Photo from Business Wire

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) seeking approval for brentuximab vedotin (Adcetris) as a treatment for cutaneous T-cell lymphoma (CTCL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for brentuximab vedotin by December 16, 2017.

The sBLA is supported by data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

About brentuximab vedotin

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin is currently FDA-approved for 3 indications.

The drug is approved to treat patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates. Brentuximab vedotin initially had accelerated approval for this indication, but it was later converted to full approval.

Brentuximab vedotin also has full approval as consolidation for patients with classical Hodgkin lymphoma who have a high risk of relapse or progression after auto-HSCT.

And the drug has accelerated approval for the treatment of patients with systemic anaplastic large-cell lymphoma (sALCL) after failure of at least 1 prior multi-agent chemotherapy regimen. This accelerated approval is based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Brentuximab vedotin previously received breakthrough therapy designation from the FDA for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous ALCL who require systemic therapy and have received 1 prior systemic therapy.

Brentuximab vedotin also has orphan drug designation from the FDA for the treatment of MF.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) seeking approval for brentuximab vedotin (Adcetris) as a treatment for cutaneous T-cell lymphoma (CTCL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for brentuximab vedotin by December 16, 2017.

The sBLA is supported by data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

About brentuximab vedotin

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin is currently FDA-approved for 3 indications.

The drug is approved to treat patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates. Brentuximab vedotin initially had accelerated approval for this indication, but it was later converted to full approval.

Brentuximab vedotin also has full approval as consolidation for patients with classical Hodgkin lymphoma who have a high risk of relapse or progression after auto-HSCT.

And the drug has accelerated approval for the treatment of patients with systemic anaplastic large-cell lymphoma (sALCL) after failure of at least 1 prior multi-agent chemotherapy regimen. This accelerated approval is based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Brentuximab vedotin previously received breakthrough therapy designation from the FDA for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous ALCL who require systemic therapy and have received 1 prior systemic therapy.

Brentuximab vedotin also has orphan drug designation from the FDA for the treatment of MF.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) seeking approval for brentuximab vedotin (Adcetris) as a treatment for cutaneous T-cell lymphoma (CTCL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the sBLA for brentuximab vedotin by December 16, 2017.

The sBLA is supported by data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

About brentuximab vedotin

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin is currently FDA-approved for 3 indications.

The drug is approved to treat patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates. Brentuximab vedotin initially had accelerated approval for this indication, but it was later converted to full approval.

Brentuximab vedotin also has full approval as consolidation for patients with classical Hodgkin lymphoma who have a high risk of relapse or progression after auto-HSCT.

And the drug has accelerated approval for the treatment of patients with systemic anaplastic large-cell lymphoma (sALCL) after failure of at least 1 prior multi-agent chemotherapy regimen. This accelerated approval is based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Brentuximab vedotin previously received breakthrough therapy designation from the FDA for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous ALCL who require systemic therapy and have received 1 prior systemic therapy.

Brentuximab vedotin also has orphan drug designation from the FDA for the treatment of MF.

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has announced that Cook Medical Inc. is recalling the Zenith Alpha Thoracic Endovascular Graft.

The company found that when the device is used for the treatment of blunt traumatic aortic injury (BTAI), thrombi can form and the device can become occluded. This can lead to serious adverse events, including death.

There have been 5 reports of thrombosis/occlusion with this product, all in patients treated for BTAI. In 1 case, a patient died.

Therefore, Cook Medical Inc. is recalling all lots of the Zenith Alpha Thoracic Endovascular Graft that were manufactured from April 10, 2015, to January 3, 2017, and distributed from October 29, 2015, to March 10, 2017.

On March 22, 2017, Cook Medical Inc. sent an “Urgent: Medical Device Correction and Removal” notification to all affected customers.

This recall notification included a description of the problem and reason for the recall, list of affected products, and customer actions to be taken in response to the recall notification.

On June 22, 2017, the company sent an updated notification to all affected customers.

This recall notification informed customers that the instructions for use (IFU) for the Zenith Alpha Thoracic Endovascular Graft were updated to remove the indication for BTAI.

Because of the IFU correction to remove BTAI from the indication, it is necessary to remove specific sizes of this device (grafts with a proximal or distal diameter of 18-22 mm) that would likely be used only for BTAI.

About 500 of these devices (18 to 22 mm) will be removed, and roughly 4500 will be relabeled. A Cook Medical sales representative will follow-up with affected customers and provide a corrected IFU.

The company recommends that patients already treated with the Zenith Thoracic Endovascular Graft for the BTAI indication be followed according the current IFU and with considerations outlined in Cook Medical’s March 22, 2017, medical device correction notification.

Customers with questions about this recall may contact Cook Medical Customer Relations at 800-457-4500 or 812-339-2235.

Healthcare professionals and patients are encouraged to report adverse events related to the Zenith Thoracic Endovascular Graft to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has announced that Cook Medical Inc. is recalling the Zenith Alpha Thoracic Endovascular Graft.

The company found that when the device is used for the treatment of blunt traumatic aortic injury (BTAI), thrombi can form and the device can become occluded. This can lead to serious adverse events, including death.

There have been 5 reports of thrombosis/occlusion with this product, all in patients treated for BTAI. In 1 case, a patient died.

Therefore, Cook Medical Inc. is recalling all lots of the Zenith Alpha Thoracic Endovascular Graft that were manufactured from April 10, 2015, to January 3, 2017, and distributed from October 29, 2015, to March 10, 2017.

On March 22, 2017, Cook Medical Inc. sent an “Urgent: Medical Device Correction and Removal” notification to all affected customers.

This recall notification included a description of the problem and reason for the recall, list of affected products, and customer actions to be taken in response to the recall notification.

On June 22, 2017, the company sent an updated notification to all affected customers.

This recall notification informed customers that the instructions for use (IFU) for the Zenith Alpha Thoracic Endovascular Graft were updated to remove the indication for BTAI.

Because of the IFU correction to remove BTAI from the indication, it is necessary to remove specific sizes of this device (grafts with a proximal or distal diameter of 18-22 mm) that would likely be used only for BTAI.

About 500 of these devices (18 to 22 mm) will be removed, and roughly 4500 will be relabeled. A Cook Medical sales representative will follow-up with affected customers and provide a corrected IFU.

The company recommends that patients already treated with the Zenith Thoracic Endovascular Graft for the BTAI indication be followed according the current IFU and with considerations outlined in Cook Medical’s March 22, 2017, medical device correction notification.

Customers with questions about this recall may contact Cook Medical Customer Relations at 800-457-4500 or 812-339-2235.

Healthcare professionals and patients are encouraged to report adverse events related to the Zenith Thoracic Endovascular Graft to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

Image by Kevin MacKenzie

The US Food and Drug Administration (FDA) has announced that Cook Medical Inc. is recalling the Zenith Alpha Thoracic Endovascular Graft.

The company found that when the device is used for the treatment of blunt traumatic aortic injury (BTAI), thrombi can form and the device can become occluded. This can lead to serious adverse events, including death.

There have been 5 reports of thrombosis/occlusion with this product, all in patients treated for BTAI. In 1 case, a patient died.

Therefore, Cook Medical Inc. is recalling all lots of the Zenith Alpha Thoracic Endovascular Graft that were manufactured from April 10, 2015, to January 3, 2017, and distributed from October 29, 2015, to March 10, 2017.

On March 22, 2017, Cook Medical Inc. sent an “Urgent: Medical Device Correction and Removal” notification to all affected customers.

This recall notification included a description of the problem and reason for the recall, list of affected products, and customer actions to be taken in response to the recall notification.

On June 22, 2017, the company sent an updated notification to all affected customers.

This recall notification informed customers that the instructions for use (IFU) for the Zenith Alpha Thoracic Endovascular Graft were updated to remove the indication for BTAI.

Because of the IFU correction to remove BTAI from the indication, it is necessary to remove specific sizes of this device (grafts with a proximal or distal diameter of 18-22 mm) that would likely be used only for BTAI.

About 500 of these devices (18 to 22 mm) will be removed, and roughly 4500 will be relabeled. A Cook Medical sales representative will follow-up with affected customers and provide a corrected IFU.

The company recommends that patients already treated with the Zenith Thoracic Endovascular Graft for the BTAI indication be followed according the current IFU and with considerations outlined in Cook Medical’s March 22, 2017, medical device correction notification.

Customers with questions about this recall may contact Cook Medical Customer Relations at 800-457-4500 or 812-339-2235.

Healthcare professionals and patients are encouraged to report adverse events related to the Zenith Thoracic Endovascular Graft to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

Based on the negative KOH and the nail pits, the FP made a diagnosis of plaque psoriasis. This condition can present in an annular pattern resembling tinea corporis. The combination of negative KOH and nail pits are enough to diagnose plaque psoriasis without a biopsy. Otherwise, a 4-mm punch biopsy of the area with erythema and scale would confirm the diagnosis.

Plaque psoriasis is typically treated using a mid- to high-potency topical steroid. Although repeated use of steroids in cases of atopic dermatitis can lead to skin atrophy, this is less common when treating psoriasis. If skin atrophy is still a concern, an alternative to topical steroids is a topical vitamin D preparation.

Vitamin D preparations are typically more expensive than steroids and require prior authorization, but there is one generic preparation (calcipotriene) that is more affordable than its brand-name counterparts. Another nonsystemic treatment to consider when treating plaque psoriasis without psoriatic arthritis is narrowband ultraviolet B therapy.

One risk factor for psoriasis is being overweight. In this case, the FP counseled the patient on weight loss. The FP then prescribed 0.1% triamcinolone ointment to be applied twice daily (especially after bathing).

At a follow-up appointment a month later, there was about 70% clearance of the lesions. For the stubborn areas, the FP prescribed a higher-potency steroid, 0.05% clobetasol ointment, to be applied twice daily. As the cost of clobetasol has risen over the past 2 years, alternatives that may be covered by insurance include augmented betamethasone and halobetasol.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the negative KOH and the nail pits, the FP made a diagnosis of plaque psoriasis. This condition can present in an annular pattern resembling tinea corporis. The combination of negative KOH and nail pits are enough to diagnose plaque psoriasis without a biopsy. Otherwise, a 4-mm punch biopsy of the area with erythema and scale would confirm the diagnosis.

Plaque psoriasis is typically treated using a mid- to high-potency topical steroid. Although repeated use of steroids in cases of atopic dermatitis can lead to skin atrophy, this is less common when treating psoriasis. If skin atrophy is still a concern, an alternative to topical steroids is a topical vitamin D preparation.

Vitamin D preparations are typically more expensive than steroids and require prior authorization, but there is one generic preparation (calcipotriene) that is more affordable than its brand-name counterparts. Another nonsystemic treatment to consider when treating plaque psoriasis without psoriatic arthritis is narrowband ultraviolet B therapy.

One risk factor for psoriasis is being overweight. In this case, the FP counseled the patient on weight loss. The FP then prescribed 0.1% triamcinolone ointment to be applied twice daily (especially after bathing).

At a follow-up appointment a month later, there was about 70% clearance of the lesions. For the stubborn areas, the FP prescribed a higher-potency steroid, 0.05% clobetasol ointment, to be applied twice daily. As the cost of clobetasol has risen over the past 2 years, alternatives that may be covered by insurance include augmented betamethasone and halobetasol.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the negative KOH and the nail pits, the FP made a diagnosis of plaque psoriasis. This condition can present in an annular pattern resembling tinea corporis. The combination of negative KOH and nail pits are enough to diagnose plaque psoriasis without a biopsy. Otherwise, a 4-mm punch biopsy of the area with erythema and scale would confirm the diagnosis.

Plaque psoriasis is typically treated using a mid- to high-potency topical steroid. Although repeated use of steroids in cases of atopic dermatitis can lead to skin atrophy, this is less common when treating psoriasis. If skin atrophy is still a concern, an alternative to topical steroids is a topical vitamin D preparation.

Vitamin D preparations are typically more expensive than steroids and require prior authorization, but there is one generic preparation (calcipotriene) that is more affordable than its brand-name counterparts. Another nonsystemic treatment to consider when treating plaque psoriasis without psoriatic arthritis is narrowband ultraviolet B therapy.

One risk factor for psoriasis is being overweight. In this case, the FP counseled the patient on weight loss. The FP then prescribed 0.1% triamcinolone ointment to be applied twice daily (especially after bathing).

At a follow-up appointment a month later, there was about 70% clearance of the lesions. For the stubborn areas, the FP prescribed a higher-potency steroid, 0.05% clobetasol ointment, to be applied twice daily. As the cost of clobetasol has risen over the past 2 years, alternatives that may be covered by insurance include augmented betamethasone and halobetasol.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Polyphenols are well known as the largest group of and most widely distributed phytochemicals among plants.¹ These secondary plant metabolites, which are produced in response to environmental hazards that contribute to free-radical synthesis,² are represented by more than 8,000 naturally occurring compounds. This family of widely divergent substances has gained increasing attention in recent years as polyphenols have been found – in vegetables, fruits, herbs, grains, tea, coffee beans, honey, and red wine – to be the most abundant sources of antioxidants in the human diet and are known to exert antioxidant, anti-inflammatory, and antimicrobial benefits to human health.^3-7 The most prevalent and studied polyphenols are known as flavonoids, but nonflavonoid polyphenols are increasingly well investigated. This column will address the basic chemistry of these compounds. Subsequent columns will discuss the latest research on the cutaneous benefits of selected flavonoid and nonflavonoid polyphenols.

Lukzs/Thinkstock

Chemistry and sources

Polyphenols share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl, methyl, or acetyl group linked via a three-carbon bond to form a six-unit heterocyclic ring.^8,9 When the “parent polyphenol” known as cinnamic acid is further catalytically transformed, scores of polyphenolic compounds result. These substances are divided into classes: glycosylated phenylpropanoids, flavonoids, isoflavonoids, stilbenoids, coumarins, curcuminoids, as well as phenolic polymers such as tannins, proanthocyanidins, suberin, lignins, and lignans. The flavonoids, which are the largest and most varied phenolic substances in plants, can be further divided into several categories: flavones (based on the 2-phenylchromen-4-one skeleton, such as apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, such as quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, such as naringenin, hesperidin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, such as genistein and daidzein); flavanols – also known as flavan-3-ols or catechins – (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, such as epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, and gallocatechin); and anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin).^5,10

The broader category of nonflavonoid polyphenols is rich and diverse, but is particularly noted for comprising the tannins, phenolic polymers of high molecular weight, which are divided into three classes, hydrolyzable tannins (such as ellagic acid, found in pomegranate, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in, for example, black and oolong teas), and condensed tannins (or proanthocyanidins, which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanin).1^,4,5,8,10 There are a plethora of other nonflavonoid polyphenols, many of which confer health benefits, including stilbenes (such as resveratrol, found in red wine), lignans (such as enterodiol, found in flaxseed and flaxseed oil), lignins (found in green beans, carrots, peas, and Brazil nuts), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods. In fact, hydroxycinnamic acids, which are the most common phenolic acids present in plant tissues, are present in numerous foods, such as apples, pears, plums, cherries, apricots, peaches, black currant, blueberries, potatoes, spinach, lettuce, cabbage, broccoli, asparagus, wine, and coffee.⁹

Conclusion

While the classification system for the 8,000 polyphenolic compounds may seem intimidating, the same essential activity is conferred by these abundant substances. Further, it is important to note the significant health benefits potentially derived from the oral consumption as well as topical application of polyphenols. The next two columns will delve into the research findings of flavonoid and nonflavonoid polyphenols.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. J Am Diet Assoc. 1999 Feb;99(2):213-8.

2. Ann N Y Acad Sci. 2012 Jul;1259:77-86.

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

4. J Nutr. 2000 Aug;130(8S Suppl):2073S-85S.

5. Annu Rev Nutr. 2002;22:19-34.

6. Pharmacol Ther. 2001 May-Jun;90(2-3):157-77.

7. Free Radic Biol Med. 2001 Jun 1;30(11):1213-22.

8. J Nutr. 2003 Oct;133(10):3248S-3254S.

9. Int J Mol Sci. 2016 Feb 18;17(2):160.

10. Asia Pac J Clin Nutr. 2004;13(Suppl):S72, 2004.

Polyphenols are well known as the largest group of and most widely distributed phytochemicals among plants.¹ These secondary plant metabolites, which are produced in response to environmental hazards that contribute to free-radical synthesis,² are represented by more than 8,000 naturally occurring compounds. This family of widely divergent substances has gained increasing attention in recent years as polyphenols have been found – in vegetables, fruits, herbs, grains, tea, coffee beans, honey, and red wine – to be the most abundant sources of antioxidants in the human diet and are known to exert antioxidant, anti-inflammatory, and antimicrobial benefits to human health.^3-7 The most prevalent and studied polyphenols are known as flavonoids, but nonflavonoid polyphenols are increasingly well investigated. This column will address the basic chemistry of these compounds. Subsequent columns will discuss the latest research on the cutaneous benefits of selected flavonoid and nonflavonoid polyphenols.

Lukzs/Thinkstock

Chemistry and sources

Polyphenols share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl, methyl, or acetyl group linked via a three-carbon bond to form a six-unit heterocyclic ring.^8,9 When the “parent polyphenol” known as cinnamic acid is further catalytically transformed, scores of polyphenolic compounds result. These substances are divided into classes: glycosylated phenylpropanoids, flavonoids, isoflavonoids, stilbenoids, coumarins, curcuminoids, as well as phenolic polymers such as tannins, proanthocyanidins, suberin, lignins, and lignans. The flavonoids, which are the largest and most varied phenolic substances in plants, can be further divided into several categories: flavones (based on the 2-phenylchromen-4-one skeleton, such as apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, such as quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, such as naringenin, hesperidin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, such as genistein and daidzein); flavanols – also known as flavan-3-ols or catechins – (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, such as epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, and gallocatechin); and anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin).^5,10

The broader category of nonflavonoid polyphenols is rich and diverse, but is particularly noted for comprising the tannins, phenolic polymers of high molecular weight, which are divided into three classes, hydrolyzable tannins (such as ellagic acid, found in pomegranate, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in, for example, black and oolong teas), and condensed tannins (or proanthocyanidins, which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanin).1^,4,5,8,10 There are a plethora of other nonflavonoid polyphenols, many of which confer health benefits, including stilbenes (such as resveratrol, found in red wine), lignans (such as enterodiol, found in flaxseed and flaxseed oil), lignins (found in green beans, carrots, peas, and Brazil nuts), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods. In fact, hydroxycinnamic acids, which are the most common phenolic acids present in plant tissues, are present in numerous foods, such as apples, pears, plums, cherries, apricots, peaches, black currant, blueberries, potatoes, spinach, lettuce, cabbage, broccoli, asparagus, wine, and coffee.⁹

Conclusion

While the classification system for the 8,000 polyphenolic compounds may seem intimidating, the same essential activity is conferred by these abundant substances. Further, it is important to note the significant health benefits potentially derived from the oral consumption as well as topical application of polyphenols. The next two columns will delve into the research findings of flavonoid and nonflavonoid polyphenols.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. J Am Diet Assoc. 1999 Feb;99(2):213-8.

2. Ann N Y Acad Sci. 2012 Jul;1259:77-86.

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

4. J Nutr. 2000 Aug;130(8S Suppl):2073S-85S.

5. Annu Rev Nutr. 2002;22:19-34.

6. Pharmacol Ther. 2001 May-Jun;90(2-3):157-77.

7. Free Radic Biol Med. 2001 Jun 1;30(11):1213-22.

8. J Nutr. 2003 Oct;133(10):3248S-3254S.

9. Int J Mol Sci. 2016 Feb 18;17(2):160.

10. Asia Pac J Clin Nutr. 2004;13(Suppl):S72, 2004.

Polyphenols are well known as the largest group of and most widely distributed phytochemicals among plants.¹ These secondary plant metabolites, which are produced in response to environmental hazards that contribute to free-radical synthesis,² are represented by more than 8,000 naturally occurring compounds. This family of widely divergent substances has gained increasing attention in recent years as polyphenols have been found – in vegetables, fruits, herbs, grains, tea, coffee beans, honey, and red wine – to be the most abundant sources of antioxidants in the human diet and are known to exert antioxidant, anti-inflammatory, and antimicrobial benefits to human health.^3-7 The most prevalent and studied polyphenols are known as flavonoids, but nonflavonoid polyphenols are increasingly well investigated. This column will address the basic chemistry of these compounds. Subsequent columns will discuss the latest research on the cutaneous benefits of selected flavonoid and nonflavonoid polyphenols.

Lukzs/Thinkstock

Chemistry and sources

Polyphenols share a common structural component: a phenol or an aromatic ring, usually two, with at least one hydroxyl, methyl, or acetyl group linked via a three-carbon bond to form a six-unit heterocyclic ring.^8,9 When the “parent polyphenol” known as cinnamic acid is further catalytically transformed, scores of polyphenolic compounds result. These substances are divided into classes: glycosylated phenylpropanoids, flavonoids, isoflavonoids, stilbenoids, coumarins, curcuminoids, as well as phenolic polymers such as tannins, proanthocyanidins, suberin, lignins, and lignans. The flavonoids, which are the largest and most varied phenolic substances in plants, can be further divided into several categories: flavones (based on the 2-phenylchromen-4-one skeleton, such as apigenin and luteolin); flavonols (based on the 3-hydroxy-2-phenylchromen-4-one skeleton and functional group, such as quercetin, kaempferol, myricetin, and fisetin); flavanones (based on the 2,3-dihydro-2-phenylchromen-4-one skeleton and functional group, such as naringenin, hesperidin, and eriodictyol); isoflavones (based on the 3-phenylchromen-4-one skeleton, such as genistein and daidzein); flavanols – also known as flavan-3-ols or catechins – (based on the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton and functional groups, such as epicatechin, epicatechin 3-gallate, epigallocatechin, epigallocatechin 3-gallate (EGCG), catechin, and gallocatechin); and anthocyanins (based on the 2-phenylchromenylium ion skeleton, e.g., cyanidin and pelargonidin).^5,10

The broader category of nonflavonoid polyphenols is rich and diverse, but is particularly noted for comprising the tannins, phenolic polymers of high molecular weight, which are divided into three classes, hydrolyzable tannins (such as ellagic acid, found in pomegranate, raspberries, strawberries, cranberries, and walnuts), derived tannins (created during food handling and processing and present in, for example, black and oolong teas), and condensed tannins (or proanthocyanidins, which are polymer chains of flavanols, such as catechins, and include pycnogenol, leukocyanidin, and leucoanthocyanin).1^,4,5,8,10 There are a plethora of other nonflavonoid polyphenols, many of which confer health benefits, including stilbenes (such as resveratrol, found in red wine), lignans (such as enterodiol, found in flaxseed and flaxseed oil), lignins (found in green beans, carrots, peas, and Brazil nuts), and phenolic acids, such as hydroxybenzoic and hydroxycinnamic acids, among which caffeic and ferulic acids are often present in foods. In fact, hydroxycinnamic acids, which are the most common phenolic acids present in plant tissues, are present in numerous foods, such as apples, pears, plums, cherries, apricots, peaches, black currant, blueberries, potatoes, spinach, lettuce, cabbage, broccoli, asparagus, wine, and coffee.⁹

Conclusion

While the classification system for the 8,000 polyphenolic compounds may seem intimidating, the same essential activity is conferred by these abundant substances. Further, it is important to note the significant health benefits potentially derived from the oral consumption as well as topical application of polyphenols. The next two columns will delve into the research findings of flavonoid and nonflavonoid polyphenols.

Dr. Baumann is a private practice dermatologist, researcher, author and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. J Am Diet Assoc. 1999 Feb;99(2):213-8.

2. Ann N Y Acad Sci. 2012 Jul;1259:77-86.

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

4. J Nutr. 2000 Aug;130(8S Suppl):2073S-85S.

5. Annu Rev Nutr. 2002;22:19-34.

6. Pharmacol Ther. 2001 May-Jun;90(2-3):157-77.

7. Free Radic Biol Med. 2001 Jun 1;30(11):1213-22.

8. J Nutr. 2003 Oct;133(10):3248S-3254S.

9. Int J Mol Sci. 2016 Feb 18;17(2):160.

10. Asia Pac J Clin Nutr. 2004;13(Suppl):S72, 2004.

Compared with adults who underwent off-pump coronary-artery bypass grafting surgery, those who underwent on-pump CABG had significantly lower rates of mortality and major adverse cardiovascular events at 5 years, results from a large randomized trial demonstrated.

“Given the results, it appears that innovative surgical approaches – such as the more technically demanding off-pump procedure – may not always provide superior clinical outcomes,” researchers led by A. Laurie Shroyer, PhD, wrote (N Engl J Med. 2017 Aug 17;377:623-32). “Additional long-term follow-up, evaluating these same outcomes rigorously at 10 years after CABG, appears to be warranted. Future research may identify the risk factors of the patients and the cardiac surgical processes of care that affect longer-term outcomes of coronary revascularization procedures, with the goal of increasing the rate of long-term event-free survival.”

Dr. Shroyer, of the Northport (N.Y.) VA Medical Center, and her associates conduced a 5-year follow-up study of patients who had participated in the original Randomized On/Off Bypass (ROOBY) trial, which compared the effectiveness of the two surgical approaches (N Engl J Med 2009 Nov 5;361:1827-37). During February 2002–June 2007, 2,203 patients at 18 medical centers were randomly assigned to either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The primary outcomes were the rates mortality and major adverse cardiovascular events at 5 years, while the secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction.

The mean age of patients was 63 years, nearly all were male, 46% were between the ages of 55 and 64, and about 21% had chronic obstructive pulmonary disease. The researchers found that at 5 years, the rate of death was 15.2% in the off-pump group, compared with 11.9% in the on-pump group, which translated into a relative risk of 1.28 (P = .02). In addition, the rate of major cardiovascular events at 5 years was 31% in the off-pump group, compared with 27.1% in the on-pump group, which translated into a relative risk of 1.14 (P = .046). None of the secondary outcomes at 5 years met the prespecified threshold of a P value of .01 or less for statistical significance, when the off-pump and on-pump groups were compared. This included the rates of nonfatal myocardial infarction (12.1% vs. 9.6%, respectively; P = .05); death from cardiac causes (6.3% vs. 5.3%; P = .29); repeat vascularization (13.1% vs. 11.9%; P = .39), and repeat CABG (1.4% vs. 0.5%; P = .02).

“In combination with findings from other randomized trials and a 2012 Cochrane systematic review [Cochrane Database Syst Rev. 2012;14:CD007224], the 5-year outcomes in our study support the conclusion that off-pump CABG does not offer any substantial advantages over on-pump CABG except possibly in unusual situations such as, for example, in patients with an extensively calcified (porcelain) aorta, in whom the off-pump technique may result in less manipulation of the aorta, potentially decreasing the risk of aortic emboli or stroke,” the researchers wrote. “In light of the low rates of use of off-pump CABG in the United States, the findings in our trial may provide more of a real-world experience than those in the CORONARY and GOPCABE trials, which required surgeons with a very high volume of experience with off-pump procedures, as compared with the ROOBY trial and with most other surgeons who are based in the United States.”

They acknowledged certain limitations of the study, including the fact that the study population comprised mostly males who had multiple coexisting conditions, “so the findings may not be applicable to female patients or to patients who are not veterans.”

The study was supported by a grant from the Department of Veterans Affairs. Dr. Shroyer reported having received grants from the VA Cooperative Studies Program during the conduct of the study. Her coauthors reported having no financial disclosures.

[email protected]

Compared with adults who underwent off-pump coronary-artery bypass grafting surgery, those who underwent on-pump CABG had significantly lower rates of mortality and major adverse cardiovascular events at 5 years, results from a large randomized trial demonstrated.

“Given the results, it appears that innovative surgical approaches – such as the more technically demanding off-pump procedure – may not always provide superior clinical outcomes,” researchers led by A. Laurie Shroyer, PhD, wrote (N Engl J Med. 2017 Aug 17;377:623-32). “Additional long-term follow-up, evaluating these same outcomes rigorously at 10 years after CABG, appears to be warranted. Future research may identify the risk factors of the patients and the cardiac surgical processes of care that affect longer-term outcomes of coronary revascularization procedures, with the goal of increasing the rate of long-term event-free survival.”

Dr. Shroyer, of the Northport (N.Y.) VA Medical Center, and her associates conduced a 5-year follow-up study of patients who had participated in the original Randomized On/Off Bypass (ROOBY) trial, which compared the effectiveness of the two surgical approaches (N Engl J Med 2009 Nov 5;361:1827-37). During February 2002–June 2007, 2,203 patients at 18 medical centers were randomly assigned to either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The primary outcomes were the rates mortality and major adverse cardiovascular events at 5 years, while the secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction.

The mean age of patients was 63 years, nearly all were male, 46% were between the ages of 55 and 64, and about 21% had chronic obstructive pulmonary disease. The researchers found that at 5 years, the rate of death was 15.2% in the off-pump group, compared with 11.9% in the on-pump group, which translated into a relative risk of 1.28 (P = .02). In addition, the rate of major cardiovascular events at 5 years was 31% in the off-pump group, compared with 27.1% in the on-pump group, which translated into a relative risk of 1.14 (P = .046). None of the secondary outcomes at 5 years met the prespecified threshold of a P value of .01 or less for statistical significance, when the off-pump and on-pump groups were compared. This included the rates of nonfatal myocardial infarction (12.1% vs. 9.6%, respectively; P = .05); death from cardiac causes (6.3% vs. 5.3%; P = .29); repeat vascularization (13.1% vs. 11.9%; P = .39), and repeat CABG (1.4% vs. 0.5%; P = .02).

“In combination with findings from other randomized trials and a 2012 Cochrane systematic review [Cochrane Database Syst Rev. 2012;14:CD007224], the 5-year outcomes in our study support the conclusion that off-pump CABG does not offer any substantial advantages over on-pump CABG except possibly in unusual situations such as, for example, in patients with an extensively calcified (porcelain) aorta, in whom the off-pump technique may result in less manipulation of the aorta, potentially decreasing the risk of aortic emboli or stroke,” the researchers wrote. “In light of the low rates of use of off-pump CABG in the United States, the findings in our trial may provide more of a real-world experience than those in the CORONARY and GOPCABE trials, which required surgeons with a very high volume of experience with off-pump procedures, as compared with the ROOBY trial and with most other surgeons who are based in the United States.”

They acknowledged certain limitations of the study, including the fact that the study population comprised mostly males who had multiple coexisting conditions, “so the findings may not be applicable to female patients or to patients who are not veterans.”

The study was supported by a grant from the Department of Veterans Affairs. Dr. Shroyer reported having received grants from the VA Cooperative Studies Program during the conduct of the study. Her coauthors reported having no financial disclosures.

[email protected]

Compared with adults who underwent off-pump coronary-artery bypass grafting surgery, those who underwent on-pump CABG had significantly lower rates of mortality and major adverse cardiovascular events at 5 years, results from a large randomized trial demonstrated.

“Given the results, it appears that innovative surgical approaches – such as the more technically demanding off-pump procedure – may not always provide superior clinical outcomes,” researchers led by A. Laurie Shroyer, PhD, wrote (N Engl J Med. 2017 Aug 17;377:623-32). “Additional long-term follow-up, evaluating these same outcomes rigorously at 10 years after CABG, appears to be warranted. Future research may identify the risk factors of the patients and the cardiac surgical processes of care that affect longer-term outcomes of coronary revascularization procedures, with the goal of increasing the rate of long-term event-free survival.”

Dr. Shroyer, of the Northport (N.Y.) VA Medical Center, and her associates conduced a 5-year follow-up study of patients who had participated in the original Randomized On/Off Bypass (ROOBY) trial, which compared the effectiveness of the two surgical approaches (N Engl J Med 2009 Nov 5;361:1827-37). During February 2002–June 2007, 2,203 patients at 18 medical centers were randomly assigned to either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The primary outcomes were the rates mortality and major adverse cardiovascular events at 5 years, while the secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction.

The mean age of patients was 63 years, nearly all were male, 46% were between the ages of 55 and 64, and about 21% had chronic obstructive pulmonary disease. The researchers found that at 5 years, the rate of death was 15.2% in the off-pump group, compared with 11.9% in the on-pump group, which translated into a relative risk of 1.28 (P = .02). In addition, the rate of major cardiovascular events at 5 years was 31% in the off-pump group, compared with 27.1% in the on-pump group, which translated into a relative risk of 1.14 (P = .046). None of the secondary outcomes at 5 years met the prespecified threshold of a P value of .01 or less for statistical significance, when the off-pump and on-pump groups were compared. This included the rates of nonfatal myocardial infarction (12.1% vs. 9.6%, respectively; P = .05); death from cardiac causes (6.3% vs. 5.3%; P = .29); repeat vascularization (13.1% vs. 11.9%; P = .39), and repeat CABG (1.4% vs. 0.5%; P = .02).

“In combination with findings from other randomized trials and a 2012 Cochrane systematic review [Cochrane Database Syst Rev. 2012;14:CD007224], the 5-year outcomes in our study support the conclusion that off-pump CABG does not offer any substantial advantages over on-pump CABG except possibly in unusual situations such as, for example, in patients with an extensively calcified (porcelain) aorta, in whom the off-pump technique may result in less manipulation of the aorta, potentially decreasing the risk of aortic emboli or stroke,” the researchers wrote. “In light of the low rates of use of off-pump CABG in the United States, the findings in our trial may provide more of a real-world experience than those in the CORONARY and GOPCABE trials, which required surgeons with a very high volume of experience with off-pump procedures, as compared with the ROOBY trial and with most other surgeons who are based in the United States.”

They acknowledged certain limitations of the study, including the fact that the study population comprised mostly males who had multiple coexisting conditions, “so the findings may not be applicable to female patients or to patients who are not veterans.”

The study was supported by a grant from the Department of Veterans Affairs. Dr. Shroyer reported having received grants from the VA Cooperative Studies Program during the conduct of the study. Her coauthors reported having no financial disclosures.

[email protected]

A new study finds tele-neurology visits are just as effective as in-person visits for patients with Parkinson’s disease, while also saving time and mileage.

Lead author Christopher A. Beck, PhD, of the University of Rochester (N.Y.), and his colleagues studied 195 patients for 1 year who were either provided with their usual medical care or their usual medical care supplemented by four virtual visits via video conferencing from a remote specialist. Investigators evaluated the feasibility of telemedicine visits, as measured by the proportion of patients who completed at least one virtual visit and the proportion of virtual visits completed on time. Efficacy was also evaluated, as measured by the change in the Parkinson’s Disease Questionnaire–39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings.

Eligible participants had a clinical diagnosis of Parkinson’s disease, had a private, Internet-enabled device, and lived in a state where a site investigator was licensed to practice. Patients randomized to the telemedicine group received up to four virtual visits over 12 months from a neurologist. Physicians and patients determined the specific content and frequency of each visit, but the format generally included a medical history, a Parkinson’s disease–specific examination (including assessment of tremor and gait), physician recommendations, and time to address patients’ concerns (Neurology. 2017 Aug 16. doi: 10.1212/WNL.0000000000004357).

The study findings showed that the virtual house calls were as effective as were in-person visits, with quality of life no better or worse for patients receiving care at home than for those receiving care in the office. Of telemedicine patients, 98% completed at least one virtual visit, and 91% of all virtual visits scheduled were completed. Researchers also found that participants’ overall quality of care and the burden felt by caregivers was no different whether they had virtual or in-person visits. Each virtual house call saved patients a median of 88 minutes and 38 miles per visit.

Ninety-seven percent of patients and 86% of participating neurologists said they were satisfied with the virtual visits, with 55% of patients stating they preferred virtual visits over in-person visits.

The study – the first national randomized controlled trial of telemedicine to connect remote specialists to patients at home – shows that tele-neurology is a practical and effective model of care for Parkinson patients, said study coauthor E. Ray Dorsey, MD, of the University of Rochester.

“People were very interested in taking part in this study, and the results showed that these virtual house calls were feasible for people with Parkinson’s disease,” Dr. Dorsey said in a statement. “People’s care was as effective as with the in-office visits, and the virtual house calls provided the participants with convenience and comfort.”

Dr. Dorsey noted that 73% of the study participants had visited a Parkinson’s disease specialist in the past year and 83% said they were satisfied with their care, which may have impacted the quality of life finding.

“The fact that adding the virtual house calls to people’s care did not improve their quality of life could be because a large proportion were already seeing a specialist and were satisfied with that care,” he said. “Of course, it’s also possible that virtual house calls are not enough to improve quality of life.”

Limitations of the study included that study participants were primarily well-educated and more familiar with the Internet than was the general population, so results may not be relevant for all people with Parkinson’s disease. In addition, the study population, of whom 96% were white with a mean age of 66 years, did not include people with the disease who live in nursing homes, who account for nearly 25% of all Medicare beneficiaries with Parkinson’s disease.

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Dorsey serves on the medical advisory board of, and has stock options in, Grand Rounds. No other relevant disclosures relevant were reported by study authors.

[email protected]

On Twitter @legal_med

A new study finds tele-neurology visits are just as effective as in-person visits for patients with Parkinson’s disease, while also saving time and mileage.

Lead author Christopher A. Beck, PhD, of the University of Rochester (N.Y.), and his colleagues studied 195 patients for 1 year who were either provided with their usual medical care or their usual medical care supplemented by four virtual visits via video conferencing from a remote specialist. Investigators evaluated the feasibility of telemedicine visits, as measured by the proportion of patients who completed at least one virtual visit and the proportion of virtual visits completed on time. Efficacy was also evaluated, as measured by the change in the Parkinson’s Disease Questionnaire–39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings.

Eligible participants had a clinical diagnosis of Parkinson’s disease, had a private, Internet-enabled device, and lived in a state where a site investigator was licensed to practice. Patients randomized to the telemedicine group received up to four virtual visits over 12 months from a neurologist. Physicians and patients determined the specific content and frequency of each visit, but the format generally included a medical history, a Parkinson’s disease–specific examination (including assessment of tremor and gait), physician recommendations, and time to address patients’ concerns (Neurology. 2017 Aug 16. doi: 10.1212/WNL.0000000000004357).

The study findings showed that the virtual house calls were as effective as were in-person visits, with quality of life no better or worse for patients receiving care at home than for those receiving care in the office. Of telemedicine patients, 98% completed at least one virtual visit, and 91% of all virtual visits scheduled were completed. Researchers also found that participants’ overall quality of care and the burden felt by caregivers was no different whether they had virtual or in-person visits. Each virtual house call saved patients a median of 88 minutes and 38 miles per visit.

Ninety-seven percent of patients and 86% of participating neurologists said they were satisfied with the virtual visits, with 55% of patients stating they preferred virtual visits over in-person visits.

The study – the first national randomized controlled trial of telemedicine to connect remote specialists to patients at home – shows that tele-neurology is a practical and effective model of care for Parkinson patients, said study coauthor E. Ray Dorsey, MD, of the University of Rochester.

“People were very interested in taking part in this study, and the results showed that these virtual house calls were feasible for people with Parkinson’s disease,” Dr. Dorsey said in a statement. “People’s care was as effective as with the in-office visits, and the virtual house calls provided the participants with convenience and comfort.”

Dr. Dorsey noted that 73% of the study participants had visited a Parkinson’s disease specialist in the past year and 83% said they were satisfied with their care, which may have impacted the quality of life finding.

“The fact that adding the virtual house calls to people’s care did not improve their quality of life could be because a large proportion were already seeing a specialist and were satisfied with that care,” he said. “Of course, it’s also possible that virtual house calls are not enough to improve quality of life.”

Limitations of the study included that study participants were primarily well-educated and more familiar with the Internet than was the general population, so results may not be relevant for all people with Parkinson’s disease. In addition, the study population, of whom 96% were white with a mean age of 66 years, did not include people with the disease who live in nursing homes, who account for nearly 25% of all Medicare beneficiaries with Parkinson’s disease.

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Dorsey serves on the medical advisory board of, and has stock options in, Grand Rounds. No other relevant disclosures relevant were reported by study authors.

[email protected]

On Twitter @legal_med

A new study finds tele-neurology visits are just as effective as in-person visits for patients with Parkinson’s disease, while also saving time and mileage.

Lead author Christopher A. Beck, PhD, of the University of Rochester (N.Y.), and his colleagues studied 195 patients for 1 year who were either provided with their usual medical care or their usual medical care supplemented by four virtual visits via video conferencing from a remote specialist. Investigators evaluated the feasibility of telemedicine visits, as measured by the proportion of patients who completed at least one virtual visit and the proportion of virtual visits completed on time. Efficacy was also evaluated, as measured by the change in the Parkinson’s Disease Questionnaire–39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings.

Eligible participants had a clinical diagnosis of Parkinson’s disease, had a private, Internet-enabled device, and lived in a state where a site investigator was licensed to practice. Patients randomized to the telemedicine group received up to four virtual visits over 12 months from a neurologist. Physicians and patients determined the specific content and frequency of each visit, but the format generally included a medical history, a Parkinson’s disease–specific examination (including assessment of tremor and gait), physician recommendations, and time to address patients’ concerns (Neurology. 2017 Aug 16. doi: 10.1212/WNL.0000000000004357).

The study findings showed that the virtual house calls were as effective as were in-person visits, with quality of life no better or worse for patients receiving care at home than for those receiving care in the office. Of telemedicine patients, 98% completed at least one virtual visit, and 91% of all virtual visits scheduled were completed. Researchers also found that participants’ overall quality of care and the burden felt by caregivers was no different whether they had virtual or in-person visits. Each virtual house call saved patients a median of 88 minutes and 38 miles per visit.

Ninety-seven percent of patients and 86% of participating neurologists said they were satisfied with the virtual visits, with 55% of patients stating they preferred virtual visits over in-person visits.

The study – the first national randomized controlled trial of telemedicine to connect remote specialists to patients at home – shows that tele-neurology is a practical and effective model of care for Parkinson patients, said study coauthor E. Ray Dorsey, MD, of the University of Rochester.

“People were very interested in taking part in this study, and the results showed that these virtual house calls were feasible for people with Parkinson’s disease,” Dr. Dorsey said in a statement. “People’s care was as effective as with the in-office visits, and the virtual house calls provided the participants with convenience and comfort.”

Dr. Dorsey noted that 73% of the study participants had visited a Parkinson’s disease specialist in the past year and 83% said they were satisfied with their care, which may have impacted the quality of life finding.

“The fact that adding the virtual house calls to people’s care did not improve their quality of life could be because a large proportion were already seeing a specialist and were satisfied with that care,” he said. “Of course, it’s also possible that virtual house calls are not enough to improve quality of life.”

Limitations of the study included that study participants were primarily well-educated and more familiar with the Internet than was the general population, so results may not be relevant for all people with Parkinson’s disease. In addition, the study population, of whom 96% were white with a mean age of 66 years, did not include people with the disease who live in nursing homes, who account for nearly 25% of all Medicare beneficiaries with Parkinson’s disease.

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Dorsey serves on the medical advisory board of, and has stock options in, Grand Rounds. No other relevant disclosures relevant were reported by study authors.

[email protected]

On Twitter @legal_med

Mutations in SCN1A, SCN2A, and SCN8A, which code for neuronal voltage-gated sodium channel alpha-subunits, have been associated with certain early onset epilepsy syndromes.  Despite this association, many clinicians are uncertain about the value of missense genetic variants in the management of epilepsy because many mutations are classified as having unknown significance. A recent database analysis identified gene variants that are pathogenic and benign, giving clinicians a better understanding of how to interpret SCN test results. Details of the investigation include the following:

• Investigators used 8 algorithms to evaluate the pathogenicity of various genetic variants. They also used logistic regression to help determine if combining algorithms might improve their ability to predict pathogenicity.
• 440 variants were considered pathogenic or likely pathogenic.
• Most computer algorithms that attempt to determine the value of SCN test results are very sensitive but also suffer from low specificity.
• The Mendelian Clinically Applicable Pathogenicity algorithm proved most valuable, with an accuracy of 0.90.

Holland KD, Bouley TM, Horn PS. Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy. Epilepsia. 2017;58(7):1190-1198.

Mutations in SCN1A, SCN2A, and SCN8A, which code for neuronal voltage-gated sodium channel alpha-subunits, have been associated with certain early onset epilepsy syndromes.  Despite this association, many clinicians are uncertain about the value of missense genetic variants in the management of epilepsy because many mutations are classified as having unknown significance. A recent database analysis identified gene variants that are pathogenic and benign, giving clinicians a better understanding of how to interpret SCN test results. Details of the investigation include the following:

• Investigators used 8 algorithms to evaluate the pathogenicity of various genetic variants. They also used logistic regression to help determine if combining algorithms might improve their ability to predict pathogenicity.
• 440 variants were considered pathogenic or likely pathogenic.
• Most computer algorithms that attempt to determine the value of SCN test results are very sensitive but also suffer from low specificity.
• The Mendelian Clinically Applicable Pathogenicity algorithm proved most valuable, with an accuracy of 0.90.

Holland KD, Bouley TM, Horn PS. Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy. Epilepsia. 2017;58(7):1190-1198.

Mutations in SCN1A, SCN2A, and SCN8A, which code for neuronal voltage-gated sodium channel alpha-subunits, have been associated with certain early onset epilepsy syndromes.  Despite this association, many clinicians are uncertain about the value of missense genetic variants in the management of epilepsy because many mutations are classified as having unknown significance. A recent database analysis identified gene variants that are pathogenic and benign, giving clinicians a better understanding of how to interpret SCN test results. Details of the investigation include the following:

• Investigators used 8 algorithms to evaluate the pathogenicity of various genetic variants. They also used logistic regression to help determine if combining algorithms might improve their ability to predict pathogenicity.
• 440 variants were considered pathogenic or likely pathogenic.
• Most computer algorithms that attempt to determine the value of SCN test results are very sensitive but also suffer from low specificity.
• The Mendelian Clinically Applicable Pathogenicity algorithm proved most valuable, with an accuracy of 0.90.

Holland KD, Bouley TM, Horn PS. Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy. Epilepsia. 2017;58(7):1190-1198.

Siblings tend to have a similar response to antiepileptic drugs (AEDs) suggests a study that compared drug response in sibling pairs. Details of the investigation include the following:

• Investigators collected records from a single-center database that included patients with a diagnosis of epilepsy in which their last names, addresses, and parents’ names were matched to determine the existence of siblings with the same disease.
• Twenty-eight sibling pairs were identified, along with 2 sibling trios with epilepsy.
• Seventeen of the sibling pairs had been taking the same initial AED, while 15 pairs had the same type of epilepsy.

• When at least one sibling in a pair improved on an initial AED, the other sibling was more likely to respond if they were taking the same AED compared with those who were taking a different AED.
• While a positive response to an AED predicted success in a sibling taking the same drug, investigators pointed out that their study was retrospective and involved a small sample, which is why they recommended larger prospective trials.

Ueda K, Serajee F, Rajilich J, Taraman S, Steckling L, Huq AM. Sibling response to initial antiepileptic medication predicts treatment success. Epilepsy Res. 2017;136:84-87.

Siblings tend to have a similar response to antiepileptic drugs (AEDs) suggests a study that compared drug response in sibling pairs. Details of the investigation include the following:

• Investigators collected records from a single-center database that included patients with a diagnosis of epilepsy in which their last names, addresses, and parents’ names were matched to determine the existence of siblings with the same disease.
• Twenty-eight sibling pairs were identified, along with 2 sibling trios with epilepsy.
• Seventeen of the sibling pairs had been taking the same initial AED, while 15 pairs had the same type of epilepsy.

• When at least one sibling in a pair improved on an initial AED, the other sibling was more likely to respond if they were taking the same AED compared with those who were taking a different AED.
• While a positive response to an AED predicted success in a sibling taking the same drug, investigators pointed out that their study was retrospective and involved a small sample, which is why they recommended larger prospective trials.

Ueda K, Serajee F, Rajilich J, Taraman S, Steckling L, Huq AM. Sibling response to initial antiepileptic medication predicts treatment success. Epilepsy Res. 2017;136:84-87.

Siblings tend to have a similar response to antiepileptic drugs (AEDs) suggests a study that compared drug response in sibling pairs. Details of the investigation include the following:

• Investigators collected records from a single-center database that included patients with a diagnosis of epilepsy in which their last names, addresses, and parents’ names were matched to determine the existence of siblings with the same disease.
• Twenty-eight sibling pairs were identified, along with 2 sibling trios with epilepsy.
• Seventeen of the sibling pairs had been taking the same initial AED, while 15 pairs had the same type of epilepsy.

• When at least one sibling in a pair improved on an initial AED, the other sibling was more likely to respond if they were taking the same AED compared with those who were taking a different AED.
• While a positive response to an AED predicted success in a sibling taking the same drug, investigators pointed out that their study was retrospective and involved a small sample, which is why they recommended larger prospective trials.

Ueda K, Serajee F, Rajilich J, Taraman S, Steckling L, Huq AM. Sibling response to initial antiepileptic medication predicts treatment success. Epilepsy Res. 2017;136:84-87.

Identifying a seizure propagation network in patients who have undergone surgery for unilateral temporal lobe epilepsy (TLE) may help determine which patients are most likely to remain seizure free over time, according to an analysis of patients who underwent magnetic resonance imaging (MRI) scans. Details of the investigation include the following:

• MRI of 22 unilateral TLE patients found functional connectivity that encompassed the ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula. 35 healthy individuals were included in the study to act as controls.
• Resting state functional and diffusion-weighted 3T magnetic resonance imaging was used in the study.
• The investigators discovered a consistent connectivity pattern representing the network expected in patients who remained seizure free. This was found in 8 patients who did not have seizures one year after surgery.
• Using this model, they were able to differentiate patients with unfavorable outcomes from those with long-term freedom from seizures.

This study provides evidence that network connectivity could be a clinical tool for epilepsy surgery outcome prediction.

Morgan VL, Englot DJ, Rogers BP, et al. Magnetic resonance imaging connectivity for the prediction of seizure outcome in temporal lobe epilepsy. Epilepsia. 2017;58(7):1251-1260.

Identifying a seizure propagation network in patients who have undergone surgery for unilateral temporal lobe epilepsy (TLE) may help determine which patients are most likely to remain seizure free over time, according to an analysis of patients who underwent magnetic resonance imaging (MRI) scans. Details of the investigation include the following:

• MRI of 22 unilateral TLE patients found functional connectivity that encompassed the ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula. 35 healthy individuals were included in the study to act as controls.
• Resting state functional and diffusion-weighted 3T magnetic resonance imaging was used in the study.
• The investigators discovered a consistent connectivity pattern representing the network expected in patients who remained seizure free. This was found in 8 patients who did not have seizures one year after surgery.
• Using this model, they were able to differentiate patients with unfavorable outcomes from those with long-term freedom from seizures.

This study provides evidence that network connectivity could be a clinical tool for epilepsy surgery outcome prediction.

Morgan VL, Englot DJ, Rogers BP, et al. Magnetic resonance imaging connectivity for the prediction of seizure outcome in temporal lobe epilepsy. Epilepsia. 2017;58(7):1251-1260.

Identifying a seizure propagation network in patients who have undergone surgery for unilateral temporal lobe epilepsy (TLE) may help determine which patients are most likely to remain seizure free over time, according to an analysis of patients who underwent magnetic resonance imaging (MRI) scans. Details of the investigation include the following:

• MRI of 22 unilateral TLE patients found functional connectivity that encompassed the ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula. 35 healthy individuals were included in the study to act as controls.
• Resting state functional and diffusion-weighted 3T magnetic resonance imaging was used in the study.
• The investigators discovered a consistent connectivity pattern representing the network expected in patients who remained seizure free. This was found in 8 patients who did not have seizures one year after surgery.
• Using this model, they were able to differentiate patients with unfavorable outcomes from those with long-term freedom from seizures.

This study provides evidence that network connectivity could be a clinical tool for epilepsy surgery outcome prediction.

Morgan VL, Englot DJ, Rogers BP, et al. Magnetic resonance imaging connectivity for the prediction of seizure outcome in temporal lobe epilepsy. Epilepsia. 2017;58(7):1251-1260.

For quite some time now, I’ve been urging my colleagues to follow the science on the powerful impact of choline on the brain.

In May 2017, based on studies using genetically altered mice that show the developmental changes of Down syndrome and Alzheimer’s disease at 6 months, I raised the question of whether prenatal choline could lead to the prevention of Alzheimer’s.

Antonio_Diaz/Thinkstock

*This story was updated August 17, 2017.

For quite some time now, I’ve been urging my colleagues to follow the science on the powerful impact of choline on the brain.

In May 2017, based on studies using genetically altered mice that show the developmental changes of Down syndrome and Alzheimer’s disease at 6 months, I raised the question of whether prenatal choline could lead to the prevention of Alzheimer’s.

Antonio_Diaz/Thinkstock

*This story was updated August 17, 2017.

For quite some time now, I’ve been urging my colleagues to follow the science on the powerful impact of choline on the brain.

In May 2017, based on studies using genetically altered mice that show the developmental changes of Down syndrome and Alzheimer’s disease at 6 months, I raised the question of whether prenatal choline could lead to the prevention of Alzheimer’s.

Antonio_Diaz/Thinkstock

*This story was updated August 17, 2017.