VA that would re-engineer VA’s fundamental internal systems, both in terms of how it delivers health care as well as the technology it uses.

Veteran service organizations weighed in with cautious approval of many of the Commission’s recommendations, especially those that improved oversight, governance, and access to care, but cautioned against privatizing the VA.

“After two years of spirited and passionate debate about the future of veterans health care, we envision a clear path forward that builds on the strengths of the existing VA system, while expanding access by seamlessly integrating the best of community care to ensure no veteran must travel too far or wait too long for care,” Joy J. Ilem, national legislative director of Disabled American Veterans wrote in a letter submitted to the House committee. “Congress and VA must now begin the steps to finalize plans and move forward with the evolution of veterans health care.”

Despite the emerging consensus, a number of voices expressed concern about the impact of the Commission on Care’s proposals changes. A group of unions and professional organizations that represent VA employees (Association of VA Psychologist Leaders, Association of VA Social Workers, Nurses Organization of Veterans Affairs, Veterans Affairs Physician Assistant Association, American Federation of Government Employees, National Federation of Federal Employees, National Association of Government Employees, National Nurses United, the American Psychological Association, and National Association of Social Workers) expressed its concerns in a letter submitted to the House panel. “As organizations comprised of and representing health care practitioners, researchers, educators, administrators and personnel devoted to serving veterans, we have serious reservations about the report’s major recommendation to replace the current VHA with a new entity, to be known as the VHA Care System.” The letter argues that the proposed VHA Care System “disassembles one of the most effective, innovative features of current VHA care—the Primary Care/Mental Health Integration approach.”

In his Senate testimony, Secretary McDonald also expressed concern with the potential cost of some of the Commission on Care proposals. Currently the VA is spending  $13.5 billion in community care. According to McDonald, the VA would need $17 billion to make the upgrades it outlined in its October Plan to Consolidate Community Care, but he warned “the Commission on Care plan would be much more expensive than that.” More importantly, McDonald insisted, the VA should retain primary responsibility for the care of veterans. "We believe the VA needs to be the care coordinator," he insisted.

Another concern echoed by many of the commenters was the proposal to create an oversight board to provide governance, set long-term strategy, and direct and oversee reform. According to its critics, the proposal not only would undermine the authority of VA leadership, but could reduce congressional oversight as well. “NOVA strongly opposes giving an outside board—made up of civilian health care executives who may have never set foot into a VA facility—the authority to make decisions about the care and services provided America’s veterans,” argued Sharon Johnson, MSN, RN, president of the Nurses Organization of Veteran Affairs.

Mark Takata (D-Calif.) the ranking minority member of the House committee also expressed concern that the changes could impact VA clinicians’ access to high quality research, and clinician training. “The Commission on Care recommendations might in fact weaken the VA health care system,” Takata argued. “Proposals to funnels funding to private contractors and for profit care will take desperately needed resources away from our veterans and should be immediately rejected.... We cannot view expanded choice or the private sector as the panacea for solving the challenges the VA faces.”

Even with the clock ticking on the current election year, President Barak Obama and Congress appear ready to begin implementing at least some of the Commission on Care recommendations. In Senate and House of Representatives committee meetings over the past 2 weeks, a consensus has emerged to implement most of the Commission’s 18 recommendations. Still, most action is expected to take place after the November election, which will change who is in the White House and also could affect leadership within the VA as well as the House and Senate veteran oversight committees.

Currently 22% of veteran appointments are in community settings and the VA has already seen 5 million appointments through the Veterans Choice Program. Still, as VA Secretary Robert A. McDonald told the Senate committee on Wednesday, just 5,000 veterans are using community care only, which McDonald argued was evidence of veterans' strong desire to continue receiving VA care. The Veterans Choice Program is currently scheduled to expire August 7, 2017.  

“I strongly support the Commission's principle that creating a high-performing, integrated health care system that encompasses both VA and private care is critical to serving the needs of veterans,” President Obama said in a letter to the House Committee on Veterans Affairs. “It is critical that we preserve and continue to improve the VA health care system and ensure that VA has the ability to serve veterans.” The President also emphasized the importance of preserving the high quality of VA care, noting, “VA also provides unique, highly specialized care for many medical conditions, such as spinal cord and traumatic brain injuries, which are simply not available to the same extent outside of VA.”

“In our view that VHA must change, and change profoundly, because veterans deserve a better organized, high-performing health care system,” Nancy Schlichting, Commission on Care chairperson told the House committee. “Certainly, some elements of such a high-performing system are already in place. VA has high-quality clinical staff, and this integrated health care system is marked by good care-coordination. VHA today, however, relies significantly on community providers to augment the care it provides directly, although those community partners are not part of a cohesive system.”

According to Schlichting, fixing access issues “cannot be achieved by ‘tweaking’ existing programs or mounting a complex new delivery framework on a weak infrastructure platform.” Instead, the Commission recommended the creation of integrated systems approach to the VA that would re-engineer VA’s fundamental internal systems, both in terms of how it delivers health care as well as the technology it uses.

Veteran service organizations weighed in with cautious approval of many of the Commission’s recommendations, especially those that improved oversight, governance, and access to care, but cautioned against privatizing the VA.

“After two years of spirited and passionate debate about the future of veterans health care, we envision a clear path forward that builds on the strengths of the existing VA system, while expanding access by seamlessly integrating the best of community care to ensure no veteran must travel too far or wait too long for care,” Joy J. Ilem, national legislative director of Disabled American Veterans wrote in a letter submitted to the House committee. “Congress and VA must now begin the steps to finalize plans and move forward with the evolution of veterans health care.”

Despite the emerging consensus, a number of voices expressed concern about the impact of the Commission on Care’s proposals changes. A group of unions and professional organizations that represent VA employees (Association of VA Psychologist Leaders, Association of VA Social Workers, Nurses Organization of Veterans Affairs, Veterans Affairs Physician Assistant Association, American Federation of Government Employees, National Federation of Federal Employees, National Association of Government Employees, National Nurses United, the American Psychological Association, and National Association of Social Workers) expressed its concerns in a letter submitted to the House panel. “As organizations comprised of and representing health care practitioners, researchers, educators, administrators and personnel devoted to serving veterans, we have serious reservations about the report’s major recommendation to replace the current VHA with a new entity, to be known as the VHA Care System.” The letter argues that the proposed VHA Care System “disassembles one of the most effective, innovative features of current VHA care—the Primary Care/Mental Health Integration approach.”

In his Senate testimony, Secretary McDonald also expressed concern with the potential cost of some of the Commission on Care proposals. Currently the VA is spending  $13.5 billion in community care. According to McDonald, the VA would need $17 billion to make the upgrades it outlined in its October Plan to Consolidate Community Care, but he warned “the Commission on Care plan would be much more expensive than that.” More importantly, McDonald insisted, the VA should retain primary responsibility for the care of veterans. "We believe the VA needs to be the care coordinator," he insisted.

Another concern echoed by many of the commenters was the proposal to create an oversight board to provide governance, set long-term strategy, and direct and oversee reform. According to its critics, the proposal not only would undermine the authority of VA leadership, but could reduce congressional oversight as well. “NOVA strongly opposes giving an outside board—made up of civilian health care executives who may have never set foot into a VA facility—the authority to make decisions about the care and services provided America’s veterans,” argued Sharon Johnson, MSN, RN, president of the Nurses Organization of Veteran Affairs.

Mark Takata (D-Calif.) the ranking minority member of the House committee also expressed concern that the changes could impact VA clinicians’ access to high quality research, and clinician training. “The Commission on Care recommendations might in fact weaken the VA health care system,” Takata argued. “Proposals to funnels funding to private contractors and for profit care will take desperately needed resources away from our veterans and should be immediately rejected.... We cannot view expanded choice or the private sector as the panacea for solving the challenges the VA faces.”

Even with the clock ticking on the current election year, President Barak Obama and Congress appear ready to begin implementing at least some of the Commission on Care recommendations. In Senate and House of Representatives committee meetings over the past 2 weeks, a consensus has emerged to implement most of the Commission’s 18 recommendations. Still, most action is expected to take place after the November election, which will change who is in the White House and also could affect leadership within the VA as well as the House and Senate veteran oversight committees.

Currently 22% of veteran appointments are in community settings and the VA has already seen 5 million appointments through the Veterans Choice Program. Still, as VA Secretary Robert A. McDonald told the Senate committee on Wednesday, just 5,000 veterans are using community care only, which McDonald argued was evidence of veterans' strong desire to continue receiving VA care. The Veterans Choice Program is currently scheduled to expire August 7, 2017.  

“I strongly support the Commission's principle that creating a high-performing, integrated health care system that encompasses both VA and private care is critical to serving the needs of veterans,” President Obama said in a letter to the House Committee on Veterans Affairs. “It is critical that we preserve and continue to improve the VA health care system and ensure that VA has the ability to serve veterans.” The President also emphasized the importance of preserving the high quality of VA care, noting, “VA also provides unique, highly specialized care for many medical conditions, such as spinal cord and traumatic brain injuries, which are simply not available to the same extent outside of VA.”

“In our view that VHA must change, and change profoundly, because veterans deserve a better organized, high-performing health care system,” Nancy Schlichting, Commission on Care chairperson told the House committee. “Certainly, some elements of such a high-performing system are already in place. VA has high-quality clinical staff, and this integrated health care system is marked by good care-coordination. VHA today, however, relies significantly on community providers to augment the care it provides directly, although those community partners are not part of a cohesive system.”

According to Schlichting, fixing access issues “cannot be achieved by ‘tweaking’ existing programs or mounting a complex new delivery framework on a weak infrastructure platform.” Instead, the Commission recommended the creation of integrated systems approach to the VA that would re-engineer VA’s fundamental internal systems, both in terms of how it delivers health care as well as the technology it uses.

Veteran service organizations weighed in with cautious approval of many of the Commission’s recommendations, especially those that improved oversight, governance, and access to care, but cautioned against privatizing the VA.

“After two years of spirited and passionate debate about the future of veterans health care, we envision a clear path forward that builds on the strengths of the existing VA system, while expanding access by seamlessly integrating the best of community care to ensure no veteran must travel too far or wait too long for care,” Joy J. Ilem, national legislative director of Disabled American Veterans wrote in a letter submitted to the House committee. “Congress and VA must now begin the steps to finalize plans and move forward with the evolution of veterans health care.”

Despite the emerging consensus, a number of voices expressed concern about the impact of the Commission on Care’s proposals changes. A group of unions and professional organizations that represent VA employees (Association of VA Psychologist Leaders, Association of VA Social Workers, Nurses Organization of Veterans Affairs, Veterans Affairs Physician Assistant Association, American Federation of Government Employees, National Federation of Federal Employees, National Association of Government Employees, National Nurses United, the American Psychological Association, and National Association of Social Workers) expressed its concerns in a letter submitted to the House panel. “As organizations comprised of and representing health care practitioners, researchers, educators, administrators and personnel devoted to serving veterans, we have serious reservations about the report’s major recommendation to replace the current VHA with a new entity, to be known as the VHA Care System.” The letter argues that the proposed VHA Care System “disassembles one of the most effective, innovative features of current VHA care—the Primary Care/Mental Health Integration approach.”

In his Senate testimony, Secretary McDonald also expressed concern with the potential cost of some of the Commission on Care proposals. Currently the VA is spending  $13.5 billion in community care. According to McDonald, the VA would need $17 billion to make the upgrades it outlined in its October Plan to Consolidate Community Care, but he warned “the Commission on Care plan would be much more expensive than that.” More importantly, McDonald insisted, the VA should retain primary responsibility for the care of veterans. "We believe the VA needs to be the care coordinator," he insisted.

Another concern echoed by many of the commenters was the proposal to create an oversight board to provide governance, set long-term strategy, and direct and oversee reform. According to its critics, the proposal not only would undermine the authority of VA leadership, but could reduce congressional oversight as well. “NOVA strongly opposes giving an outside board—made up of civilian health care executives who may have never set foot into a VA facility—the authority to make decisions about the care and services provided America’s veterans,” argued Sharon Johnson, MSN, RN, president of the Nurses Organization of Veteran Affairs.

Mark Takata (D-Calif.) the ranking minority member of the House committee also expressed concern that the changes could impact VA clinicians’ access to high quality research, and clinician training. “The Commission on Care recommendations might in fact weaken the VA health care system,” Takata argued. “Proposals to funnels funding to private contractors and for profit care will take desperately needed resources away from our veterans and should be immediately rejected.... We cannot view expanded choice or the private sector as the panacea for solving the challenges the VA faces.”

LONDON—Evaluation of cortical lesions improves specificity of the diagnostic criteria for multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Assessment of cortical lesions, in concert with current McDonald criteria, also preserved a high level of diagnostic sensitivity and accuracy in a multicentric cohort of patients with clinically isolated syndrome, reported Paolo Preziosa, MD, Neuroimaging Research Unit at the Institute of Experimental Neurology and Division of Neuroscience at San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and his research colleagues.

Since the publication of the 2010 revised McDonald criteria, new data regarding the application of MRI for the diagnosis of MS have become available. In a single-center study, adding the assessment of cortical lesions has been shown to modify the diagnostic algorithm resulting in higher specificity.

In the present study, Dr. Preziosa and colleagues sought to test the performance of different sets of imaging criteria, including the assessment of cortical lesions, for the development of MS in a multicentric cohort of patients with clinically isolated syndrome.

The researchers analyzed brain double inversion recovery and brain and cord T2-weighted and post-contrast T1-weighted sequences acquired from 72 patients with clinically isolated syndrome from five European centers (Barcelona, Belgrade, Mainz, Milan, and Verona) within three months and after 12 months from disease onset. Patients were followed clinically for 24 or more months or until the development of clinically defined MS. Median follow-up was 24.2 months. Sensitivity, specificity, and accuracy of the different dissemination in space MRI criteria for the development of MS were tested.

At follow-up, 65 patients (90%) had clinically and/or radiologically definite MS. The sensitivity of all criteria was high (McDonald 2005, 83%; McDonald 2010, 92%; Filippi 2010, 80%). Specificity of Filippi 2010 was higher (67%) compared with the others (50% for McDonald 2005 and 2010). The accuracy of all criteria was high (McDonald 2005, 81%; McDonald 2010, 89%; Filippi 2010, 79%).

“The detection of cortical lesions in vivo using MRI should be considered in future clinical trials,” Dr. Preziosa said.

—Glenn S. Williams

LONDON—Evaluation of cortical lesions improves specificity of the diagnostic criteria for multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Assessment of cortical lesions, in concert with current McDonald criteria, also preserved a high level of diagnostic sensitivity and accuracy in a multicentric cohort of patients with clinically isolated syndrome, reported Paolo Preziosa, MD, Neuroimaging Research Unit at the Institute of Experimental Neurology and Division of Neuroscience at San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and his research colleagues.

Since the publication of the 2010 revised McDonald criteria, new data regarding the application of MRI for the diagnosis of MS have become available. In a single-center study, adding the assessment of cortical lesions has been shown to modify the diagnostic algorithm resulting in higher specificity.

In the present study, Dr. Preziosa and colleagues sought to test the performance of different sets of imaging criteria, including the assessment of cortical lesions, for the development of MS in a multicentric cohort of patients with clinically isolated syndrome.

The researchers analyzed brain double inversion recovery and brain and cord T2-weighted and post-contrast T1-weighted sequences acquired from 72 patients with clinically isolated syndrome from five European centers (Barcelona, Belgrade, Mainz, Milan, and Verona) within three months and after 12 months from disease onset. Patients were followed clinically for 24 or more months or until the development of clinically defined MS. Median follow-up was 24.2 months. Sensitivity, specificity, and accuracy of the different dissemination in space MRI criteria for the development of MS were tested.

At follow-up, 65 patients (90%) had clinically and/or radiologically definite MS. The sensitivity of all criteria was high (McDonald 2005, 83%; McDonald 2010, 92%; Filippi 2010, 80%). Specificity of Filippi 2010 was higher (67%) compared with the others (50% for McDonald 2005 and 2010). The accuracy of all criteria was high (McDonald 2005, 81%; McDonald 2010, 89%; Filippi 2010, 79%).

“The detection of cortical lesions in vivo using MRI should be considered in future clinical trials,” Dr. Preziosa said.

—Glenn S. Williams

LONDON—Evaluation of cortical lesions improves specificity of the diagnostic criteria for multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Assessment of cortical lesions, in concert with current McDonald criteria, also preserved a high level of diagnostic sensitivity and accuracy in a multicentric cohort of patients with clinically isolated syndrome, reported Paolo Preziosa, MD, Neuroimaging Research Unit at the Institute of Experimental Neurology and Division of Neuroscience at San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and his research colleagues.

Since the publication of the 2010 revised McDonald criteria, new data regarding the application of MRI for the diagnosis of MS have become available. In a single-center study, adding the assessment of cortical lesions has been shown to modify the diagnostic algorithm resulting in higher specificity.

In the present study, Dr. Preziosa and colleagues sought to test the performance of different sets of imaging criteria, including the assessment of cortical lesions, for the development of MS in a multicentric cohort of patients with clinically isolated syndrome.

The researchers analyzed brain double inversion recovery and brain and cord T2-weighted and post-contrast T1-weighted sequences acquired from 72 patients with clinically isolated syndrome from five European centers (Barcelona, Belgrade, Mainz, Milan, and Verona) within three months and after 12 months from disease onset. Patients were followed clinically for 24 or more months or until the development of clinically defined MS. Median follow-up was 24.2 months. Sensitivity, specificity, and accuracy of the different dissemination in space MRI criteria for the development of MS were tested.

At follow-up, 65 patients (90%) had clinically and/or radiologically definite MS. The sensitivity of all criteria was high (McDonald 2005, 83%; McDonald 2010, 92%; Filippi 2010, 80%). Specificity of Filippi 2010 was higher (67%) compared with the others (50% for McDonald 2005 and 2010). The accuracy of all criteria was high (McDonald 2005, 81%; McDonald 2010, 89%; Filippi 2010, 79%).

“The detection of cortical lesions in vivo using MRI should be considered in future clinical trials,” Dr. Preziosa said.

—Glenn S. Williams

November 11-13, 2016
Hotel Taj Palace
New Delhi, India

Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar

Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.

Preliminary Program

More Information/Register

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November 11-13, 2016
Hotel Taj Palace
New Delhi, India

Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar

Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.

Preliminary Program

More Information/Register

Share:

November 11-13, 2016
Hotel Taj Palace
New Delhi, India

Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar

Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.

Preliminary Program

More Information/Register

Share:

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“Our next goal is to determine how environmental factors such as diet can modulate MS pathogenesis through alterations of gut microbiota composition and intestinal immunity,” said Dr. Dalla Costa.

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“Our next goal is to determine how environmental factors such as diet can modulate MS pathogenesis through alterations of gut microbiota composition and intestinal immunity,” said Dr. Dalla Costa.

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“Our next goal is to determine how environmental factors such as diet can modulate MS pathogenesis through alterations of gut microbiota composition and intestinal immunity,” said Dr. Dalla Costa.

On May 31, 2016, the Food and Drug Administration approved Juvéderm Volbella XC for use in the lips for lip augmentation and for correction of perioral rhytids, in adults over the age of 21. In the U.S. pivotal clinical trial of 168 patients, Juvederm Volbella XC was found to increase lip fullness and soften the appearance of perioral rhytids in two-thirds through 1 year.

Like its previously approved predecessor Juvéderm Voluma XC, approved for the mid-face/cheek area, Juvéderm Volbella XC is composed of hyaluronic acid (HA) using Vycross technology. Vycross technology blends different molecular weights of hyaluronic acid together, allowing for longer duration of the product. Unlike Juvéderm Voluma XC (20 mg/mL), Juvéderm Volbella XC is a lower-concentration HA (15 mg/mL) and has a lower G prime and cohesivity, allowing more horizontal spread as opposed to a lift, which makes it more appropriate for injection into the lips and superficial perioral lines.¹

Juvéderm Volbella XC will not be available for use in the United States until October 2016. However, the product was first approved in Europe in 2011, and subsequently in Latin America, the Middle East, Asia Pacific, and Canada. What has been the experience of our neighboring colleagues?

In a randomized, prospective, 12-month controlled European study of 280 patients comparing Volbella to a nonanimal stabilized hyaluronic acid (NASHA), Volbella was found to be noninferior to NASHA at 3 months.² Improvements in lip fullness, perioral lines, and oral commissures for Volbella were statistically significant at 6 and 12 months. Acute swelling was also noted to be less.

In a German 62-patient study with primary endpoints of satisfaction with improvement and look and feel of the lips, a high degree of subject satisfaction with aesthetic improvement in the lips, as well as with their natural look and feel, was noted among 83.6% and 75%-93%, respectively.³

In a retrospective chart review of 400 patients in Israel, where Volbella was injected into tear troughs (disclaimer: not approved for tear troughs in the United States) and/or lips, 17 patients (4.25%) developed prolonged inflammatory cutaneous reactions, lasting up to 11 months, which recurred (with an average number of 3.17 episodes) and occurred late (with an average onset of 8.41 weeks after the injection).⁴ The reactions were treated with antibiotics and hyaluronidase injections. The finding in this published report is higher than the 0.02% of delayed-onset inflammatory reaction previously reported with HA fillers.

With a full armamentarium of HA and non-HA fillers on the market, we are lucky to have many options to select from to treat aesthetic concerns of patients. For lip and perioral enhancement in the United States, Restylane, Juvéderm, Belotero, and now Volbella are all excellent options. As the dermal filler portfolio available internationally is larger than that in the United States, much can be learned from the experience of our international colleagues.

References

1. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):139S-48S.

2. J Drugs Dermatol. 2015 Dec;14(12):1444-52.

3. J Cosmet Dermatol. 2014 Jun;13(2):125-34.

4. Dermatol Surg. 2016 Jan;42(1):31-7.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. Dr. Wesley has no disclosures with regard to Volbella; she participated in clinical trials for Juvéderm Voluma. Dr. Talakoub is a national trainer for Juvéderm manufacturer Allergan for all its injectables.

On May 31, 2016, the Food and Drug Administration approved Juvéderm Volbella XC for use in the lips for lip augmentation and for correction of perioral rhytids, in adults over the age of 21. In the U.S. pivotal clinical trial of 168 patients, Juvederm Volbella XC was found to increase lip fullness and soften the appearance of perioral rhytids in two-thirds through 1 year.

Like its previously approved predecessor Juvéderm Voluma XC, approved for the mid-face/cheek area, Juvéderm Volbella XC is composed of hyaluronic acid (HA) using Vycross technology. Vycross technology blends different molecular weights of hyaluronic acid together, allowing for longer duration of the product. Unlike Juvéderm Voluma XC (20 mg/mL), Juvéderm Volbella XC is a lower-concentration HA (15 mg/mL) and has a lower G prime and cohesivity, allowing more horizontal spread as opposed to a lift, which makes it more appropriate for injection into the lips and superficial perioral lines.¹

Juvéderm Volbella XC will not be available for use in the United States until October 2016. However, the product was first approved in Europe in 2011, and subsequently in Latin America, the Middle East, Asia Pacific, and Canada. What has been the experience of our neighboring colleagues?

In a randomized, prospective, 12-month controlled European study of 280 patients comparing Volbella to a nonanimal stabilized hyaluronic acid (NASHA), Volbella was found to be noninferior to NASHA at 3 months.² Improvements in lip fullness, perioral lines, and oral commissures for Volbella were statistically significant at 6 and 12 months. Acute swelling was also noted to be less.

In a German 62-patient study with primary endpoints of satisfaction with improvement and look and feel of the lips, a high degree of subject satisfaction with aesthetic improvement in the lips, as well as with their natural look and feel, was noted among 83.6% and 75%-93%, respectively.³

In a retrospective chart review of 400 patients in Israel, where Volbella was injected into tear troughs (disclaimer: not approved for tear troughs in the United States) and/or lips, 17 patients (4.25%) developed prolonged inflammatory cutaneous reactions, lasting up to 11 months, which recurred (with an average number of 3.17 episodes) and occurred late (with an average onset of 8.41 weeks after the injection).⁴ The reactions were treated with antibiotics and hyaluronidase injections. The finding in this published report is higher than the 0.02% of delayed-onset inflammatory reaction previously reported with HA fillers.

With a full armamentarium of HA and non-HA fillers on the market, we are lucky to have many options to select from to treat aesthetic concerns of patients. For lip and perioral enhancement in the United States, Restylane, Juvéderm, Belotero, and now Volbella are all excellent options. As the dermal filler portfolio available internationally is larger than that in the United States, much can be learned from the experience of our international colleagues.

References

1. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):139S-48S.

2. J Drugs Dermatol. 2015 Dec;14(12):1444-52.

3. J Cosmet Dermatol. 2014 Jun;13(2):125-34.

4. Dermatol Surg. 2016 Jan;42(1):31-7.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. Dr. Wesley has no disclosures with regard to Volbella; she participated in clinical trials for Juvéderm Voluma. Dr. Talakoub is a national trainer for Juvéderm manufacturer Allergan for all its injectables.

On May 31, 2016, the Food and Drug Administration approved Juvéderm Volbella XC for use in the lips for lip augmentation and for correction of perioral rhytids, in adults over the age of 21. In the U.S. pivotal clinical trial of 168 patients, Juvederm Volbella XC was found to increase lip fullness and soften the appearance of perioral rhytids in two-thirds through 1 year.

Like its previously approved predecessor Juvéderm Voluma XC, approved for the mid-face/cheek area, Juvéderm Volbella XC is composed of hyaluronic acid (HA) using Vycross technology. Vycross technology blends different molecular weights of hyaluronic acid together, allowing for longer duration of the product. Unlike Juvéderm Voluma XC (20 mg/mL), Juvéderm Volbella XC is a lower-concentration HA (15 mg/mL) and has a lower G prime and cohesivity, allowing more horizontal spread as opposed to a lift, which makes it more appropriate for injection into the lips and superficial perioral lines.¹

Juvéderm Volbella XC will not be available for use in the United States until October 2016. However, the product was first approved in Europe in 2011, and subsequently in Latin America, the Middle East, Asia Pacific, and Canada. What has been the experience of our neighboring colleagues?

In a randomized, prospective, 12-month controlled European study of 280 patients comparing Volbella to a nonanimal stabilized hyaluronic acid (NASHA), Volbella was found to be noninferior to NASHA at 3 months.² Improvements in lip fullness, perioral lines, and oral commissures for Volbella were statistically significant at 6 and 12 months. Acute swelling was also noted to be less.

In a German 62-patient study with primary endpoints of satisfaction with improvement and look and feel of the lips, a high degree of subject satisfaction with aesthetic improvement in the lips, as well as with their natural look and feel, was noted among 83.6% and 75%-93%, respectively.³

In a retrospective chart review of 400 patients in Israel, where Volbella was injected into tear troughs (disclaimer: not approved for tear troughs in the United States) and/or lips, 17 patients (4.25%) developed prolonged inflammatory cutaneous reactions, lasting up to 11 months, which recurred (with an average number of 3.17 episodes) and occurred late (with an average onset of 8.41 weeks after the injection).⁴ The reactions were treated with antibiotics and hyaluronidase injections. The finding in this published report is higher than the 0.02% of delayed-onset inflammatory reaction previously reported with HA fillers.

With a full armamentarium of HA and non-HA fillers on the market, we are lucky to have many options to select from to treat aesthetic concerns of patients. For lip and perioral enhancement in the United States, Restylane, Juvéderm, Belotero, and now Volbella are all excellent options. As the dermal filler portfolio available internationally is larger than that in the United States, much can be learned from the experience of our international colleagues.

References

1. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):139S-48S.

2. J Drugs Dermatol. 2015 Dec;14(12):1444-52.

3. J Cosmet Dermatol. 2014 Jun;13(2):125-34.

4. Dermatol Surg. 2016 Jan;42(1):31-7.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. Dr. Wesley has no disclosures with regard to Volbella; she participated in clinical trials for Juvéderm Voluma. Dr. Talakoub is a national trainer for Juvéderm manufacturer Allergan for all its injectables.

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.

©Zerbor/Thinkstock

A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.

Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.

Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.

A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.

Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.

Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.

A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.

Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.

A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.

From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.

Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.

Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.

The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.

An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.

A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.

A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.

©Zerbor/Thinkstock

A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.

Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.

Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.

A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.

Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.

Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.

A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.

Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.

A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.

From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.

Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.

Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.

The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.

An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.

A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.

A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.

©Zerbor/Thinkstock

A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.

Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.

Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.

A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.

Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.

Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.

A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.

Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.

A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.

From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.

Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.

Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.

The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.

An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.

A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.

A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.

[email protected]

On Twitter @richpizzi

Suicide continues to be a major public health problem in the United States. It is the second leading cause of death in young people aged 10-24 years, according to 2010 injury data from the Centers from Disease Control and Prevention.¹ This problem disproportionately affects lesbian, gay, bisexual, and transgender (LGBT) youth. Compared to their heterosexual peers, LGBT youth are four times as likely to attempt suicide.² In addition, almost 50% of transgender youth have attempted suicide.³

Why are LGBT youth at high risk for suicide? Antigay and antitrans stigma and discrimination against LGBT youth create a very stressful environment. For example, LGBT youth are two times more likely than are heterosexual youth to experience bullying⁴ because of their sexual orientation, and half of transgender youth have reported bullying because of their gender identity.³ LGBT youth tend to perceive lower levels of parental support than do heterosexual youth.^5-8 A combination of harassment from peers and decreased perceived support from families increases the risk for suicide in LGBT youth.

However, there are factors that can reduce this risk. LGBT youth whose parents reject their sexual orientation or gender identity are eight times as likely to be suicidal,^3,9 while in contrast, LGBT youth whose parents are more accepting are less likely to be suicidal.¹⁰ These studies underscore the importance of social support in reducing the stress from antigay and antitrans discrimination, and therefore, play a role in preventing suicide.

Health care providers are another source of support for LGBT youth. They can play a role in providing education and preventing suicide in this population because many victims of suicide have visited a health care provider before attempting to kill themselves.¹¹ It is important for providers to screen for suicide in their patients. Although there is no lab test for suicidal ideation, suicidal adolescents tend to have certain risk factors. In addition to being LGBT, being bullied, and having a lack of social support, other risk factors are psychiatric illness, a history of being impulsive, alcohol and substance abuse, and most important of all, a previous suicide attempt.¹²

©ArishaRay/ThinkStock

When screening for suicide risk, always remember that at the beginning of any visit with an adolescent, remind them about confidentiality and its limits (e.g., breaking confidentiality if the patient is suicidal). Although this appears counterintuitive, it actually builds rapport between you and the patient. If you don’t discuss the limits of confidentiality beforehand and have to break it because the patient is suicidal, the patient is less likely to tell you again in the future. Once you suspect suicidal ideation based on the above risk factors, you can ask:

•  Have you thought about ending your own life or would you rather be dead?

•  Have you done something to harm yourself or to end your life?

•  Have you considered ways to end your own life?¹²

Some clinicians have expressed concern over asking about suicide in their adolescent patients, but doing so does not induce suicidal thoughts.¹³ If a patient does express any of the above, the clinician must then inquire about other risk factors that increase the individual’s chances of completing suicide. The American Association of Suicidology has listed several warning signs of imminent suicide, which can be remembered with the acronym IS PATH WARM. This stands for Ideation, Substance use, Purposelessness, heightened Anxiety, feeling Trapped, feeling Hopeless, Withdrawal from friends and family, uncontrollable Anger, engaging in Reckless behavior, and dramatic Mood changes.¹⁴

If a patient threatens to kill him/herself, has a specific plan to do so, or speaks about death and suicide, then the clinician must act immediately. Although sending a patient to the emergency department is the safest option, it is not the only option. If a good support system is present, and the patient lives in an environment where he or she does not have the means to carry out a suicide (e.g., there are no guns in the home), then the clinician can create a safety plan for the patient. A safety plan is different from a “no suicide contract.” A no suicide contract is a written commitment that the patient does not engage in suicidal behavior. Many experts caution against a no suicide contract because it can create a false sense of security for the clinician and does not address the strategies needed to combat feelings of suicidality.^15,16

Usually with a safety plan, the clinician and the patient identify several people the patient can contact if the patient feels suicidal. In addition, the clinician and the patient can discuss ways the patient can cope with his/her feelings or distract himself/herself from suicidal thoughts (e.g., going out for a walk, watching a movie, etc.). Finally, if these methods fail, patients are provided with emergency hotlines or directed to the emergency department. The Suicide Prevention Resource Center has a template of a patient safety plan.

Finally, clinicians should be proactive in preventing suicide, especially for LGBT youth. Because bullying is a risk factor for suicide, and because LGBT youth are disproportionately affected by bullying, clinicians should advocate for antibullying school policies and advocate for schools to be more LGBT friendly. Clinicians also should speak to the community about suicide, its warning signs, and how to address it. Just like with any disease, prevention is the most effective form of treatment.

As clinicians, we should always be on the lookout for suicide in our young patients, especially LGBT youth. For many LGBT youth, we may be the only source of support. If patients are suicidal, we should work with them to determine how to keep the them safe. We have a powerful voice in the community. We can advocate for making schools safe for LGBT youth and educate the community in suicide prevention. Such a powerful voice proclaiming that it gets better can save a life.

Resources

• The Trevor Project: A non-profit organization dedicated to prevent suicide in LGBT Youth (www.thetrevorproject.org)

• It Gets Better Project: Another website dedicated to preventing suicide in LGBT youth by promoting the message that life will improve for LGBT teens (www.itgetsbetter.org)

• Patient Safety Plan Template from the Suicide Prevention Resource Center (www.sprc.org)

References

1. CDC. NCIPC. Web-based Injury Statistics Query and Reporting System (WISQARS). 2010.

2. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

3. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. (Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

4. J Adolesc Health. 2014 Sep;55(3):432-8.

5. J Youth Adolesc. 2013 Mar;42(3):376-93.

6. J Youth Adolesc. 2010 Oct;39(10):1189-98.

7. School Psychology Review. 2008;37(2):202-16.

8. J Homosex. 2010;57(2):287-309.

9. Pediatrics. 2009 Jan;123(1):346-52.

10. J Child Adolesc Psychiatr Nurs. 2010 Nov;23(4):205-13.

11. Mayo Clin Proc. 2011 Aug;86(8):792-800.

12. Ital J Pediatr. 2015 Jul 7;41:49.

13. Ment Health Fam Med. 2008 Dec;5(4):229-35.

14. Know the Warning Signs of Suicide. American Association of Suicidology.

15. J Psychiatr Ment Health Nurs. 2008 Aug;15(6):512-22.

16. J Amer Acad Psych Law. 1999;27(3):445-50.

Dr. Montano is a physician at Children’s Hospital of Pittsburgh of UPMC and a clinical instructor of pediatrics at the University of Pittsburgh School of Medicine.

Suicide continues to be a major public health problem in the United States. It is the second leading cause of death in young people aged 10-24 years, according to 2010 injury data from the Centers from Disease Control and Prevention.¹ This problem disproportionately affects lesbian, gay, bisexual, and transgender (LGBT) youth. Compared to their heterosexual peers, LGBT youth are four times as likely to attempt suicide.² In addition, almost 50% of transgender youth have attempted suicide.³

Why are LGBT youth at high risk for suicide? Antigay and antitrans stigma and discrimination against LGBT youth create a very stressful environment. For example, LGBT youth are two times more likely than are heterosexual youth to experience bullying⁴ because of their sexual orientation, and half of transgender youth have reported bullying because of their gender identity.³ LGBT youth tend to perceive lower levels of parental support than do heterosexual youth.^5-8 A combination of harassment from peers and decreased perceived support from families increases the risk for suicide in LGBT youth.

However, there are factors that can reduce this risk. LGBT youth whose parents reject their sexual orientation or gender identity are eight times as likely to be suicidal,^3,9 while in contrast, LGBT youth whose parents are more accepting are less likely to be suicidal.¹⁰ These studies underscore the importance of social support in reducing the stress from antigay and antitrans discrimination, and therefore, play a role in preventing suicide.

Health care providers are another source of support for LGBT youth. They can play a role in providing education and preventing suicide in this population because many victims of suicide have visited a health care provider before attempting to kill themselves.¹¹ It is important for providers to screen for suicide in their patients. Although there is no lab test for suicidal ideation, suicidal adolescents tend to have certain risk factors. In addition to being LGBT, being bullied, and having a lack of social support, other risk factors are psychiatric illness, a history of being impulsive, alcohol and substance abuse, and most important of all, a previous suicide attempt.¹²

©ArishaRay/ThinkStock

When screening for suicide risk, always remember that at the beginning of any visit with an adolescent, remind them about confidentiality and its limits (e.g., breaking confidentiality if the patient is suicidal). Although this appears counterintuitive, it actually builds rapport between you and the patient. If you don’t discuss the limits of confidentiality beforehand and have to break it because the patient is suicidal, the patient is less likely to tell you again in the future. Once you suspect suicidal ideation based on the above risk factors, you can ask:

•  Have you thought about ending your own life or would you rather be dead?

•  Have you done something to harm yourself or to end your life?

•  Have you considered ways to end your own life?¹²

Some clinicians have expressed concern over asking about suicide in their adolescent patients, but doing so does not induce suicidal thoughts.¹³ If a patient does express any of the above, the clinician must then inquire about other risk factors that increase the individual’s chances of completing suicide. The American Association of Suicidology has listed several warning signs of imminent suicide, which can be remembered with the acronym IS PATH WARM. This stands for Ideation, Substance use, Purposelessness, heightened Anxiety, feeling Trapped, feeling Hopeless, Withdrawal from friends and family, uncontrollable Anger, engaging in Reckless behavior, and dramatic Mood changes.¹⁴

If a patient threatens to kill him/herself, has a specific plan to do so, or speaks about death and suicide, then the clinician must act immediately. Although sending a patient to the emergency department is the safest option, it is not the only option. If a good support system is present, and the patient lives in an environment where he or she does not have the means to carry out a suicide (e.g., there are no guns in the home), then the clinician can create a safety plan for the patient. A safety plan is different from a “no suicide contract.” A no suicide contract is a written commitment that the patient does not engage in suicidal behavior. Many experts caution against a no suicide contract because it can create a false sense of security for the clinician and does not address the strategies needed to combat feelings of suicidality.^15,16

Usually with a safety plan, the clinician and the patient identify several people the patient can contact if the patient feels suicidal. In addition, the clinician and the patient can discuss ways the patient can cope with his/her feelings or distract himself/herself from suicidal thoughts (e.g., going out for a walk, watching a movie, etc.). Finally, if these methods fail, patients are provided with emergency hotlines or directed to the emergency department. The Suicide Prevention Resource Center has a template of a patient safety plan.

Finally, clinicians should be proactive in preventing suicide, especially for LGBT youth. Because bullying is a risk factor for suicide, and because LGBT youth are disproportionately affected by bullying, clinicians should advocate for antibullying school policies and advocate for schools to be more LGBT friendly. Clinicians also should speak to the community about suicide, its warning signs, and how to address it. Just like with any disease, prevention is the most effective form of treatment.

As clinicians, we should always be on the lookout for suicide in our young patients, especially LGBT youth. For many LGBT youth, we may be the only source of support. If patients are suicidal, we should work with them to determine how to keep the them safe. We have a powerful voice in the community. We can advocate for making schools safe for LGBT youth and educate the community in suicide prevention. Such a powerful voice proclaiming that it gets better can save a life.

Resources

• The Trevor Project: A non-profit organization dedicated to prevent suicide in LGBT Youth (www.thetrevorproject.org)

• It Gets Better Project: Another website dedicated to preventing suicide in LGBT youth by promoting the message that life will improve for LGBT teens (www.itgetsbetter.org)

• Patient Safety Plan Template from the Suicide Prevention Resource Center (www.sprc.org)

References

1. CDC. NCIPC. Web-based Injury Statistics Query and Reporting System (WISQARS). 2010.

2. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

3. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. (Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

4. J Adolesc Health. 2014 Sep;55(3):432-8.

5. J Youth Adolesc. 2013 Mar;42(3):376-93.

6. J Youth Adolesc. 2010 Oct;39(10):1189-98.

7. School Psychology Review. 2008;37(2):202-16.

8. J Homosex. 2010;57(2):287-309.

9. Pediatrics. 2009 Jan;123(1):346-52.

10. J Child Adolesc Psychiatr Nurs. 2010 Nov;23(4):205-13.

11. Mayo Clin Proc. 2011 Aug;86(8):792-800.

12. Ital J Pediatr. 2015 Jul 7;41:49.

13. Ment Health Fam Med. 2008 Dec;5(4):229-35.

14. Know the Warning Signs of Suicide. American Association of Suicidology.

15. J Psychiatr Ment Health Nurs. 2008 Aug;15(6):512-22.

16. J Amer Acad Psych Law. 1999;27(3):445-50.

Dr. Montano is a physician at Children’s Hospital of Pittsburgh of UPMC and a clinical instructor of pediatrics at the University of Pittsburgh School of Medicine.

Suicide continues to be a major public health problem in the United States. It is the second leading cause of death in young people aged 10-24 years, according to 2010 injury data from the Centers from Disease Control and Prevention.¹ This problem disproportionately affects lesbian, gay, bisexual, and transgender (LGBT) youth. Compared to their heterosexual peers, LGBT youth are four times as likely to attempt suicide.² In addition, almost 50% of transgender youth have attempted suicide.³

Why are LGBT youth at high risk for suicide? Antigay and antitrans stigma and discrimination against LGBT youth create a very stressful environment. For example, LGBT youth are two times more likely than are heterosexual youth to experience bullying⁴ because of their sexual orientation, and half of transgender youth have reported bullying because of their gender identity.³ LGBT youth tend to perceive lower levels of parental support than do heterosexual youth.^5-8 A combination of harassment from peers and decreased perceived support from families increases the risk for suicide in LGBT youth.

However, there are factors that can reduce this risk. LGBT youth whose parents reject their sexual orientation or gender identity are eight times as likely to be suicidal,^3,9 while in contrast, LGBT youth whose parents are more accepting are less likely to be suicidal.¹⁰ These studies underscore the importance of social support in reducing the stress from antigay and antitrans discrimination, and therefore, play a role in preventing suicide.

Health care providers are another source of support for LGBT youth. They can play a role in providing education and preventing suicide in this population because many victims of suicide have visited a health care provider before attempting to kill themselves.¹¹ It is important for providers to screen for suicide in their patients. Although there is no lab test for suicidal ideation, suicidal adolescents tend to have certain risk factors. In addition to being LGBT, being bullied, and having a lack of social support, other risk factors are psychiatric illness, a history of being impulsive, alcohol and substance abuse, and most important of all, a previous suicide attempt.¹²

©ArishaRay/ThinkStock

When screening for suicide risk, always remember that at the beginning of any visit with an adolescent, remind them about confidentiality and its limits (e.g., breaking confidentiality if the patient is suicidal). Although this appears counterintuitive, it actually builds rapport between you and the patient. If you don’t discuss the limits of confidentiality beforehand and have to break it because the patient is suicidal, the patient is less likely to tell you again in the future. Once you suspect suicidal ideation based on the above risk factors, you can ask:

•  Have you thought about ending your own life or would you rather be dead?

•  Have you done something to harm yourself or to end your life?

•  Have you considered ways to end your own life?¹²

Some clinicians have expressed concern over asking about suicide in their adolescent patients, but doing so does not induce suicidal thoughts.¹³ If a patient does express any of the above, the clinician must then inquire about other risk factors that increase the individual’s chances of completing suicide. The American Association of Suicidology has listed several warning signs of imminent suicide, which can be remembered with the acronym IS PATH WARM. This stands for Ideation, Substance use, Purposelessness, heightened Anxiety, feeling Trapped, feeling Hopeless, Withdrawal from friends and family, uncontrollable Anger, engaging in Reckless behavior, and dramatic Mood changes.¹⁴

If a patient threatens to kill him/herself, has a specific plan to do so, or speaks about death and suicide, then the clinician must act immediately. Although sending a patient to the emergency department is the safest option, it is not the only option. If a good support system is present, and the patient lives in an environment where he or she does not have the means to carry out a suicide (e.g., there are no guns in the home), then the clinician can create a safety plan for the patient. A safety plan is different from a “no suicide contract.” A no suicide contract is a written commitment that the patient does not engage in suicidal behavior. Many experts caution against a no suicide contract because it can create a false sense of security for the clinician and does not address the strategies needed to combat feelings of suicidality.^15,16

Usually with a safety plan, the clinician and the patient identify several people the patient can contact if the patient feels suicidal. In addition, the clinician and the patient can discuss ways the patient can cope with his/her feelings or distract himself/herself from suicidal thoughts (e.g., going out for a walk, watching a movie, etc.). Finally, if these methods fail, patients are provided with emergency hotlines or directed to the emergency department. The Suicide Prevention Resource Center has a template of a patient safety plan.

Finally, clinicians should be proactive in preventing suicide, especially for LGBT youth. Because bullying is a risk factor for suicide, and because LGBT youth are disproportionately affected by bullying, clinicians should advocate for antibullying school policies and advocate for schools to be more LGBT friendly. Clinicians also should speak to the community about suicide, its warning signs, and how to address it. Just like with any disease, prevention is the most effective form of treatment.

As clinicians, we should always be on the lookout for suicide in our young patients, especially LGBT youth. For many LGBT youth, we may be the only source of support. If patients are suicidal, we should work with them to determine how to keep the them safe. We have a powerful voice in the community. We can advocate for making schools safe for LGBT youth and educate the community in suicide prevention. Such a powerful voice proclaiming that it gets better can save a life.

Resources

• The Trevor Project: A non-profit organization dedicated to prevent suicide in LGBT Youth (www.thetrevorproject.org)

• It Gets Better Project: Another website dedicated to preventing suicide in LGBT youth by promoting the message that life will improve for LGBT teens (www.itgetsbetter.org)

• Patient Safety Plan Template from the Suicide Prevention Resource Center (www.sprc.org)

References

1. CDC. NCIPC. Web-based Injury Statistics Query and Reporting System (WISQARS). 2010.

2. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

3. Injustice at Every Turn: A Report of the National Transgender Discrimination Survey. (Washington: National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

4. J Adolesc Health. 2014 Sep;55(3):432-8.

5. J Youth Adolesc. 2013 Mar;42(3):376-93.

6. J Youth Adolesc. 2010 Oct;39(10):1189-98.

7. School Psychology Review. 2008;37(2):202-16.

8. J Homosex. 2010;57(2):287-309.

9. Pediatrics. 2009 Jan;123(1):346-52.

10. J Child Adolesc Psychiatr Nurs. 2010 Nov;23(4):205-13.

11. Mayo Clin Proc. 2011 Aug;86(8):792-800.

12. Ital J Pediatr. 2015 Jul 7;41:49.

13. Ment Health Fam Med. 2008 Dec;5(4):229-35.

14. Know the Warning Signs of Suicide. American Association of Suicidology.

15. J Psychiatr Ment Health Nurs. 2008 Aug;15(6):512-22.

16. J Amer Acad Psych Law. 1999;27(3):445-50.

Dr. Montano is a physician at Children’s Hospital of Pittsburgh of UPMC and a clinical instructor of pediatrics at the University of Pittsburgh School of Medicine.

(This column is the second in a three-part series.)

Question: A penicillin-allergic patient died from massive hemolysis after receiving the antibiotic ceftriaxone (Rocephin). The plaintiff alleged that the defendant was grossly negligent in administering the drug and subsequently refusing to treat or to readmit the decedent.

If this case is referred to the state’s medical board, which of the following statements is best?

A. The outcome depends on the jurisdiction.

B. Substandard medical care is not part of professional misconduct, which is what a medical board is supposed to look at.

C. Disciplinary action requires a simple showing of ordinary negligence.

D. Disciplinary action requires more than one act of ordinary negligence.

E. Disciplinary action requires proof of gross negligence.

Answer: A. Under the Medical Practice Act, each state authorizes its medical board to issue licenses and regulate physician practice. Professional misconduct is about unprofessional behavior, and covers both ethical breach and substandard care.

Medical boards do not typically adjudicate single acts of ordinary negligence, leaving them instead to the tort system and civil lawsuits. However, grossly culpable misconduct – even in a single instance – or a recurring pattern of ordinary negligence can come under medical board review. And it is common practice for boards to use malpractice data as a tool to trigger further investigations, such as a certain number of malpractice settlements over a given span of time.

States vary somewhat over when to investigate a complaint of alleged substandard practice. In California, the term “unprofessional conduct” is codified under section 2234 of the California Business and Professions Code, and the errant doctor is subject to disciplinary sanction if there is gross negligence, repeated negligent acts (defined as two or more negligent acts or omissions), or incompetence.

In Hawaii, the disciplinary law is set up under Hawaii Revised Statutes section 453-8, which lists 15 situations of wrongdoing. In the malpractice category, Hawaii’s law uses the terms hazardous misconduct, hazardous negligence, incompetence, or multiple instances of negligence.

The state of New York defines professional misconduct by reference to a comprehensive list of 49 categories under section 6530, which include gross incompetence or gross negligence on a single occasion, or negligence or incompetence on more than one occasion.

However, Maryland is an example of a jurisdiction that does not require gross or repeated negligence; the state considers any failure to meet the appropriate medical standards as professional misconduct.¹

But what constitutes gross negligence?

The vast majority of medical malpractice lawsuits allege ordinary, not gross negligence. Ordinary negligence is a well-defined legal term, as illustrated in Prosser’s Textbook on Torts: “The formula under which this usually is put to the jury is that the doctor must have and use the knowledge, skill, and care ordinarily possessed and employed by members of the profession in good standing.”²

In contrast, there is no universal definition for the term gross negligence. Everyone recognizes it denotes a greater degree of culpability than ordinary negligence, but how much greater?

According to the California Supreme Court, gross negligence may be said to be “the want of even scant care or an extreme departure from the ordinary standard of conduct.”³ The law in Texas stipulates: “Gross negligence means more than momentary thoughtlessness, inadvertence, or error of judgment. It means an entire want of care as to establish that the act or omission was the result of actual, conscious indifference to the rights, safety, and welfare of the person affected.”⁴

Examples in case law of gross negligence (or where punitive damages were awarded, which usually signify egregious conduct) include a doctor’s wanton failure to provide follow-up care for a child who developed fever and gangrenous toes following foot surgery,⁵ the prescription of an excessive number of birth control pills (more than 1,000 pills within a time period when less than 200 were sufficient) with resulting liver complications,⁶ and leaving behind a 6.5-inch clamp in a surgical incision.⁷

On the other hand, a Connecticut court (which decided the case in the hypothetical above) ruled that, under the facts, the defendant’s conduct did not meet the high threshold of egregiousness that defines gross negligence.⁸

As in any malpractice lawsuit, a medical board investigation involves determining whether the accused physician has met the standard of care in his or her specialty, and boards usually look to expert community physicians to articulate that requisite standard.

Compared with a civil lawsuit, a disciplinary hearing has the physician at a disadvantage. Medical board complaints are easier to file; the complaining party does not need an attorney; impartial expert witnesses are the responsibility of the board, not the complainant; and no patient injury needs to be shown.

Furthermore, a settlement is rarely reached or negotiated, and penalties are potentially far more serious, such as public posting of an adverse decision and restriction or actual loss of licensure.

Reputational loss also is arguably more devastating with board censure, because an adverse action taken by a medical board indicates a violation of the Medical Practice Act. In contrast, malpractice settlements or verdicts are regularly viewed as unreliable measures of a physician’s competence.

Still, two features work in favor of the doctor facing a board hearing. First, the misconduct typically has to be recurrent or grossly negligent, rather than an isolated case of carelessness. And second, some boards (only a small minority) require evidentiary proof of fault to be “clear and convincing,” instead of the familiar “more probable than not” standard that is used in a civil negligence suit. This makes it theoretically harder to reach a finding of culpability against the doctor.

References

1. Md. Code Ann. Health Occ. section 14-404.

2. Prosser and Keeton on Torts, 5th ed., 1984.

3. Van Meter v. Bent Construction Co., 297 P.2d 644 (Cal. 1956).

4. Texas Civil Practice & Remedies Code section 41.001(7).

5. Dempsey v. Phelps, 700 So.2d 1340 (Ala. 1997).

6. Jackson v. Taylor, 912 F.2d 795 (5th Cir. 1990).

7. Fox v. Oklahoma Memorial Hospital, 774 P.2d 459 (Ok. 1989).

8. Boone v. William W. Backus Hospital, 864 A.2d 1 (Conn. 2005).

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].

(This column is the second in a three-part series.)

Question: A penicillin-allergic patient died from massive hemolysis after receiving the antibiotic ceftriaxone (Rocephin). The plaintiff alleged that the defendant was grossly negligent in administering the drug and subsequently refusing to treat or to readmit the decedent.

If this case is referred to the state’s medical board, which of the following statements is best?

A. The outcome depends on the jurisdiction.

B. Substandard medical care is not part of professional misconduct, which is what a medical board is supposed to look at.

C. Disciplinary action requires a simple showing of ordinary negligence.

D. Disciplinary action requires more than one act of ordinary negligence.

E. Disciplinary action requires proof of gross negligence.

Answer: A. Under the Medical Practice Act, each state authorizes its medical board to issue licenses and regulate physician practice. Professional misconduct is about unprofessional behavior, and covers both ethical breach and substandard care.

Medical boards do not typically adjudicate single acts of ordinary negligence, leaving them instead to the tort system and civil lawsuits. However, grossly culpable misconduct – even in a single instance – or a recurring pattern of ordinary negligence can come under medical board review. And it is common practice for boards to use malpractice data as a tool to trigger further investigations, such as a certain number of malpractice settlements over a given span of time.

States vary somewhat over when to investigate a complaint of alleged substandard practice. In California, the term “unprofessional conduct” is codified under section 2234 of the California Business and Professions Code, and the errant doctor is subject to disciplinary sanction if there is gross negligence, repeated negligent acts (defined as two or more negligent acts or omissions), or incompetence.

In Hawaii, the disciplinary law is set up under Hawaii Revised Statutes section 453-8, which lists 15 situations of wrongdoing. In the malpractice category, Hawaii’s law uses the terms hazardous misconduct, hazardous negligence, incompetence, or multiple instances of negligence.

The state of New York defines professional misconduct by reference to a comprehensive list of 49 categories under section 6530, which include gross incompetence or gross negligence on a single occasion, or negligence or incompetence on more than one occasion.

However, Maryland is an example of a jurisdiction that does not require gross or repeated negligence; the state considers any failure to meet the appropriate medical standards as professional misconduct.¹

But what constitutes gross negligence?

The vast majority of medical malpractice lawsuits allege ordinary, not gross negligence. Ordinary negligence is a well-defined legal term, as illustrated in Prosser’s Textbook on Torts: “The formula under which this usually is put to the jury is that the doctor must have and use the knowledge, skill, and care ordinarily possessed and employed by members of the profession in good standing.”²

In contrast, there is no universal definition for the term gross negligence. Everyone recognizes it denotes a greater degree of culpability than ordinary negligence, but how much greater?

According to the California Supreme Court, gross negligence may be said to be “the want of even scant care or an extreme departure from the ordinary standard of conduct.”³ The law in Texas stipulates: “Gross negligence means more than momentary thoughtlessness, inadvertence, or error of judgment. It means an entire want of care as to establish that the act or omission was the result of actual, conscious indifference to the rights, safety, and welfare of the person affected.”⁴

Examples in case law of gross negligence (or where punitive damages were awarded, which usually signify egregious conduct) include a doctor’s wanton failure to provide follow-up care for a child who developed fever and gangrenous toes following foot surgery,⁵ the prescription of an excessive number of birth control pills (more than 1,000 pills within a time period when less than 200 were sufficient) with resulting liver complications,⁶ and leaving behind a 6.5-inch clamp in a surgical incision.⁷

On the other hand, a Connecticut court (which decided the case in the hypothetical above) ruled that, under the facts, the defendant’s conduct did not meet the high threshold of egregiousness that defines gross negligence.⁸

As in any malpractice lawsuit, a medical board investigation involves determining whether the accused physician has met the standard of care in his or her specialty, and boards usually look to expert community physicians to articulate that requisite standard.

Compared with a civil lawsuit, a disciplinary hearing has the physician at a disadvantage. Medical board complaints are easier to file; the complaining party does not need an attorney; impartial expert witnesses are the responsibility of the board, not the complainant; and no patient injury needs to be shown.

Furthermore, a settlement is rarely reached or negotiated, and penalties are potentially far more serious, such as public posting of an adverse decision and restriction or actual loss of licensure.

Reputational loss also is arguably more devastating with board censure, because an adverse action taken by a medical board indicates a violation of the Medical Practice Act. In contrast, malpractice settlements or verdicts are regularly viewed as unreliable measures of a physician’s competence.

Still, two features work in favor of the doctor facing a board hearing. First, the misconduct typically has to be recurrent or grossly negligent, rather than an isolated case of carelessness. And second, some boards (only a small minority) require evidentiary proof of fault to be “clear and convincing,” instead of the familiar “more probable than not” standard that is used in a civil negligence suit. This makes it theoretically harder to reach a finding of culpability against the doctor.

References

1. Md. Code Ann. Health Occ. section 14-404.

2. Prosser and Keeton on Torts, 5th ed., 1984.

3. Van Meter v. Bent Construction Co., 297 P.2d 644 (Cal. 1956).

4. Texas Civil Practice & Remedies Code section 41.001(7).

5. Dempsey v. Phelps, 700 So.2d 1340 (Ala. 1997).

6. Jackson v. Taylor, 912 F.2d 795 (5th Cir. 1990).

7. Fox v. Oklahoma Memorial Hospital, 774 P.2d 459 (Ok. 1989).

8. Boone v. William W. Backus Hospital, 864 A.2d 1 (Conn. 2005).

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].

(This column is the second in a three-part series.)

Question: A penicillin-allergic patient died from massive hemolysis after receiving the antibiotic ceftriaxone (Rocephin). The plaintiff alleged that the defendant was grossly negligent in administering the drug and subsequently refusing to treat or to readmit the decedent.

If this case is referred to the state’s medical board, which of the following statements is best?

A. The outcome depends on the jurisdiction.

B. Substandard medical care is not part of professional misconduct, which is what a medical board is supposed to look at.

C. Disciplinary action requires a simple showing of ordinary negligence.

D. Disciplinary action requires more than one act of ordinary negligence.

E. Disciplinary action requires proof of gross negligence.

Answer: A. Under the Medical Practice Act, each state authorizes its medical board to issue licenses and regulate physician practice. Professional misconduct is about unprofessional behavior, and covers both ethical breach and substandard care.

Medical boards do not typically adjudicate single acts of ordinary negligence, leaving them instead to the tort system and civil lawsuits. However, grossly culpable misconduct – even in a single instance – or a recurring pattern of ordinary negligence can come under medical board review. And it is common practice for boards to use malpractice data as a tool to trigger further investigations, such as a certain number of malpractice settlements over a given span of time.

States vary somewhat over when to investigate a complaint of alleged substandard practice. In California, the term “unprofessional conduct” is codified under section 2234 of the California Business and Professions Code, and the errant doctor is subject to disciplinary sanction if there is gross negligence, repeated negligent acts (defined as two or more negligent acts or omissions), or incompetence.

In Hawaii, the disciplinary law is set up under Hawaii Revised Statutes section 453-8, which lists 15 situations of wrongdoing. In the malpractice category, Hawaii’s law uses the terms hazardous misconduct, hazardous negligence, incompetence, or multiple instances of negligence.

The state of New York defines professional misconduct by reference to a comprehensive list of 49 categories under section 6530, which include gross incompetence or gross negligence on a single occasion, or negligence or incompetence on more than one occasion.

However, Maryland is an example of a jurisdiction that does not require gross or repeated negligence; the state considers any failure to meet the appropriate medical standards as professional misconduct.¹

But what constitutes gross negligence?

The vast majority of medical malpractice lawsuits allege ordinary, not gross negligence. Ordinary negligence is a well-defined legal term, as illustrated in Prosser’s Textbook on Torts: “The formula under which this usually is put to the jury is that the doctor must have and use the knowledge, skill, and care ordinarily possessed and employed by members of the profession in good standing.”²

In contrast, there is no universal definition for the term gross negligence. Everyone recognizes it denotes a greater degree of culpability than ordinary negligence, but how much greater?

According to the California Supreme Court, gross negligence may be said to be “the want of even scant care or an extreme departure from the ordinary standard of conduct.”³ The law in Texas stipulates: “Gross negligence means more than momentary thoughtlessness, inadvertence, or error of judgment. It means an entire want of care as to establish that the act or omission was the result of actual, conscious indifference to the rights, safety, and welfare of the person affected.”⁴

Examples in case law of gross negligence (or where punitive damages were awarded, which usually signify egregious conduct) include a doctor’s wanton failure to provide follow-up care for a child who developed fever and gangrenous toes following foot surgery,⁵ the prescription of an excessive number of birth control pills (more than 1,000 pills within a time period when less than 200 were sufficient) with resulting liver complications,⁶ and leaving behind a 6.5-inch clamp in a surgical incision.⁷

On the other hand, a Connecticut court (which decided the case in the hypothetical above) ruled that, under the facts, the defendant’s conduct did not meet the high threshold of egregiousness that defines gross negligence.⁸

As in any malpractice lawsuit, a medical board investigation involves determining whether the accused physician has met the standard of care in his or her specialty, and boards usually look to expert community physicians to articulate that requisite standard.

Compared with a civil lawsuit, a disciplinary hearing has the physician at a disadvantage. Medical board complaints are easier to file; the complaining party does not need an attorney; impartial expert witnesses are the responsibility of the board, not the complainant; and no patient injury needs to be shown.

Furthermore, a settlement is rarely reached or negotiated, and penalties are potentially far more serious, such as public posting of an adverse decision and restriction or actual loss of licensure.

Reputational loss also is arguably more devastating with board censure, because an adverse action taken by a medical board indicates a violation of the Medical Practice Act. In contrast, malpractice settlements or verdicts are regularly viewed as unreliable measures of a physician’s competence.

Still, two features work in favor of the doctor facing a board hearing. First, the misconduct typically has to be recurrent or grossly negligent, rather than an isolated case of carelessness. And second, some boards (only a small minority) require evidentiary proof of fault to be “clear and convincing,” instead of the familiar “more probable than not” standard that is used in a civil negligence suit. This makes it theoretically harder to reach a finding of culpability against the doctor.

References

1. Md. Code Ann. Health Occ. section 14-404.

2. Prosser and Keeton on Torts, 5th ed., 1984.

3. Van Meter v. Bent Construction Co., 297 P.2d 644 (Cal. 1956).

4. Texas Civil Practice & Remedies Code section 41.001(7).

5. Dempsey v. Phelps, 700 So.2d 1340 (Ala. 1997).

6. Jackson v. Taylor, 912 F.2d 795 (5th Cir. 1990).

7. Fox v. Oklahoma Memorial Hospital, 774 P.2d 459 (Ok. 1989).

8. Boone v. William W. Backus Hospital, 864 A.2d 1 (Conn. 2005).

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at [email protected].