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‘Very daring study’ of neoadjuvant AI/CDKi combo in early BC is hypothesis generating
MADRID – For women with luminal breast cancer who are not initially candidates for breast-conserving surgery, neoadjuvant therapy with an aromatase inhibitor and a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor offered a slightly higher residual cancer burden prior to surgery, but a significantly better safety profile than conventional chemotherapy with similar near-term safety outcomes, results of a phase 2 parallel group, noncomparative trial suggested.
Among 60 patients evaluable for response in an interim analysis of the UNICANCER NeoPAL trial, one patient (3.3%) treated with a combination of letrozole (Femara) and palbociclib (Ibrance) had a residual cancer burden (RCB) score of 0 (equivalent to a pathologic complete response; pCR), whereas three patients (10%) treated with FEC 100 chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide) had RCB 0 or I, reported Paul-Henri Cottu, MD, of the Institut Curie in Paris.
Following the interim analysis, the independent data monitoring committee for the NeoPAL trial recommended halting accrual; accrual was stopped in November 2016, after 106 patients had been randomized.
The IDMC also recommended that patients in the letrozole/palbociclib arm who did not have an RCB of 0 or I be offered adjuvant chemotherapy.
“Please note that 70% of those patients refused adjuvant chemotherapy,” Dr. Cottu said.
The investigators set out to test whether letrozole and palbociclib, which have been shown to have synergistic antiproliferative activity against advanced luminal breast cancer, could have similar benefits in the neoadjuvant setting.
They screened for women with luminal breast cancer who had newly diagnosed stage II or III breast cancer with biopsy-proven endocrine receptor–positive, human epidermal growth factor receptor 2–negative tumors, using the Prosigna test, based on the PAM50 gene signature assay. Women with node-positive luminal A or luminal B disease were enrolled and randomized to receive either letrozole 2.5 mg and palbociclib 125 mg daily for 3 out of every 4 weeks over 19 weeks, or three cycles of FEC 100, followed by three cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery.
An interim analysis was planned after 30 patients were evaluable for RCB in the experimental arm, and, as prespecified, the trial was stopped for futility when fewer than five patients had an RCB of 0 or I.
The safety analysis, conducted with all 106 patients randomized, showed that letrozole/palbocilib was associated with more frequent grade 3 neutropenia (23% vs. 10% of patients with FEC), but less grade 4 neutropenia (1% vs. 11%, respectively), and no febrile neutropenia vs. 6% in the chemotherapy arm.
There were 2 serious adverse events with the AI/CDK-inhibitor combination vs. 17 with chemotherapy. Dose reductions or interruptions were less frequent with letrozole/palbociclib (10 and 16), and only two patients in the experimental arm required premature cessation of therapy vs. seven in the chemotherapy arm.
The final response analysis in 103 patients showed that the rate of RCB 0 or I was 7.7% with letrozole/palbociclib and 15.7% with chemotherapy. Respective rates of RCB II-III were 92.3% and 84.3%.
Clinical response rates were similar in each study arm, with approximately 30% complete responses and 44% partial responses.
In each arm, slightly less than one-third of patients underwent mastectomy, and a little more than two-thirds were able to have breast-conserving surgery after neoadjuvant therapy.
The patients will be followed out to at least 3 years to see whether those patients in the letrozole/palbociclib arm who turned down subsequent chemotherapy will have worse survival than patients who decided to undergo it, Dr. Cottu said.
Invited discussant Nadia Harbeck, MD, PhD, of the University of Munich called the NeoPAL trial “a very daring study.”
“This is not a practice-changing trial, but it’s a very, very interesting hypothesis-generating trial,” she said.
She said that the choice of RCB was probably not the best endpoint in a trial of endocrine-based therapy vs. chemotherapy.
“I think the challenge remains to identify those patients with luminal early breast cancer for whom an endocrine-based approach – not endocrine, but endocrine-based – will improve outcome, either replacing chemotherapy in the intermediate-risk setting or as an add-on in high-risk disease,” she said.
The study was funded by Pfizer and Nanostring. Dr. Cottu disclosed advisory board participation and travel support from Pfizer and others, and research support from Roche, Novartis, and AstraZeneca. Dr. Harbeck disclosed advising and consulting fees from Pfizer, Nanostring, and other companies.
MADRID – For women with luminal breast cancer who are not initially candidates for breast-conserving surgery, neoadjuvant therapy with an aromatase inhibitor and a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor offered a slightly higher residual cancer burden prior to surgery, but a significantly better safety profile than conventional chemotherapy with similar near-term safety outcomes, results of a phase 2 parallel group, noncomparative trial suggested.
Among 60 patients evaluable for response in an interim analysis of the UNICANCER NeoPAL trial, one patient (3.3%) treated with a combination of letrozole (Femara) and palbociclib (Ibrance) had a residual cancer burden (RCB) score of 0 (equivalent to a pathologic complete response; pCR), whereas three patients (10%) treated with FEC 100 chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide) had RCB 0 or I, reported Paul-Henri Cottu, MD, of the Institut Curie in Paris.
Following the interim analysis, the independent data monitoring committee for the NeoPAL trial recommended halting accrual; accrual was stopped in November 2016, after 106 patients had been randomized.
The IDMC also recommended that patients in the letrozole/palbociclib arm who did not have an RCB of 0 or I be offered adjuvant chemotherapy.
“Please note that 70% of those patients refused adjuvant chemotherapy,” Dr. Cottu said.
The investigators set out to test whether letrozole and palbociclib, which have been shown to have synergistic antiproliferative activity against advanced luminal breast cancer, could have similar benefits in the neoadjuvant setting.
They screened for women with luminal breast cancer who had newly diagnosed stage II or III breast cancer with biopsy-proven endocrine receptor–positive, human epidermal growth factor receptor 2–negative tumors, using the Prosigna test, based on the PAM50 gene signature assay. Women with node-positive luminal A or luminal B disease were enrolled and randomized to receive either letrozole 2.5 mg and palbociclib 125 mg daily for 3 out of every 4 weeks over 19 weeks, or three cycles of FEC 100, followed by three cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery.
An interim analysis was planned after 30 patients were evaluable for RCB in the experimental arm, and, as prespecified, the trial was stopped for futility when fewer than five patients had an RCB of 0 or I.
The safety analysis, conducted with all 106 patients randomized, showed that letrozole/palbocilib was associated with more frequent grade 3 neutropenia (23% vs. 10% of patients with FEC), but less grade 4 neutropenia (1% vs. 11%, respectively), and no febrile neutropenia vs. 6% in the chemotherapy arm.
There were 2 serious adverse events with the AI/CDK-inhibitor combination vs. 17 with chemotherapy. Dose reductions or interruptions were less frequent with letrozole/palbociclib (10 and 16), and only two patients in the experimental arm required premature cessation of therapy vs. seven in the chemotherapy arm.
The final response analysis in 103 patients showed that the rate of RCB 0 or I was 7.7% with letrozole/palbociclib and 15.7% with chemotherapy. Respective rates of RCB II-III were 92.3% and 84.3%.
Clinical response rates were similar in each study arm, with approximately 30% complete responses and 44% partial responses.
In each arm, slightly less than one-third of patients underwent mastectomy, and a little more than two-thirds were able to have breast-conserving surgery after neoadjuvant therapy.
The patients will be followed out to at least 3 years to see whether those patients in the letrozole/palbociclib arm who turned down subsequent chemotherapy will have worse survival than patients who decided to undergo it, Dr. Cottu said.
Invited discussant Nadia Harbeck, MD, PhD, of the University of Munich called the NeoPAL trial “a very daring study.”
“This is not a practice-changing trial, but it’s a very, very interesting hypothesis-generating trial,” she said.
She said that the choice of RCB was probably not the best endpoint in a trial of endocrine-based therapy vs. chemotherapy.
“I think the challenge remains to identify those patients with luminal early breast cancer for whom an endocrine-based approach – not endocrine, but endocrine-based – will improve outcome, either replacing chemotherapy in the intermediate-risk setting or as an add-on in high-risk disease,” she said.
The study was funded by Pfizer and Nanostring. Dr. Cottu disclosed advisory board participation and travel support from Pfizer and others, and research support from Roche, Novartis, and AstraZeneca. Dr. Harbeck disclosed advising and consulting fees from Pfizer, Nanostring, and other companies.
MADRID – For women with luminal breast cancer who are not initially candidates for breast-conserving surgery, neoadjuvant therapy with an aromatase inhibitor and a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor offered a slightly higher residual cancer burden prior to surgery, but a significantly better safety profile than conventional chemotherapy with similar near-term safety outcomes, results of a phase 2 parallel group, noncomparative trial suggested.
Among 60 patients evaluable for response in an interim analysis of the UNICANCER NeoPAL trial, one patient (3.3%) treated with a combination of letrozole (Femara) and palbociclib (Ibrance) had a residual cancer burden (RCB) score of 0 (equivalent to a pathologic complete response; pCR), whereas three patients (10%) treated with FEC 100 chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide) had RCB 0 or I, reported Paul-Henri Cottu, MD, of the Institut Curie in Paris.
Following the interim analysis, the independent data monitoring committee for the NeoPAL trial recommended halting accrual; accrual was stopped in November 2016, after 106 patients had been randomized.
The IDMC also recommended that patients in the letrozole/palbociclib arm who did not have an RCB of 0 or I be offered adjuvant chemotherapy.
“Please note that 70% of those patients refused adjuvant chemotherapy,” Dr. Cottu said.
The investigators set out to test whether letrozole and palbociclib, which have been shown to have synergistic antiproliferative activity against advanced luminal breast cancer, could have similar benefits in the neoadjuvant setting.
They screened for women with luminal breast cancer who had newly diagnosed stage II or III breast cancer with biopsy-proven endocrine receptor–positive, human epidermal growth factor receptor 2–negative tumors, using the Prosigna test, based on the PAM50 gene signature assay. Women with node-positive luminal A or luminal B disease were enrolled and randomized to receive either letrozole 2.5 mg and palbociclib 125 mg daily for 3 out of every 4 weeks over 19 weeks, or three cycles of FEC 100, followed by three cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery.
An interim analysis was planned after 30 patients were evaluable for RCB in the experimental arm, and, as prespecified, the trial was stopped for futility when fewer than five patients had an RCB of 0 or I.
The safety analysis, conducted with all 106 patients randomized, showed that letrozole/palbocilib was associated with more frequent grade 3 neutropenia (23% vs. 10% of patients with FEC), but less grade 4 neutropenia (1% vs. 11%, respectively), and no febrile neutropenia vs. 6% in the chemotherapy arm.
There were 2 serious adverse events with the AI/CDK-inhibitor combination vs. 17 with chemotherapy. Dose reductions or interruptions were less frequent with letrozole/palbociclib (10 and 16), and only two patients in the experimental arm required premature cessation of therapy vs. seven in the chemotherapy arm.
The final response analysis in 103 patients showed that the rate of RCB 0 or I was 7.7% with letrozole/palbociclib and 15.7% with chemotherapy. Respective rates of RCB II-III were 92.3% and 84.3%.
Clinical response rates were similar in each study arm, with approximately 30% complete responses and 44% partial responses.
In each arm, slightly less than one-third of patients underwent mastectomy, and a little more than two-thirds were able to have breast-conserving surgery after neoadjuvant therapy.
The patients will be followed out to at least 3 years to see whether those patients in the letrozole/palbociclib arm who turned down subsequent chemotherapy will have worse survival than patients who decided to undergo it, Dr. Cottu said.
Invited discussant Nadia Harbeck, MD, PhD, of the University of Munich called the NeoPAL trial “a very daring study.”
“This is not a practice-changing trial, but it’s a very, very interesting hypothesis-generating trial,” she said.
She said that the choice of RCB was probably not the best endpoint in a trial of endocrine-based therapy vs. chemotherapy.
“I think the challenge remains to identify those patients with luminal early breast cancer for whom an endocrine-based approach – not endocrine, but endocrine-based – will improve outcome, either replacing chemotherapy in the intermediate-risk setting or as an add-on in high-risk disease,” she said.
The study was funded by Pfizer and Nanostring. Dr. Cottu disclosed advisory board participation and travel support from Pfizer and others, and research support from Roche, Novartis, and AstraZeneca. Dr. Harbeck disclosed advising and consulting fees from Pfizer, Nanostring, and other companies.
AT ESMO 2017
Key clinical point:
Major finding: One patient (3.3%) assigned to letrozole/palbociclib had a residual cancer burden score of 0 or I, compared with three patients (10%) assigned to chemotherapy.
Data source: Interim analysis of a phase 2 parallel group trial with 60 patients evaluable for response and 106 evaluable for safety.
Disclosures: The study was funded by Pfizer and Nanostring. Dr. Cottu disclosed advisory board participation and travel support from Pfizer and others and research support from Roche, Novartis, and AstraZeneca. Dr. Harbeck disclosed advising and consulting fees from Pfizer, Nanostring, and other companies.
Picosecond lasers emerging as a go-to for tattoo removal
SAN DIEGO – When counseling patients about laser tattoo removal, resist the temptation to promise clearance in a certain number of treatments.
“You will regret it,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium. “If you say, ‘This looks like this is going to take 6-8 treatments, this looks very simple to me,’ you’ll find that you’ll have someone who requires 15-18 treatments. Further, partial clearing may be cosmetically inferior than nontreatment.”
“These target the microscopic tattoo particles located inside dermal phagocytic cells and scattered extracellularly throughout the dermis,” Dr. Avram explained. The Q-switched laser heats particles to more than 1,000º C within nanoseconds, or billionths of a second. “It produces extreme heat, cavitation, and cell rupture,” he said. “The clinical endpoint is immediate epidermal whitening of tattooed skin.” The process causes transdermal elimination; some of it flows into the lymphatic system, while the rest undergoes rephagocytosis by dermal scavenger cells.
Picosecond lasers are even faster than their Q-switched counterparts, delivering high energies in trillionths of a second. “A picosecond is to a second as 1 second is to 37,000 years,” Dr. Avram said. Commercially available picosecond (ps) lasers include devices with wavelengths of 532 nm, 755 nm, and 1,064 nm that deliver energy in a range of 300-750 ps. The Nd:YAG lasers work best for red and black ink, while Alexandrite lasers work best for green and blue ink.
In Dr. Avram’s experience, ps lasers are generally more effective for tattoo removal, compared with nanosecond lasers. “There’s some nonselective targeting of other pigments, and they’re particularly effective for faded tattoos,” he said. “Combining nanosecond and picosecond devices provides enhanced results, but picosecond lasers are more expensive.”
The clinical endpoint for ps lasers is the same as for nanosecond lasers: epidermal whitening. He said he schedules about 8 weeks between treatments. “If you don’t inform patients of the expectations, they’re going to be very disappointed with you,” Dr. Avram said. “You need to tell them that it’s going to take a lot of treatments and that it may not clear completely. You may be working with them for a year or 2.”
The checklist prior to the first treatment with any laser involves assessing the type of tattoo (amateur or professional), the color of the tattoo, patient skin type, and the duration of the tattoo. “You also want to palpate for an existing scar,” he said. “A lot of times, patients don’t recognize they have a scar on the treatment site. You don’t want to own a complication that has nothing to do with your treatments. Photographing the scar is also important.”
Hyperpigmentation or hypopigmentation is a greater concern in darker skin types or tanned individuals, compared with fairer-skinned patients. “The 1,064-nm Q-switched Nd:YAG laser is the least likely to affect skin pigment,” said Dr. Avram, who is codirector of the Massachusetts General Hospital/Wellman Laser and Cosmetic Fellowship. “It’s safest for Fitzpatrick skin types IV-VI but it’s not very effective for green, blue, and red tattoo ink colors. Some degree of dyspigmentation occurs in most patients regardless of skin type. Much of this is temporary and improves with time, but it may take months to years.”
Professional tattoos are the most difficult to treat because they often feature dense and deeply placed tattoo ink and require 6-20 or more treatments to improve, he said. On the other hand, amateur tattoos, traumatic tattoos, and radiation tattoos improve more rapidly and generally require fewer treatment to yield improvement.
“Color is key,” Dr. Avram said. “If you have different colors in one tattoo, it is going to be more difficult to clear.” Black and dark-blue tattoos respond best to laser, while light blue and green also respond well. Red responds well, but purple can be challenging. “Yellow and orange do not respond well, but they respond partially,” he said.
Researchers who conducted a large cohort trial of variables influencing the outcome of tattoos treated by Q-switched lasers found that 47% of tattoos were cleared after 10 treatment sessions, while 75% were cleared after 15 sessions (Arch Dermatol. 2012;148[12]:1364-9). Predictors of poor response included smoking, the presence of colors other than black and red, tattoo size larger than 30 cm2, location on the feet or legs, duration greater than 36 months, high color density, and treatment intervals of 8 weeks or less.
Dr. Avram cautioned against taking a “cookbook” approach to treating tattoos and underscored the importance of decreasing the fluence if tissue “splatter” occurs, as this may produce scarring. “The treating clinician should follow the treatment endpoint, not the laser fluences,” he said. “Do not use IPL [intense pulsed light therapy] for tattoos; that’s inappropriate and you may end up scarring your patient.”
Common adverse effects include erythema, blistering, hyper- and hypopigmentation, and scarring. Less common adverse effects include an allergic reaction, darkening of the cosmetic tattoo, an immune reaction, and chrysiasis, a dark-blue pigmentation caused by Q-switched laser treatment in patients with a history of gold-salt ingestion. “Any history of gold ingestion will produce this finding, even if they ingested 40 years ago,” he said. “This is very difficult to correct.”
The optimal interval between treatments continues to be explored. For example, the R20 method consists of four treatments separated by 20 minutes. The initial study found that this approach led to better outcomes, compared with conventional, single-pass laser treatment (J Am Acad Dermatol. 2012;66[2]:271-7). A companion technology that is playing a role in such repeat treatments is a Food and Drug Administration–approved transparent silicone patch infused with perfluorodecalin that helps reduce scattering and improves efficacy.
“It also allows for performing consecutive repeat laser treatments at the same visit,” Dr. Avram said. In one study, 11 of 17 patients had more rapid clearance on the side treated with the perfluorodecalin patch, compared with the side that was treated without the patch (Laser Surg Med. 2015;47[8]:613-8).
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea.
[email protected]
SAN DIEGO – When counseling patients about laser tattoo removal, resist the temptation to promise clearance in a certain number of treatments.
“You will regret it,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium. “If you say, ‘This looks like this is going to take 6-8 treatments, this looks very simple to me,’ you’ll find that you’ll have someone who requires 15-18 treatments. Further, partial clearing may be cosmetically inferior than nontreatment.”
“These target the microscopic tattoo particles located inside dermal phagocytic cells and scattered extracellularly throughout the dermis,” Dr. Avram explained. The Q-switched laser heats particles to more than 1,000º C within nanoseconds, or billionths of a second. “It produces extreme heat, cavitation, and cell rupture,” he said. “The clinical endpoint is immediate epidermal whitening of tattooed skin.” The process causes transdermal elimination; some of it flows into the lymphatic system, while the rest undergoes rephagocytosis by dermal scavenger cells.
Picosecond lasers are even faster than their Q-switched counterparts, delivering high energies in trillionths of a second. “A picosecond is to a second as 1 second is to 37,000 years,” Dr. Avram said. Commercially available picosecond (ps) lasers include devices with wavelengths of 532 nm, 755 nm, and 1,064 nm that deliver energy in a range of 300-750 ps. The Nd:YAG lasers work best for red and black ink, while Alexandrite lasers work best for green and blue ink.
In Dr. Avram’s experience, ps lasers are generally more effective for tattoo removal, compared with nanosecond lasers. “There’s some nonselective targeting of other pigments, and they’re particularly effective for faded tattoos,” he said. “Combining nanosecond and picosecond devices provides enhanced results, but picosecond lasers are more expensive.”
The clinical endpoint for ps lasers is the same as for nanosecond lasers: epidermal whitening. He said he schedules about 8 weeks between treatments. “If you don’t inform patients of the expectations, they’re going to be very disappointed with you,” Dr. Avram said. “You need to tell them that it’s going to take a lot of treatments and that it may not clear completely. You may be working with them for a year or 2.”
The checklist prior to the first treatment with any laser involves assessing the type of tattoo (amateur or professional), the color of the tattoo, patient skin type, and the duration of the tattoo. “You also want to palpate for an existing scar,” he said. “A lot of times, patients don’t recognize they have a scar on the treatment site. You don’t want to own a complication that has nothing to do with your treatments. Photographing the scar is also important.”
Hyperpigmentation or hypopigmentation is a greater concern in darker skin types or tanned individuals, compared with fairer-skinned patients. “The 1,064-nm Q-switched Nd:YAG laser is the least likely to affect skin pigment,” said Dr. Avram, who is codirector of the Massachusetts General Hospital/Wellman Laser and Cosmetic Fellowship. “It’s safest for Fitzpatrick skin types IV-VI but it’s not very effective for green, blue, and red tattoo ink colors. Some degree of dyspigmentation occurs in most patients regardless of skin type. Much of this is temporary and improves with time, but it may take months to years.”
Professional tattoos are the most difficult to treat because they often feature dense and deeply placed tattoo ink and require 6-20 or more treatments to improve, he said. On the other hand, amateur tattoos, traumatic tattoos, and radiation tattoos improve more rapidly and generally require fewer treatment to yield improvement.
“Color is key,” Dr. Avram said. “If you have different colors in one tattoo, it is going to be more difficult to clear.” Black and dark-blue tattoos respond best to laser, while light blue and green also respond well. Red responds well, but purple can be challenging. “Yellow and orange do not respond well, but they respond partially,” he said.
Researchers who conducted a large cohort trial of variables influencing the outcome of tattoos treated by Q-switched lasers found that 47% of tattoos were cleared after 10 treatment sessions, while 75% were cleared after 15 sessions (Arch Dermatol. 2012;148[12]:1364-9). Predictors of poor response included smoking, the presence of colors other than black and red, tattoo size larger than 30 cm2, location on the feet or legs, duration greater than 36 months, high color density, and treatment intervals of 8 weeks or less.
Dr. Avram cautioned against taking a “cookbook” approach to treating tattoos and underscored the importance of decreasing the fluence if tissue “splatter” occurs, as this may produce scarring. “The treating clinician should follow the treatment endpoint, not the laser fluences,” he said. “Do not use IPL [intense pulsed light therapy] for tattoos; that’s inappropriate and you may end up scarring your patient.”
Common adverse effects include erythema, blistering, hyper- and hypopigmentation, and scarring. Less common adverse effects include an allergic reaction, darkening of the cosmetic tattoo, an immune reaction, and chrysiasis, a dark-blue pigmentation caused by Q-switched laser treatment in patients with a history of gold-salt ingestion. “Any history of gold ingestion will produce this finding, even if they ingested 40 years ago,” he said. “This is very difficult to correct.”
The optimal interval between treatments continues to be explored. For example, the R20 method consists of four treatments separated by 20 minutes. The initial study found that this approach led to better outcomes, compared with conventional, single-pass laser treatment (J Am Acad Dermatol. 2012;66[2]:271-7). A companion technology that is playing a role in such repeat treatments is a Food and Drug Administration–approved transparent silicone patch infused with perfluorodecalin that helps reduce scattering and improves efficacy.
“It also allows for performing consecutive repeat laser treatments at the same visit,” Dr. Avram said. In one study, 11 of 17 patients had more rapid clearance on the side treated with the perfluorodecalin patch, compared with the side that was treated without the patch (Laser Surg Med. 2015;47[8]:613-8).
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea.
[email protected]
SAN DIEGO – When counseling patients about laser tattoo removal, resist the temptation to promise clearance in a certain number of treatments.
“You will regret it,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium. “If you say, ‘This looks like this is going to take 6-8 treatments, this looks very simple to me,’ you’ll find that you’ll have someone who requires 15-18 treatments. Further, partial clearing may be cosmetically inferior than nontreatment.”
“These target the microscopic tattoo particles located inside dermal phagocytic cells and scattered extracellularly throughout the dermis,” Dr. Avram explained. The Q-switched laser heats particles to more than 1,000º C within nanoseconds, or billionths of a second. “It produces extreme heat, cavitation, and cell rupture,” he said. “The clinical endpoint is immediate epidermal whitening of tattooed skin.” The process causes transdermal elimination; some of it flows into the lymphatic system, while the rest undergoes rephagocytosis by dermal scavenger cells.
Picosecond lasers are even faster than their Q-switched counterparts, delivering high energies in trillionths of a second. “A picosecond is to a second as 1 second is to 37,000 years,” Dr. Avram said. Commercially available picosecond (ps) lasers include devices with wavelengths of 532 nm, 755 nm, and 1,064 nm that deliver energy in a range of 300-750 ps. The Nd:YAG lasers work best for red and black ink, while Alexandrite lasers work best for green and blue ink.
In Dr. Avram’s experience, ps lasers are generally more effective for tattoo removal, compared with nanosecond lasers. “There’s some nonselective targeting of other pigments, and they’re particularly effective for faded tattoos,” he said. “Combining nanosecond and picosecond devices provides enhanced results, but picosecond lasers are more expensive.”
The clinical endpoint for ps lasers is the same as for nanosecond lasers: epidermal whitening. He said he schedules about 8 weeks between treatments. “If you don’t inform patients of the expectations, they’re going to be very disappointed with you,” Dr. Avram said. “You need to tell them that it’s going to take a lot of treatments and that it may not clear completely. You may be working with them for a year or 2.”
The checklist prior to the first treatment with any laser involves assessing the type of tattoo (amateur or professional), the color of the tattoo, patient skin type, and the duration of the tattoo. “You also want to palpate for an existing scar,” he said. “A lot of times, patients don’t recognize they have a scar on the treatment site. You don’t want to own a complication that has nothing to do with your treatments. Photographing the scar is also important.”
Hyperpigmentation or hypopigmentation is a greater concern in darker skin types or tanned individuals, compared with fairer-skinned patients. “The 1,064-nm Q-switched Nd:YAG laser is the least likely to affect skin pigment,” said Dr. Avram, who is codirector of the Massachusetts General Hospital/Wellman Laser and Cosmetic Fellowship. “It’s safest for Fitzpatrick skin types IV-VI but it’s not very effective for green, blue, and red tattoo ink colors. Some degree of dyspigmentation occurs in most patients regardless of skin type. Much of this is temporary and improves with time, but it may take months to years.”
Professional tattoos are the most difficult to treat because they often feature dense and deeply placed tattoo ink and require 6-20 or more treatments to improve, he said. On the other hand, amateur tattoos, traumatic tattoos, and radiation tattoos improve more rapidly and generally require fewer treatment to yield improvement.
“Color is key,” Dr. Avram said. “If you have different colors in one tattoo, it is going to be more difficult to clear.” Black and dark-blue tattoos respond best to laser, while light blue and green also respond well. Red responds well, but purple can be challenging. “Yellow and orange do not respond well, but they respond partially,” he said.
Researchers who conducted a large cohort trial of variables influencing the outcome of tattoos treated by Q-switched lasers found that 47% of tattoos were cleared after 10 treatment sessions, while 75% were cleared after 15 sessions (Arch Dermatol. 2012;148[12]:1364-9). Predictors of poor response included smoking, the presence of colors other than black and red, tattoo size larger than 30 cm2, location on the feet or legs, duration greater than 36 months, high color density, and treatment intervals of 8 weeks or less.
Dr. Avram cautioned against taking a “cookbook” approach to treating tattoos and underscored the importance of decreasing the fluence if tissue “splatter” occurs, as this may produce scarring. “The treating clinician should follow the treatment endpoint, not the laser fluences,” he said. “Do not use IPL [intense pulsed light therapy] for tattoos; that’s inappropriate and you may end up scarring your patient.”
Common adverse effects include erythema, blistering, hyper- and hypopigmentation, and scarring. Less common adverse effects include an allergic reaction, darkening of the cosmetic tattoo, an immune reaction, and chrysiasis, a dark-blue pigmentation caused by Q-switched laser treatment in patients with a history of gold-salt ingestion. “Any history of gold ingestion will produce this finding, even if they ingested 40 years ago,” he said. “This is very difficult to correct.”
The optimal interval between treatments continues to be explored. For example, the R20 method consists of four treatments separated by 20 minutes. The initial study found that this approach led to better outcomes, compared with conventional, single-pass laser treatment (J Am Acad Dermatol. 2012;66[2]:271-7). A companion technology that is playing a role in such repeat treatments is a Food and Drug Administration–approved transparent silicone patch infused with perfluorodecalin that helps reduce scattering and improves efficacy.
“It also allows for performing consecutive repeat laser treatments at the same visit,” Dr. Avram said. In one study, 11 of 17 patients had more rapid clearance on the side treated with the perfluorodecalin patch, compared with the side that was treated without the patch (Laser Surg Med. 2015;47[8]:613-8).
Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea.
[email protected]
AT MOAS 2017
RAS derangement linked to CVD risk in adolescents born preterm
SAN FRANCISCO – The renin-angiotensin system (RAS) is out of balance in adolescents born prematurely, according to investigators from Wake Forest School of Medicine in Winston-Salem, N.C.
Among other findings, the amount of circulating angiotensin 1-7, a vasodilator that counteracts the vasoconstrictive and other effects of angiotensin II, was lower relative to angiotensin II in 175 subjects born preterm and assessed at age 14 years, compared with 51 controls born at term.
The findings suggest a possible explanation for why people born prematurely have an increased risk for hypertension and cardiovascular disease, which has been a mystery. If the findings pan out with additional research, they also suggest potential therapeutic targets to attenuate the risk, namely upregulating angiotensin 1-7 and blocking angiotensin II, either at birth or later.
“If you could give medications to shift the balance in the RAS back to what it should be, then maybe you could prevent some of the changes that we see at age 14. With the current treatments, that’s difficult; ACE inhibitors and angiotensin II receptor blockers are (generally) not used in the neonatal period because they can precipitate acute kidney injury.” For older patients, “there’s no indication to use these medications in a subtle situation like we have here,” Dr. South said in an interview at a hypertension science meeting jointly sponsored by the American Heart Association and the American Society of Hypertension.
The direct manipulation of angiotensin 1-7 remains, for now, largely in the realm of clinical research.
The preterm subjects had lower plasma angiotensin II and lower angiotensin 1-7 concentrations, compared with their term peers, but an overall increase in the angiotensin II/angiotensin 1-7 ratio (4.2 vs. 2.4). Preterm subjects also had increased urinary excretion of angiotensin 1-7. The findings were statistically significant, and adjusted for potential confounders.
The differences were exaggerated in obese subjects, about a third in both groups. Obesity is known to be associated with increased angiotensin II activity.
The drop in angiotensin 1-7 was greater in preterm girls than in boys, which was curious because female sex is normally associated with decreased angiotensin II activity, and estrogen normally upregulates angiotensin 1-7; perhaps in prematurity, there’s a breakdown in the normal response to estrogen, Dr. South said.
Whatever the case, it’s possible the risk of hypertension and cardiovascular disease from preterm birth might be especially high in obese patients and women, he said.
The preterm group had a mean gestational age of 28 weeks, and a mean birth weight of 1.1 kg. The term group was born at a mean of 40 weeks, with a mean birth weight of 3.5 kg. At age 14 years, preterm subjects were shorter and weighed less than their peers.
Mean systolic and diastolic blood pressures were higher in the preterm group, and 21 preterm subjects (12%) had blood pressures at or above 120/80 mm Hg, vs. one subject (2%) in the term group.
Maternal hypertension and smoking during pregnancy, and C-section delivery, were far more common in the preterm group, as was Medicaid use at age 14 years. There were slightly more girls than boys in both groups, and just over 40% of the subjects in each were black.
The Wake Forest team continues to follow their preterm subjects, who are now in their mid-twenties. “If we can correlate what we found at age 14 with” early development of disease, “it will give us more of an indication that this is actually true causation, not just an association,” Dr. South said.
The investigators had no industry disclosures. The work was funded in part by the National Institutes of Health.
[email protected]
SAN FRANCISCO – The renin-angiotensin system (RAS) is out of balance in adolescents born prematurely, according to investigators from Wake Forest School of Medicine in Winston-Salem, N.C.
Among other findings, the amount of circulating angiotensin 1-7, a vasodilator that counteracts the vasoconstrictive and other effects of angiotensin II, was lower relative to angiotensin II in 175 subjects born preterm and assessed at age 14 years, compared with 51 controls born at term.
The findings suggest a possible explanation for why people born prematurely have an increased risk for hypertension and cardiovascular disease, which has been a mystery. If the findings pan out with additional research, they also suggest potential therapeutic targets to attenuate the risk, namely upregulating angiotensin 1-7 and blocking angiotensin II, either at birth or later.
“If you could give medications to shift the balance in the RAS back to what it should be, then maybe you could prevent some of the changes that we see at age 14. With the current treatments, that’s difficult; ACE inhibitors and angiotensin II receptor blockers are (generally) not used in the neonatal period because they can precipitate acute kidney injury.” For older patients, “there’s no indication to use these medications in a subtle situation like we have here,” Dr. South said in an interview at a hypertension science meeting jointly sponsored by the American Heart Association and the American Society of Hypertension.
The direct manipulation of angiotensin 1-7 remains, for now, largely in the realm of clinical research.
The preterm subjects had lower plasma angiotensin II and lower angiotensin 1-7 concentrations, compared with their term peers, but an overall increase in the angiotensin II/angiotensin 1-7 ratio (4.2 vs. 2.4). Preterm subjects also had increased urinary excretion of angiotensin 1-7. The findings were statistically significant, and adjusted for potential confounders.
The differences were exaggerated in obese subjects, about a third in both groups. Obesity is known to be associated with increased angiotensin II activity.
The drop in angiotensin 1-7 was greater in preterm girls than in boys, which was curious because female sex is normally associated with decreased angiotensin II activity, and estrogen normally upregulates angiotensin 1-7; perhaps in prematurity, there’s a breakdown in the normal response to estrogen, Dr. South said.
Whatever the case, it’s possible the risk of hypertension and cardiovascular disease from preterm birth might be especially high in obese patients and women, he said.
The preterm group had a mean gestational age of 28 weeks, and a mean birth weight of 1.1 kg. The term group was born at a mean of 40 weeks, with a mean birth weight of 3.5 kg. At age 14 years, preterm subjects were shorter and weighed less than their peers.
Mean systolic and diastolic blood pressures were higher in the preterm group, and 21 preterm subjects (12%) had blood pressures at or above 120/80 mm Hg, vs. one subject (2%) in the term group.
Maternal hypertension and smoking during pregnancy, and C-section delivery, were far more common in the preterm group, as was Medicaid use at age 14 years. There were slightly more girls than boys in both groups, and just over 40% of the subjects in each were black.
The Wake Forest team continues to follow their preterm subjects, who are now in their mid-twenties. “If we can correlate what we found at age 14 with” early development of disease, “it will give us more of an indication that this is actually true causation, not just an association,” Dr. South said.
The investigators had no industry disclosures. The work was funded in part by the National Institutes of Health.
[email protected]
SAN FRANCISCO – The renin-angiotensin system (RAS) is out of balance in adolescents born prematurely, according to investigators from Wake Forest School of Medicine in Winston-Salem, N.C.
Among other findings, the amount of circulating angiotensin 1-7, a vasodilator that counteracts the vasoconstrictive and other effects of angiotensin II, was lower relative to angiotensin II in 175 subjects born preterm and assessed at age 14 years, compared with 51 controls born at term.
The findings suggest a possible explanation for why people born prematurely have an increased risk for hypertension and cardiovascular disease, which has been a mystery. If the findings pan out with additional research, they also suggest potential therapeutic targets to attenuate the risk, namely upregulating angiotensin 1-7 and blocking angiotensin II, either at birth or later.
“If you could give medications to shift the balance in the RAS back to what it should be, then maybe you could prevent some of the changes that we see at age 14. With the current treatments, that’s difficult; ACE inhibitors and angiotensin II receptor blockers are (generally) not used in the neonatal period because they can precipitate acute kidney injury.” For older patients, “there’s no indication to use these medications in a subtle situation like we have here,” Dr. South said in an interview at a hypertension science meeting jointly sponsored by the American Heart Association and the American Society of Hypertension.
The direct manipulation of angiotensin 1-7 remains, for now, largely in the realm of clinical research.
The preterm subjects had lower plasma angiotensin II and lower angiotensin 1-7 concentrations, compared with their term peers, but an overall increase in the angiotensin II/angiotensin 1-7 ratio (4.2 vs. 2.4). Preterm subjects also had increased urinary excretion of angiotensin 1-7. The findings were statistically significant, and adjusted for potential confounders.
The differences were exaggerated in obese subjects, about a third in both groups. Obesity is known to be associated with increased angiotensin II activity.
The drop in angiotensin 1-7 was greater in preterm girls than in boys, which was curious because female sex is normally associated with decreased angiotensin II activity, and estrogen normally upregulates angiotensin 1-7; perhaps in prematurity, there’s a breakdown in the normal response to estrogen, Dr. South said.
Whatever the case, it’s possible the risk of hypertension and cardiovascular disease from preterm birth might be especially high in obese patients and women, he said.
The preterm group had a mean gestational age of 28 weeks, and a mean birth weight of 1.1 kg. The term group was born at a mean of 40 weeks, with a mean birth weight of 3.5 kg. At age 14 years, preterm subjects were shorter and weighed less than their peers.
Mean systolic and diastolic blood pressures were higher in the preterm group, and 21 preterm subjects (12%) had blood pressures at or above 120/80 mm Hg, vs. one subject (2%) in the term group.
Maternal hypertension and smoking during pregnancy, and C-section delivery, were far more common in the preterm group, as was Medicaid use at age 14 years. There were slightly more girls than boys in both groups, and just over 40% of the subjects in each were black.
The Wake Forest team continues to follow their preterm subjects, who are now in their mid-twenties. “If we can correlate what we found at age 14 with” early development of disease, “it will give us more of an indication that this is actually true causation, not just an association,” Dr. South said.
The investigators had no industry disclosures. The work was funded in part by the National Institutes of Health.
[email protected]
AT THE AHA/ASH JOINT SCIENTIFIC HYPERTENSION MEETING
Key clinical point:
Major finding: The preterm subjects had lower plasma angiotensin II and lower angiotensin 1-7 concentrations, compared with their term peers, but an overall increase in the angiotensin II/angiotensin 1-7 ratio (4.2 vs. 2.4).
Data source: Comparison of 175 subjects born preterm to 51 controls born at term, assessed at age 14 years.
Disclosures: The investigators had no industry disclosures. The work was funded in part by the National Institutes of Health.
Alternative therapies
Alternative therapies, from vitamins and supplements to meditation and acupuncture, have become increasingly popular treatments in the United States for many medical problems in the past few decades. In 2008, the National Institutes of Health reported that nearly 40% of adults and 12% of children had used “complementary or alternative medicine” (CAM) in the preceding year. Other surveys have suggested that closer to 30% of general pediatric patients and as many as 75% of adolescent patients have used CAM at least once. These treatments are especially popular for chronic conditions that are managed but not usually cured with current evidence-based treatments. Psychiatric conditions in childhood sometimes have a long course, and have effective but controversial treatments, as with stimulants for ADHD. Parents sometimes feel guilty about their child’s problem and want to use “natural” methods or deny the accepted understanding of their child’s illness. So it is not surprising that families may investigate alternative treatments, and such treatments have multiplied.
While there is evidence that parents and patients rarely discuss these treatments with their physicians, it is critical that you know what therapies your patients are using. You should focus on tolerance in the context of protecting the child from harm and improving the child’s functioning. If you have ever recommended chicken soup for a cold, then you have prescribed complementary medicine, so it is not a stretch for you to offer some input about the other alternative therapies your patients may be considering.
It is important to note that rigorous, case-controlled studies of efficacy of most alternative therapies are few in number and usually small in size (so any evidence of efficacy is weaker), and that the products themselves are not regulated by the Food and Drug Administration or other public body. This means that the family (and you) will have to do some homework to ensure that the therapy they purchase comes from a reputable source and is what it purports to be.
Many of the alternative therapies patients are investigating will be herbs or supplements. Omega-3 fatty acids are critical to multiple essential body functions, and are taken in primarily via certain foods, primarily fish and certain seeds and nuts. A deficiency in certain omega-3 fatty acids can cause problems in infant neurological development and put one at risk for heart disease, rheumatologic illness, and depression. Supplementation with Omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA], specifically) has a solid evidence base as an effective adjunctive treatment for depression and bipolar disorder in adults. In addition, randomized, placebo-controlled, double-blind studies have demonstrated efficacy in treatment of children with mild to moderate ADHD at doses of 1,200 mg/day. There are some studies that have demonstrated improvement in hyperactivity in children with autism with supplementation at similar doses. These supplements have very low risk of side effects. They are a reasonable recommendation to your patients whose children have mild to moderate ADHD, and they want to manage it without stimulants.
Families also may be considering physical or mechanical treatments. Acupuncture has demonstrated efficacy in the treatment of fatigue and pain, migraines, and addiction, although there are very few studies in children and adolescents. There is some evidence for its efficacy in treatment of mild to moderate depression and anxiety in adults, but again no research has been done in youth. Hypnotherapy has shown modest efficacy in treatment of anticipatory anxiety symptoms, headache, chronic pain, nausea and vomiting, migraines, hair-pulling and skin picking as well as compulsive eating and smoking cessation in adults. There is some clinical evidence for its efficacy in children and adolescents, and its safety is well established. Massage therapy has shown value in improving mood and behavior in children with ADHD, but not efficacy as a first-line treatment for ADHD symptoms. Chiropractic care, which is among the most commonly used alternative therapies, claims to be effective for the treatment of anxiety, depression, ADHD, behavioral problems of autism and even schizophrenia and bipolar disorder, but there is no significant scientific evidence to support these claims. And neurofeedback, which is a variant of biofeedback in which patients practice calming themselves or improving focus while watching an EEG has shown modest efficacy in the treatment of ADHD in children in early studies. It is worth noting that all of these therapies may be costly and not covered by insurance.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Additional readings
1. Child Adolesc Psychiatr Clin N Am. 2013 Jul;22(3):375-80.
2. J Am Acad Child Adolesc Psychiatry. 2008;47(4):364-8.
3. J Am Acad Child Adolesc Psychiatry. 2011;50(10):991-1000.
4. J Am Acad Child Adolesc Psychiatry. 2014 Jun; 53(6):658-66.
5. J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):S168-9.
Alternative therapies, from vitamins and supplements to meditation and acupuncture, have become increasingly popular treatments in the United States for many medical problems in the past few decades. In 2008, the National Institutes of Health reported that nearly 40% of adults and 12% of children had used “complementary or alternative medicine” (CAM) in the preceding year. Other surveys have suggested that closer to 30% of general pediatric patients and as many as 75% of adolescent patients have used CAM at least once. These treatments are especially popular for chronic conditions that are managed but not usually cured with current evidence-based treatments. Psychiatric conditions in childhood sometimes have a long course, and have effective but controversial treatments, as with stimulants for ADHD. Parents sometimes feel guilty about their child’s problem and want to use “natural” methods or deny the accepted understanding of their child’s illness. So it is not surprising that families may investigate alternative treatments, and such treatments have multiplied.
While there is evidence that parents and patients rarely discuss these treatments with their physicians, it is critical that you know what therapies your patients are using. You should focus on tolerance in the context of protecting the child from harm and improving the child’s functioning. If you have ever recommended chicken soup for a cold, then you have prescribed complementary medicine, so it is not a stretch for you to offer some input about the other alternative therapies your patients may be considering.
It is important to note that rigorous, case-controlled studies of efficacy of most alternative therapies are few in number and usually small in size (so any evidence of efficacy is weaker), and that the products themselves are not regulated by the Food and Drug Administration or other public body. This means that the family (and you) will have to do some homework to ensure that the therapy they purchase comes from a reputable source and is what it purports to be.
Many of the alternative therapies patients are investigating will be herbs or supplements. Omega-3 fatty acids are critical to multiple essential body functions, and are taken in primarily via certain foods, primarily fish and certain seeds and nuts. A deficiency in certain omega-3 fatty acids can cause problems in infant neurological development and put one at risk for heart disease, rheumatologic illness, and depression. Supplementation with Omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA], specifically) has a solid evidence base as an effective adjunctive treatment for depression and bipolar disorder in adults. In addition, randomized, placebo-controlled, double-blind studies have demonstrated efficacy in treatment of children with mild to moderate ADHD at doses of 1,200 mg/day. There are some studies that have demonstrated improvement in hyperactivity in children with autism with supplementation at similar doses. These supplements have very low risk of side effects. They are a reasonable recommendation to your patients whose children have mild to moderate ADHD, and they want to manage it without stimulants.
Families also may be considering physical or mechanical treatments. Acupuncture has demonstrated efficacy in the treatment of fatigue and pain, migraines, and addiction, although there are very few studies in children and adolescents. There is some evidence for its efficacy in treatment of mild to moderate depression and anxiety in adults, but again no research has been done in youth. Hypnotherapy has shown modest efficacy in treatment of anticipatory anxiety symptoms, headache, chronic pain, nausea and vomiting, migraines, hair-pulling and skin picking as well as compulsive eating and smoking cessation in adults. There is some clinical evidence for its efficacy in children and adolescents, and its safety is well established. Massage therapy has shown value in improving mood and behavior in children with ADHD, but not efficacy as a first-line treatment for ADHD symptoms. Chiropractic care, which is among the most commonly used alternative therapies, claims to be effective for the treatment of anxiety, depression, ADHD, behavioral problems of autism and even schizophrenia and bipolar disorder, but there is no significant scientific evidence to support these claims. And neurofeedback, which is a variant of biofeedback in which patients practice calming themselves or improving focus while watching an EEG has shown modest efficacy in the treatment of ADHD in children in early studies. It is worth noting that all of these therapies may be costly and not covered by insurance.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Additional readings
1. Child Adolesc Psychiatr Clin N Am. 2013 Jul;22(3):375-80.
2. J Am Acad Child Adolesc Psychiatry. 2008;47(4):364-8.
3. J Am Acad Child Adolesc Psychiatry. 2011;50(10):991-1000.
4. J Am Acad Child Adolesc Psychiatry. 2014 Jun; 53(6):658-66.
5. J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):S168-9.
Alternative therapies, from vitamins and supplements to meditation and acupuncture, have become increasingly popular treatments in the United States for many medical problems in the past few decades. In 2008, the National Institutes of Health reported that nearly 40% of adults and 12% of children had used “complementary or alternative medicine” (CAM) in the preceding year. Other surveys have suggested that closer to 30% of general pediatric patients and as many as 75% of adolescent patients have used CAM at least once. These treatments are especially popular for chronic conditions that are managed but not usually cured with current evidence-based treatments. Psychiatric conditions in childhood sometimes have a long course, and have effective but controversial treatments, as with stimulants for ADHD. Parents sometimes feel guilty about their child’s problem and want to use “natural” methods or deny the accepted understanding of their child’s illness. So it is not surprising that families may investigate alternative treatments, and such treatments have multiplied.
While there is evidence that parents and patients rarely discuss these treatments with their physicians, it is critical that you know what therapies your patients are using. You should focus on tolerance in the context of protecting the child from harm and improving the child’s functioning. If you have ever recommended chicken soup for a cold, then you have prescribed complementary medicine, so it is not a stretch for you to offer some input about the other alternative therapies your patients may be considering.
It is important to note that rigorous, case-controlled studies of efficacy of most alternative therapies are few in number and usually small in size (so any evidence of efficacy is weaker), and that the products themselves are not regulated by the Food and Drug Administration or other public body. This means that the family (and you) will have to do some homework to ensure that the therapy they purchase comes from a reputable source and is what it purports to be.
Many of the alternative therapies patients are investigating will be herbs or supplements. Omega-3 fatty acids are critical to multiple essential body functions, and are taken in primarily via certain foods, primarily fish and certain seeds and nuts. A deficiency in certain omega-3 fatty acids can cause problems in infant neurological development and put one at risk for heart disease, rheumatologic illness, and depression. Supplementation with Omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA], specifically) has a solid evidence base as an effective adjunctive treatment for depression and bipolar disorder in adults. In addition, randomized, placebo-controlled, double-blind studies have demonstrated efficacy in treatment of children with mild to moderate ADHD at doses of 1,200 mg/day. There are some studies that have demonstrated improvement in hyperactivity in children with autism with supplementation at similar doses. These supplements have very low risk of side effects. They are a reasonable recommendation to your patients whose children have mild to moderate ADHD, and they want to manage it without stimulants.
Families also may be considering physical or mechanical treatments. Acupuncture has demonstrated efficacy in the treatment of fatigue and pain, migraines, and addiction, although there are very few studies in children and adolescents. There is some evidence for its efficacy in treatment of mild to moderate depression and anxiety in adults, but again no research has been done in youth. Hypnotherapy has shown modest efficacy in treatment of anticipatory anxiety symptoms, headache, chronic pain, nausea and vomiting, migraines, hair-pulling and skin picking as well as compulsive eating and smoking cessation in adults. There is some clinical evidence for its efficacy in children and adolescents, and its safety is well established. Massage therapy has shown value in improving mood and behavior in children with ADHD, but not efficacy as a first-line treatment for ADHD symptoms. Chiropractic care, which is among the most commonly used alternative therapies, claims to be effective for the treatment of anxiety, depression, ADHD, behavioral problems of autism and even schizophrenia and bipolar disorder, but there is no significant scientific evidence to support these claims. And neurofeedback, which is a variant of biofeedback in which patients practice calming themselves or improving focus while watching an EEG has shown modest efficacy in the treatment of ADHD in children in early studies. It is worth noting that all of these therapies may be costly and not covered by insurance.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
Additional readings
1. Child Adolesc Psychiatr Clin N Am. 2013 Jul;22(3):375-80.
2. J Am Acad Child Adolesc Psychiatry. 2008;47(4):364-8.
3. J Am Acad Child Adolesc Psychiatry. 2011;50(10):991-1000.
4. J Am Acad Child Adolesc Psychiatry. 2014 Jun; 53(6):658-66.
5. J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):S168-9.
Lessons abound for dermatologists when animal health and human health intersect
NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.
That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.
“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.
Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.
The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.
Learning from the mighty mite
For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.
Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.
In such cases, “sulfur tends to be my most reliable” treatment, he said, noting that it releases a rotten egg smell. “You’re basically gassing the organism.” Dr. Elston said he frequently gets calls from fellow dermatologists whose antimite efforts have failed with ivermectin and permethrin and does not hesitate to give his advice. “I’m like a broken record,” he said. “Sulfur, sulfur, sulfur, sulfur.”
The Demodex mite affects dogs to varying degrees, depending on where they live, said Kathryn Rook, VMD, of the department of dermatology at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. In North America, demodicosis occurs in 0.38%-0.58% of dogs, and in 25% of dogs in Mexico, she said.
Amitraz, the only Food and Drug Administration–approved treatment for canine demodicosis, is available only as a dip. But it has fallen from favor as a result of sometimes serious side effects, which can include sedation, bradycardia, ataxia, vomiting, diarrhea, and hyperglycemia.
Daily administration of oral ivermectin – often for months – also carries a risk of side effects, including dilated pupils, ataxia, sedation, stupor, coma, hypersalivation, vomiting, diarrhea, blindness, tremors, seizures, and respiratory depression.
But the discovery of isoxazoline has “revolutionized” the treatment of demodicosis and other parasitic infestations in dogs, Dr. Rook said, citing quicker resolution of disease and improved quality of life for both the patient and its owner.
Isoxazoline, which Dr. Rook said carries little risk for side effects, is licensed in the United States only as a flea and tick preventive.
Atopic dermatitis
Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.
In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.
In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.
“My true love is anything to do with the skin microbiome,” she said. “The more severe the disease, the lower the skin microbiome diversity.”
Though most studies of AD use mice as animal models, dogs would be better, according to Dr. Grice and Dr. Bradley.
That’s because canine AD occurs spontaneously and exhibits immunologic and clinical features similar to those of human AD. They include prevalence, environmental triggers, immunologic profiles, genetic predispositions, lesion distribution, and frequent colonization by Staphylococcus species. In addition, dogs and their owners tend to share the same environment.
A rash of itches
Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.
For dogs, advances have been made with Janus kinase (JAK) inhibitors, which “may function as immunomodulators,” Dr. Kim said. And JAK-1 selective inhibition “may be more effective than broad JAK blockade for itch.”
‘The perfect culture plate’
Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.
Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”
But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.
A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.
Monoclonal antibody targets IL-31
The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.
But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.
Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.
Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.
NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.
That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.
“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.
Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.
The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.
Learning from the mighty mite
For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.
Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.
In such cases, “sulfur tends to be my most reliable” treatment, he said, noting that it releases a rotten egg smell. “You’re basically gassing the organism.” Dr. Elston said he frequently gets calls from fellow dermatologists whose antimite efforts have failed with ivermectin and permethrin and does not hesitate to give his advice. “I’m like a broken record,” he said. “Sulfur, sulfur, sulfur, sulfur.”
The Demodex mite affects dogs to varying degrees, depending on where they live, said Kathryn Rook, VMD, of the department of dermatology at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. In North America, demodicosis occurs in 0.38%-0.58% of dogs, and in 25% of dogs in Mexico, she said.
Amitraz, the only Food and Drug Administration–approved treatment for canine demodicosis, is available only as a dip. But it has fallen from favor as a result of sometimes serious side effects, which can include sedation, bradycardia, ataxia, vomiting, diarrhea, and hyperglycemia.
Daily administration of oral ivermectin – often for months – also carries a risk of side effects, including dilated pupils, ataxia, sedation, stupor, coma, hypersalivation, vomiting, diarrhea, blindness, tremors, seizures, and respiratory depression.
But the discovery of isoxazoline has “revolutionized” the treatment of demodicosis and other parasitic infestations in dogs, Dr. Rook said, citing quicker resolution of disease and improved quality of life for both the patient and its owner.
Isoxazoline, which Dr. Rook said carries little risk for side effects, is licensed in the United States only as a flea and tick preventive.
Atopic dermatitis
Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.
In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.
In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.
“My true love is anything to do with the skin microbiome,” she said. “The more severe the disease, the lower the skin microbiome diversity.”
Though most studies of AD use mice as animal models, dogs would be better, according to Dr. Grice and Dr. Bradley.
That’s because canine AD occurs spontaneously and exhibits immunologic and clinical features similar to those of human AD. They include prevalence, environmental triggers, immunologic profiles, genetic predispositions, lesion distribution, and frequent colonization by Staphylococcus species. In addition, dogs and their owners tend to share the same environment.
A rash of itches
Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.
For dogs, advances have been made with Janus kinase (JAK) inhibitors, which “may function as immunomodulators,” Dr. Kim said. And JAK-1 selective inhibition “may be more effective than broad JAK blockade for itch.”
‘The perfect culture plate’
Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.
Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”
But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.
A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.
Monoclonal antibody targets IL-31
The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.
But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.
Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.
Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.
NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.
That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.
“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.
Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.
The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.
Learning from the mighty mite
For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.
Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.
In such cases, “sulfur tends to be my most reliable” treatment, he said, noting that it releases a rotten egg smell. “You’re basically gassing the organism.” Dr. Elston said he frequently gets calls from fellow dermatologists whose antimite efforts have failed with ivermectin and permethrin and does not hesitate to give his advice. “I’m like a broken record,” he said. “Sulfur, sulfur, sulfur, sulfur.”
The Demodex mite affects dogs to varying degrees, depending on where they live, said Kathryn Rook, VMD, of the department of dermatology at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. In North America, demodicosis occurs in 0.38%-0.58% of dogs, and in 25% of dogs in Mexico, she said.
Amitraz, the only Food and Drug Administration–approved treatment for canine demodicosis, is available only as a dip. But it has fallen from favor as a result of sometimes serious side effects, which can include sedation, bradycardia, ataxia, vomiting, diarrhea, and hyperglycemia.
Daily administration of oral ivermectin – often for months – also carries a risk of side effects, including dilated pupils, ataxia, sedation, stupor, coma, hypersalivation, vomiting, diarrhea, blindness, tremors, seizures, and respiratory depression.
But the discovery of isoxazoline has “revolutionized” the treatment of demodicosis and other parasitic infestations in dogs, Dr. Rook said, citing quicker resolution of disease and improved quality of life for both the patient and its owner.
Isoxazoline, which Dr. Rook said carries little risk for side effects, is licensed in the United States only as a flea and tick preventive.
Atopic dermatitis
Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.
In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.
In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.
“My true love is anything to do with the skin microbiome,” she said. “The more severe the disease, the lower the skin microbiome diversity.”
Though most studies of AD use mice as animal models, dogs would be better, according to Dr. Grice and Dr. Bradley.
That’s because canine AD occurs spontaneously and exhibits immunologic and clinical features similar to those of human AD. They include prevalence, environmental triggers, immunologic profiles, genetic predispositions, lesion distribution, and frequent colonization by Staphylococcus species. In addition, dogs and their owners tend to share the same environment.
A rash of itches
Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.
For dogs, advances have been made with Janus kinase (JAK) inhibitors, which “may function as immunomodulators,” Dr. Kim said. And JAK-1 selective inhibition “may be more effective than broad JAK blockade for itch.”
‘The perfect culture plate’
Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.
Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”
But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.
A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.
Monoclonal antibody targets IL-31
The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.
But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.
Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.
Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.
AT THE 2017 AAD SUMMER MEETING
Lomitapide manufacturer will plead guilty to two misdemeanor charges of misbranding
Juxtapid was misbranded because Aegerion failed to comply with the requirements of the Juxtapid Risk Evaluation and Mitigation Strategy (REMS) program and because the drug’s labeling lacked adequate directions for all of Juxtapid’s intended uses, according to the charges. Aegerion also agreed to a comprehensive compliance program and legal tools for the FDA to ensure that Aegerion complies with the law, subject to judicial oversight.
Rather than following the REMS requirement to distribute Juxtapid only for the narrow indication of homozygous familial hypercholesterolemia, Aegerion portrayed the definition of the rare disorder as vague and indefinite in order to extend its use to lower-risk patients. Further, Aegerion filed a misleading REMS assessment report to the FDA in which the company failed to disclose that it was distributing Juxtapid using this definition, which was inconsistent with Aegerion’s preapproval filings and peer-reviewed clinical standards of diagnosis, according to the FDA release.
Once entered by the court, the plea and consent decree will be part of a global resolution of multiple government investigations into Aegerion’s conduct with respect to the marketing and distribution of Juxtapid. This resolution was the result of a coordinated effort by the U.S. Department of Justice and several government agencies, including the FDA, the press release stated.
Juxtapid was approved in December 2012 as an adjunct therapy to treat homozygous familial hypercholesterolemia. The Juxtapid REMS requires Aegerion to educate prescribers about the risks of hepatotoxicity and the need to monitor patients treated with Juxtapid and to ensure that Juxtapid is prescribed and dispensed only to those patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia.
Juxtapid was misbranded because Aegerion failed to comply with the requirements of the Juxtapid Risk Evaluation and Mitigation Strategy (REMS) program and because the drug’s labeling lacked adequate directions for all of Juxtapid’s intended uses, according to the charges. Aegerion also agreed to a comprehensive compliance program and legal tools for the FDA to ensure that Aegerion complies with the law, subject to judicial oversight.
Rather than following the REMS requirement to distribute Juxtapid only for the narrow indication of homozygous familial hypercholesterolemia, Aegerion portrayed the definition of the rare disorder as vague and indefinite in order to extend its use to lower-risk patients. Further, Aegerion filed a misleading REMS assessment report to the FDA in which the company failed to disclose that it was distributing Juxtapid using this definition, which was inconsistent with Aegerion’s preapproval filings and peer-reviewed clinical standards of diagnosis, according to the FDA release.
Once entered by the court, the plea and consent decree will be part of a global resolution of multiple government investigations into Aegerion’s conduct with respect to the marketing and distribution of Juxtapid. This resolution was the result of a coordinated effort by the U.S. Department of Justice and several government agencies, including the FDA, the press release stated.
Juxtapid was approved in December 2012 as an adjunct therapy to treat homozygous familial hypercholesterolemia. The Juxtapid REMS requires Aegerion to educate prescribers about the risks of hepatotoxicity and the need to monitor patients treated with Juxtapid and to ensure that Juxtapid is prescribed and dispensed only to those patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia.
Juxtapid was misbranded because Aegerion failed to comply with the requirements of the Juxtapid Risk Evaluation and Mitigation Strategy (REMS) program and because the drug’s labeling lacked adequate directions for all of Juxtapid’s intended uses, according to the charges. Aegerion also agreed to a comprehensive compliance program and legal tools for the FDA to ensure that Aegerion complies with the law, subject to judicial oversight.
Rather than following the REMS requirement to distribute Juxtapid only for the narrow indication of homozygous familial hypercholesterolemia, Aegerion portrayed the definition of the rare disorder as vague and indefinite in order to extend its use to lower-risk patients. Further, Aegerion filed a misleading REMS assessment report to the FDA in which the company failed to disclose that it was distributing Juxtapid using this definition, which was inconsistent with Aegerion’s preapproval filings and peer-reviewed clinical standards of diagnosis, according to the FDA release.
Once entered by the court, the plea and consent decree will be part of a global resolution of multiple government investigations into Aegerion’s conduct with respect to the marketing and distribution of Juxtapid. This resolution was the result of a coordinated effort by the U.S. Department of Justice and several government agencies, including the FDA, the press release stated.
Juxtapid was approved in December 2012 as an adjunct therapy to treat homozygous familial hypercholesterolemia. The Juxtapid REMS requires Aegerion to educate prescribers about the risks of hepatotoxicity and the need to monitor patients treated with Juxtapid and to ensure that Juxtapid is prescribed and dispensed only to those patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia.
EC expands approval of obinutuzumab in FL
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%). 
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
Swiss freedom, hidden witnesses, and beer
Most of medical practice is mundane. Just a few interesting cases pass through now and then to break up the clinical routine, a rhythm that’s fine with me.
More often, patients expand my vistas by telling me about places I’ve never been and things I didn’t know and couldn’t imagine. Sometimes these tales are even more riveting than atopic dermatitis or mildly dysplastic nevi. Learning about them leaves me smiling and scratching my head. What will they tell me about next?
“I always come to Boston around this time,” she said. “But today I actually am celebrating Swiss National Day.”
“No kidding,” I said. “What is Swiss National Day?”
“We commemorate the founding of Switzerland in 1291,” she said.
“And how do you celebrate it?” I asked.
“Well, we are Swiss,” she said, “so we work all day. Then we have a party in the evening.
“That is how it used to be anyway,” she said. “About 40 years ago, the parties on the left and right made a deal and established two holidays: Labor Day on May 1st and the National Holiday on August 1st. Now we get those whole days off.”
“Which was the end of Swiss civilization as we know it,” I suggested.
“That’s exactly what my father said when it happened,” said Valentina, with a restrained, Swiss smile. “But somehow life goes on for us, even with 2 days a year off.”
* * * * * * * * * * * * * * * * * * * * * * *
When I picked up his chart, I saw that my patient’s last name suggested that he hailed from one of the countries left after the breakup of Yugoslavia. We’ll call him Magovcevic.
As soon as I walked in, however, it was clear that wherever he came from was nowhere near Serbia. His features and accent were Brazilian.
“I come from Minas Gerais,” he said, “in the South, not far from Rio.”
“So how come you have a Slavic name?” I asked him.
“My parents had a different last name,” he said.
“Then how did you come to be called Magovcevic?” I asked.
“I’m in the witness protection program,” he said.
I had to hold onto the sink to stay upright. Of all the possible responses he could have made, that one was not on my list.
“Did you pick the name yourself?” I asked. I don’t think I’d ever given a thought to how family names are chosen for people in witness protection.
“No, they gave it to me,” he said. “I was still a minor.”
At that point I stopped asking questions. Whatever it was that he witnessed as a minor that landed him in witness protection I didn’t want to know about.
* * * * * * * * * * * * * * * * * * * * * * *
Myrna was very happy to tell me that her son was doing well in college and had a good summer job.
“He works in a beer garden downtown,” she said. “The tips are great.”
“What is he studying in school?” I asked.
“Fermentation studies,” she replied.
After she’d said he was moonlighting in a beer garden, I thought she was pulling my leg. I know college students have keg parties after class, but I didn’t know they studied what goes into the kegs during class.
But Myrna was serious. “He’s interested in biochemistry,” she explained. “He wants to focus on developing better beers.”
A younger colleague whom I told about this chuckled at my perplexity. “Sure,” she said, “fermentation studies is the hot new field. Lots of people are getting into it.”
I have long since resigned myself to being clueless about what younger people are into, especially social media. But I found myself bemused at how it just never occurred to me that bright young biochemists might burn with ambition to bring the world better craft beers.
I have since learned that fermentation studies have other applications too. Like wine. And wine, like cosmetics, has been around a lot longer than dermatology.
* * * * * * * * * * * * * * * * * * * * * * *
Skin is interesting, but the people inside it are often even more so. Who knows what I’ll run into tomorrow? I won’t even try to guess.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com.
Most of medical practice is mundane. Just a few interesting cases pass through now and then to break up the clinical routine, a rhythm that’s fine with me.
More often, patients expand my vistas by telling me about places I’ve never been and things I didn’t know and couldn’t imagine. Sometimes these tales are even more riveting than atopic dermatitis or mildly dysplastic nevi. Learning about them leaves me smiling and scratching my head. What will they tell me about next?
“I always come to Boston around this time,” she said. “But today I actually am celebrating Swiss National Day.”
“No kidding,” I said. “What is Swiss National Day?”
“We commemorate the founding of Switzerland in 1291,” she said.
“And how do you celebrate it?” I asked.
“Well, we are Swiss,” she said, “so we work all day. Then we have a party in the evening.
“That is how it used to be anyway,” she said. “About 40 years ago, the parties on the left and right made a deal and established two holidays: Labor Day on May 1st and the National Holiday on August 1st. Now we get those whole days off.”
“Which was the end of Swiss civilization as we know it,” I suggested.
“That’s exactly what my father said when it happened,” said Valentina, with a restrained, Swiss smile. “But somehow life goes on for us, even with 2 days a year off.”
* * * * * * * * * * * * * * * * * * * * * * *
When I picked up his chart, I saw that my patient’s last name suggested that he hailed from one of the countries left after the breakup of Yugoslavia. We’ll call him Magovcevic.
As soon as I walked in, however, it was clear that wherever he came from was nowhere near Serbia. His features and accent were Brazilian.
“I come from Minas Gerais,” he said, “in the South, not far from Rio.”
“So how come you have a Slavic name?” I asked him.
“My parents had a different last name,” he said.
“Then how did you come to be called Magovcevic?” I asked.
“I’m in the witness protection program,” he said.
I had to hold onto the sink to stay upright. Of all the possible responses he could have made, that one was not on my list.
“Did you pick the name yourself?” I asked. I don’t think I’d ever given a thought to how family names are chosen for people in witness protection.
“No, they gave it to me,” he said. “I was still a minor.”
At that point I stopped asking questions. Whatever it was that he witnessed as a minor that landed him in witness protection I didn’t want to know about.
* * * * * * * * * * * * * * * * * * * * * * *
Myrna was very happy to tell me that her son was doing well in college and had a good summer job.
“He works in a beer garden downtown,” she said. “The tips are great.”
“What is he studying in school?” I asked.
“Fermentation studies,” she replied.
After she’d said he was moonlighting in a beer garden, I thought she was pulling my leg. I know college students have keg parties after class, but I didn’t know they studied what goes into the kegs during class.
But Myrna was serious. “He’s interested in biochemistry,” she explained. “He wants to focus on developing better beers.”
A younger colleague whom I told about this chuckled at my perplexity. “Sure,” she said, “fermentation studies is the hot new field. Lots of people are getting into it.”
I have long since resigned myself to being clueless about what younger people are into, especially social media. But I found myself bemused at how it just never occurred to me that bright young biochemists might burn with ambition to bring the world better craft beers.
I have since learned that fermentation studies have other applications too. Like wine. And wine, like cosmetics, has been around a lot longer than dermatology.
* * * * * * * * * * * * * * * * * * * * * * *
Skin is interesting, but the people inside it are often even more so. Who knows what I’ll run into tomorrow? I won’t even try to guess.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com.
Most of medical practice is mundane. Just a few interesting cases pass through now and then to break up the clinical routine, a rhythm that’s fine with me.
More often, patients expand my vistas by telling me about places I’ve never been and things I didn’t know and couldn’t imagine. Sometimes these tales are even more riveting than atopic dermatitis or mildly dysplastic nevi. Learning about them leaves me smiling and scratching my head. What will they tell me about next?
“I always come to Boston around this time,” she said. “But today I actually am celebrating Swiss National Day.”
“No kidding,” I said. “What is Swiss National Day?”
“We commemorate the founding of Switzerland in 1291,” she said.
“And how do you celebrate it?” I asked.
“Well, we are Swiss,” she said, “so we work all day. Then we have a party in the evening.
“That is how it used to be anyway,” she said. “About 40 years ago, the parties on the left and right made a deal and established two holidays: Labor Day on May 1st and the National Holiday on August 1st. Now we get those whole days off.”
“Which was the end of Swiss civilization as we know it,” I suggested.
“That’s exactly what my father said when it happened,” said Valentina, with a restrained, Swiss smile. “But somehow life goes on for us, even with 2 days a year off.”
* * * * * * * * * * * * * * * * * * * * * * *
When I picked up his chart, I saw that my patient’s last name suggested that he hailed from one of the countries left after the breakup of Yugoslavia. We’ll call him Magovcevic.
As soon as I walked in, however, it was clear that wherever he came from was nowhere near Serbia. His features and accent were Brazilian.
“I come from Minas Gerais,” he said, “in the South, not far from Rio.”
“So how come you have a Slavic name?” I asked him.
“My parents had a different last name,” he said.
“Then how did you come to be called Magovcevic?” I asked.
“I’m in the witness protection program,” he said.
I had to hold onto the sink to stay upright. Of all the possible responses he could have made, that one was not on my list.
“Did you pick the name yourself?” I asked. I don’t think I’d ever given a thought to how family names are chosen for people in witness protection.
“No, they gave it to me,” he said. “I was still a minor.”
At that point I stopped asking questions. Whatever it was that he witnessed as a minor that landed him in witness protection I didn’t want to know about.
* * * * * * * * * * * * * * * * * * * * * * *
Myrna was very happy to tell me that her son was doing well in college and had a good summer job.
“He works in a beer garden downtown,” she said. “The tips are great.”
“What is he studying in school?” I asked.
“Fermentation studies,” she replied.
After she’d said he was moonlighting in a beer garden, I thought she was pulling my leg. I know college students have keg parties after class, but I didn’t know they studied what goes into the kegs during class.
But Myrna was serious. “He’s interested in biochemistry,” she explained. “He wants to focus on developing better beers.”
A younger colleague whom I told about this chuckled at my perplexity. “Sure,” she said, “fermentation studies is the hot new field. Lots of people are getting into it.”
I have long since resigned myself to being clueless about what younger people are into, especially social media. But I found myself bemused at how it just never occurred to me that bright young biochemists might burn with ambition to bring the world better craft beers.
I have since learned that fermentation studies have other applications too. Like wine. And wine, like cosmetics, has been around a lot longer than dermatology.
* * * * * * * * * * * * * * * * * * * * * * *
Skin is interesting, but the people inside it are often even more so. Who knows what I’ll run into tomorrow? I won’t even try to guess.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com.
Platelet-rich plasma treatment for hair loss continues to be refined
SAN DIEGO – There is currently no standard protocol for injecting autologous platelet-rich plasma to stimulate hair growth, but the technique appears to be about 50% effective, according to Marc R. Avram, MD.
“I tell patients that this is not FDA [Food and Drug Administration] approved, but we think it to be safe,” said Dr. Avram, clinical professor of dermatology at the Cornell University, New York, said at the annual Masters of Aesthetics Symposium. “We don’t know how well it’s going to work. There are a lot of published data on it, but none of [them are] randomized or controlled long-term.”
In Dr. Avram’s experience, he has found that PRP is a good option for patients with difficult hair loss, such as those who had extensive hair loss after chemotherapy but the hair never grew back in the same fashion, or patients who have failed treatment with finasteride and minoxidil.
Currently, there is no standard protocol for using PRP to stimulate hair growth, but the approach Dr. Avram follows is modeled on his experience of injecting thousands of patients with triamcinolone acetonide (Kenalog) for hair loss every 4-6 weeks. After drawing 20 ccs-30 ccs of blood from the patient, the vial is placed in a centrifuge for 10 minutes, a process that separates PRP from red blood cells. Next, the clinician injects PRP into the deep dermis/superficial subcutaneous tissue of the desired treatment area. An average of 4 ccs-8 ccs is injected during each session.
After three monthly treatments, patients follow up at 3 and 6 months after the last treatment to evaluate efficacy. “All patients are told if there is regrowth or thickening of terminal hair, maintenance treatments will be needed every 6-9 months,” he said.
Published clinical trials of PRP include a follow-up period of 3-12 months and most demonstrate an efficacy in the range of 50%-70%. “It seems to be more effective for earlier stages of hair loss, and there are no known side effects to date,” said Dr. Avram, who has authored five textbooks on hair and cosmetic dermatology. “I had one patient call up to say he thought he had an increase in hair loss 2-3 weeks after treatment, but that’s one patient in a couple hundred. This may be similar to the effect minoxidil has on some patients. I’ve had no other issues with side effects.”
In his opinion, future challenges in the use of PRP for restoring hair loss include better defining optimal candidates for the procedure and establishing a better treatment protocol. “How often should maintenance be done?” he asked. “Is this going to be helpful for alopecia areata and scarring alopecia? Also, we need to determine if finasteride, minoxidil, low-level light laser therapy, or any other medications can enhance PRP efficacy in combination. What’s the optimal combination for patients? We don’t know yet. But I think in the future we will.”
Dr. Avram disclosed that he is a consultant for Restoration Robotics.
SAN DIEGO – There is currently no standard protocol for injecting autologous platelet-rich plasma to stimulate hair growth, but the technique appears to be about 50% effective, according to Marc R. Avram, MD.
“I tell patients that this is not FDA [Food and Drug Administration] approved, but we think it to be safe,” said Dr. Avram, clinical professor of dermatology at the Cornell University, New York, said at the annual Masters of Aesthetics Symposium. “We don’t know how well it’s going to work. There are a lot of published data on it, but none of [them are] randomized or controlled long-term.”
In Dr. Avram’s experience, he has found that PRP is a good option for patients with difficult hair loss, such as those who had extensive hair loss after chemotherapy but the hair never grew back in the same fashion, or patients who have failed treatment with finasteride and minoxidil.
Currently, there is no standard protocol for using PRP to stimulate hair growth, but the approach Dr. Avram follows is modeled on his experience of injecting thousands of patients with triamcinolone acetonide (Kenalog) for hair loss every 4-6 weeks. After drawing 20 ccs-30 ccs of blood from the patient, the vial is placed in a centrifuge for 10 minutes, a process that separates PRP from red blood cells. Next, the clinician injects PRP into the deep dermis/superficial subcutaneous tissue of the desired treatment area. An average of 4 ccs-8 ccs is injected during each session.
After three monthly treatments, patients follow up at 3 and 6 months after the last treatment to evaluate efficacy. “All patients are told if there is regrowth or thickening of terminal hair, maintenance treatments will be needed every 6-9 months,” he said.
Published clinical trials of PRP include a follow-up period of 3-12 months and most demonstrate an efficacy in the range of 50%-70%. “It seems to be more effective for earlier stages of hair loss, and there are no known side effects to date,” said Dr. Avram, who has authored five textbooks on hair and cosmetic dermatology. “I had one patient call up to say he thought he had an increase in hair loss 2-3 weeks after treatment, but that’s one patient in a couple hundred. This may be similar to the effect minoxidil has on some patients. I’ve had no other issues with side effects.”
In his opinion, future challenges in the use of PRP for restoring hair loss include better defining optimal candidates for the procedure and establishing a better treatment protocol. “How often should maintenance be done?” he asked. “Is this going to be helpful for alopecia areata and scarring alopecia? Also, we need to determine if finasteride, minoxidil, low-level light laser therapy, or any other medications can enhance PRP efficacy in combination. What’s the optimal combination for patients? We don’t know yet. But I think in the future we will.”
Dr. Avram disclosed that he is a consultant for Restoration Robotics.
SAN DIEGO – There is currently no standard protocol for injecting autologous platelet-rich plasma to stimulate hair growth, but the technique appears to be about 50% effective, according to Marc R. Avram, MD.
“I tell patients that this is not FDA [Food and Drug Administration] approved, but we think it to be safe,” said Dr. Avram, clinical professor of dermatology at the Cornell University, New York, said at the annual Masters of Aesthetics Symposium. “We don’t know how well it’s going to work. There are a lot of published data on it, but none of [them are] randomized or controlled long-term.”
In Dr. Avram’s experience, he has found that PRP is a good option for patients with difficult hair loss, such as those who had extensive hair loss after chemotherapy but the hair never grew back in the same fashion, or patients who have failed treatment with finasteride and minoxidil.
Currently, there is no standard protocol for using PRP to stimulate hair growth, but the approach Dr. Avram follows is modeled on his experience of injecting thousands of patients with triamcinolone acetonide (Kenalog) for hair loss every 4-6 weeks. After drawing 20 ccs-30 ccs of blood from the patient, the vial is placed in a centrifuge for 10 minutes, a process that separates PRP from red blood cells. Next, the clinician injects PRP into the deep dermis/superficial subcutaneous tissue of the desired treatment area. An average of 4 ccs-8 ccs is injected during each session.
After three monthly treatments, patients follow up at 3 and 6 months after the last treatment to evaluate efficacy. “All patients are told if there is regrowth or thickening of terminal hair, maintenance treatments will be needed every 6-9 months,” he said.
Published clinical trials of PRP include a follow-up period of 3-12 months and most demonstrate an efficacy in the range of 50%-70%. “It seems to be more effective for earlier stages of hair loss, and there are no known side effects to date,” said Dr. Avram, who has authored five textbooks on hair and cosmetic dermatology. “I had one patient call up to say he thought he had an increase in hair loss 2-3 weeks after treatment, but that’s one patient in a couple hundred. This may be similar to the effect minoxidil has on some patients. I’ve had no other issues with side effects.”
In his opinion, future challenges in the use of PRP for restoring hair loss include better defining optimal candidates for the procedure and establishing a better treatment protocol. “How often should maintenance be done?” he asked. “Is this going to be helpful for alopecia areata and scarring alopecia? Also, we need to determine if finasteride, minoxidil, low-level light laser therapy, or any other medications can enhance PRP efficacy in combination. What’s the optimal combination for patients? We don’t know yet. But I think in the future we will.”
Dr. Avram disclosed that he is a consultant for Restoration Robotics.
AT MOAS 2017
Sharing drug paraphernalia alone didn’t transmit HCV
nevertheless, according to researchers at Yale University, New Haven, Conn.
That makes sharing paraphernalia a “surrogate” for HCV transmission “resulting from sharing drugs,” the investigators said, but it should not be a primary focus of harm-reduction and education programs.
“Water was introduced into the barrel of a contaminated ‘input’ syringe and expelled into a ‘cooker,’ and the water was drawn up into a ‘receptive’ syringe through a cotton filter,” the study authors explained. “The ‘input’ syringe, ‘cooker,’ and filter were rinsed with tissue culture medium and introduced into the microculture assay. The water drawn into the second syringe was combined with an equal volume of double-strength medium and introduced into the microculture assay” (J Infect Dis. 2017. doi: 10.1093/infdis/jix427).
The researchers tested syringes (with fixed or detachable needles), cookers, and filters (single or pooled). They were significantly more likely to recover HCV from detachable-needle syringes than from fixed-needle syringes. In the input syringes, they recovered no HCV from 70 fixed-needle syringes while they did recover HCV from 96 of 130 (73.8%) detachable-needle syringes. HCV passed to both types of syringes in the experiment’s receptive syringes but at a much higher rate for those with detachable needles than for those with fixed needles (93.8% vs. 45.7%, respectively).
No HCV was recovered from any of the cookers, regardless of syringe type. Some was recovered from filters, at higher rates with detachable needles than with fixed (27.1% vs. 1.4%).
“Money spent on ‘cookers’ and filters would be better spent on giving away more syringes,” Dr. Heimer and his coauthors concluded. “Because HCV and HIV transmission are more likely if the syringe has a detachable rather than a fixed needle, efforts should focus on providing more syringes with fixed needles.”
nevertheless, according to researchers at Yale University, New Haven, Conn.
That makes sharing paraphernalia a “surrogate” for HCV transmission “resulting from sharing drugs,” the investigators said, but it should not be a primary focus of harm-reduction and education programs.
“Water was introduced into the barrel of a contaminated ‘input’ syringe and expelled into a ‘cooker,’ and the water was drawn up into a ‘receptive’ syringe through a cotton filter,” the study authors explained. “The ‘input’ syringe, ‘cooker,’ and filter were rinsed with tissue culture medium and introduced into the microculture assay. The water drawn into the second syringe was combined with an equal volume of double-strength medium and introduced into the microculture assay” (J Infect Dis. 2017. doi: 10.1093/infdis/jix427).
The researchers tested syringes (with fixed or detachable needles), cookers, and filters (single or pooled). They were significantly more likely to recover HCV from detachable-needle syringes than from fixed-needle syringes. In the input syringes, they recovered no HCV from 70 fixed-needle syringes while they did recover HCV from 96 of 130 (73.8%) detachable-needle syringes. HCV passed to both types of syringes in the experiment’s receptive syringes but at a much higher rate for those with detachable needles than for those with fixed needles (93.8% vs. 45.7%, respectively).
No HCV was recovered from any of the cookers, regardless of syringe type. Some was recovered from filters, at higher rates with detachable needles than with fixed (27.1% vs. 1.4%).
“Money spent on ‘cookers’ and filters would be better spent on giving away more syringes,” Dr. Heimer and his coauthors concluded. “Because HCV and HIV transmission are more likely if the syringe has a detachable rather than a fixed needle, efforts should focus on providing more syringes with fixed needles.”
nevertheless, according to researchers at Yale University, New Haven, Conn.
That makes sharing paraphernalia a “surrogate” for HCV transmission “resulting from sharing drugs,” the investigators said, but it should not be a primary focus of harm-reduction and education programs.
“Water was introduced into the barrel of a contaminated ‘input’ syringe and expelled into a ‘cooker,’ and the water was drawn up into a ‘receptive’ syringe through a cotton filter,” the study authors explained. “The ‘input’ syringe, ‘cooker,’ and filter were rinsed with tissue culture medium and introduced into the microculture assay. The water drawn into the second syringe was combined with an equal volume of double-strength medium and introduced into the microculture assay” (J Infect Dis. 2017. doi: 10.1093/infdis/jix427).
The researchers tested syringes (with fixed or detachable needles), cookers, and filters (single or pooled). They were significantly more likely to recover HCV from detachable-needle syringes than from fixed-needle syringes. In the input syringes, they recovered no HCV from 70 fixed-needle syringes while they did recover HCV from 96 of 130 (73.8%) detachable-needle syringes. HCV passed to both types of syringes in the experiment’s receptive syringes but at a much higher rate for those with detachable needles than for those with fixed needles (93.8% vs. 45.7%, respectively).
No HCV was recovered from any of the cookers, regardless of syringe type. Some was recovered from filters, at higher rates with detachable needles than with fixed (27.1% vs. 1.4%).
“Money spent on ‘cookers’ and filters would be better spent on giving away more syringes,” Dr. Heimer and his coauthors concluded. “Because HCV and HIV transmission are more likely if the syringe has a detachable rather than a fixed needle, efforts should focus on providing more syringes with fixed needles.”
FROM THE JOURNAL OF INFECTIOUS DISEASES