ORLANDO – The first time a man walks in for an aesthetic consultation, he probably doesn’t know what to expect, according to Terrence Keaney, MD, a dermatologist in private practice in Arlington, Va. And he may not even be sure what he’s looking for.

However, he probably knows what he doesn’t like about his appearance. When men are questioned, the three areas they are most concerned about is their hairline, their eyes, and their jawline, said Dr. Keaney, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.

It’s important to evaluate men differently, not just for anatomic differences from women, but also for behavioral and psychological factors unique to men as aesthetic patients, he noted.

Anatomic differences are significant and fundamentally shape treatment decisions, Dr. Keaney said. Broadly speaking, “the male face is traditionally more square, with a prominent supraorbital ridge.” Rather than emphasizing breadth across the cheeks, as in rejuvenation for women, a strong, youthful male face will have a square jaw, appropriate width across the cheeks, and a strong brow line with an arch that is flatter than what women seek.

Male cosmetic goals can be complicated by the fact that men “age poorly” and tend to look older than their stated age, he continued, referring to a study that found that men appear about one-third year older than their age, and women about a half year younger. A higher rate of smoking and excess ultraviolet light exposure among men may contribute to this discrepancy, he said.

Overall, men see steady atrophy of facial soft tissue throughout adulthood, in contrast to women who see a more rapid decline that starts at menopause. This makes sense in the context of the slow drop in circulating testosterone that men see beginning at about age 30, at which time men can expect a decrease of about 1% per year, he noted.

A common opener from men, said Dr. Keaney, is “’I look tired.’ When I hear that, I’m thinking about the eyes.” Men are more likely to develop tear troughs and a sunken appearance because of their larger orbital cavities and smaller orbital fat pads, so periocular fillers are often a treatment tool to consider.

Around mens’ eyes, “it’s not just the presence, but the pattern of wrinkles that guides treatment,” he noted. At the lateral canthi, both at rest and with maximum smile, the predominant wrinkle pattern in crows’ feet is the lower fan. The cheek elevator musculature, including the zygomaticus major, are more involved in animation around the eyes with smiling, which is important because reaching for botulinum toxin alone is probably not going to give the patient his desired effect, he added.

Other differences in the male wrinkle pattern can be found on the brow. The “U” contraction pattern between the brows is more common in men than women, at least partly because men have greater involvement of the procerus muscle, Dr. Keaney said.

Taking all of this into account, caution is the watchword when using botulinum toxin for the glabellar and brow region. “Beware of eyebrow ptosis: avoid the frontalis in patients with eyebrow ptosis,” he said. Treating the corrugators can also be an unwise move, since toxin can diffuse to the inferior fibers of the frontalis muscle, he added.

For men with jawline concerns, consider a combination approach, Dr. Keaney said. The lower face and neck can be rejuvenated by a redraping solution, such as skin tightening with high frequency ultrasound or radiofrequency ablation.

Sometimes, a clean, tight sweep of jawline can be restored with dermal fillers to the lower face, along with a noninvasive fat reduction approach, said Dr. Keaney.

Knowing men’s unique anatomy and aging patterns is only half the battle, though. “How you communicate with men and evaluate them has to take into account that you might be seeing a sweaty, nervous, treatment-naive patient,” at the initial consultation, said Dr. Keaney. “Do men care? Yes, but men display a different set of motivations.”

Plan for all of this to take time. “The initial consultation tends to be longer” for male patients, who are “less savvy” about cosmetic procedures than women, he pointed out.

A clear discussion of side effects is critical when discussing treatment options with men. “If they get a side effect, you’ll never see them again – and you won’t ever hear about it,” he added.

Though overall, women have been shown to be more sensitive to pain, in cosmetic procedures, “men are less tolerant of pain.” Plan for this, set reasonable expectations but be proactive about pain control, and still expect a need for some hand-holding, said Dr. Keaney.

“Men do not like surprises,” he added. Clearly define what expected side effects may be, what they’ll look like, and what downtime the patient should expect.

For Dr. Keaney’s part, he’s found that the best way to retain men in his cosmetic practice is to “start with a home run treatment to earn trust.” Men often appreciate a slow and steady approach to addressing concerns. “Make sure to connect the treatment plan to the primary cosmetic concern.”

Dr. Keaney reported that he has relationships with multiple pharmaceutical and cosmetic companies.

koakes@mdedge.com

ORLANDO – The first time a man walks in for an aesthetic consultation, he probably doesn’t know what to expect, according to Terrence Keaney, MD, a dermatologist in private practice in Arlington, Va. And he may not even be sure what he’s looking for.

However, he probably knows what he doesn’t like about his appearance. When men are questioned, the three areas they are most concerned about is their hairline, their eyes, and their jawline, said Dr. Keaney, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.

It’s important to evaluate men differently, not just for anatomic differences from women, but also for behavioral and psychological factors unique to men as aesthetic patients, he noted.

Anatomic differences are significant and fundamentally shape treatment decisions, Dr. Keaney said. Broadly speaking, “the male face is traditionally more square, with a prominent supraorbital ridge.” Rather than emphasizing breadth across the cheeks, as in rejuvenation for women, a strong, youthful male face will have a square jaw, appropriate width across the cheeks, and a strong brow line with an arch that is flatter than what women seek.

Male cosmetic goals can be complicated by the fact that men “age poorly” and tend to look older than their stated age, he continued, referring to a study that found that men appear about one-third year older than their age, and women about a half year younger. A higher rate of smoking and excess ultraviolet light exposure among men may contribute to this discrepancy, he said.

Overall, men see steady atrophy of facial soft tissue throughout adulthood, in contrast to women who see a more rapid decline that starts at menopause. This makes sense in the context of the slow drop in circulating testosterone that men see beginning at about age 30, at which time men can expect a decrease of about 1% per year, he noted.

A common opener from men, said Dr. Keaney, is “’I look tired.’ When I hear that, I’m thinking about the eyes.” Men are more likely to develop tear troughs and a sunken appearance because of their larger orbital cavities and smaller orbital fat pads, so periocular fillers are often a treatment tool to consider.

Around mens’ eyes, “it’s not just the presence, but the pattern of wrinkles that guides treatment,” he noted. At the lateral canthi, both at rest and with maximum smile, the predominant wrinkle pattern in crows’ feet is the lower fan. The cheek elevator musculature, including the zygomaticus major, are more involved in animation around the eyes with smiling, which is important because reaching for botulinum toxin alone is probably not going to give the patient his desired effect, he added.

Other differences in the male wrinkle pattern can be found on the brow. The “U” contraction pattern between the brows is more common in men than women, at least partly because men have greater involvement of the procerus muscle, Dr. Keaney said.

Taking all of this into account, caution is the watchword when using botulinum toxin for the glabellar and brow region. “Beware of eyebrow ptosis: avoid the frontalis in patients with eyebrow ptosis,” he said. Treating the corrugators can also be an unwise move, since toxin can diffuse to the inferior fibers of the frontalis muscle, he added.

For men with jawline concerns, consider a combination approach, Dr. Keaney said. The lower face and neck can be rejuvenated by a redraping solution, such as skin tightening with high frequency ultrasound or radiofrequency ablation.

Sometimes, a clean, tight sweep of jawline can be restored with dermal fillers to the lower face, along with a noninvasive fat reduction approach, said Dr. Keaney.

Knowing men’s unique anatomy and aging patterns is only half the battle, though. “How you communicate with men and evaluate them has to take into account that you might be seeing a sweaty, nervous, treatment-naive patient,” at the initial consultation, said Dr. Keaney. “Do men care? Yes, but men display a different set of motivations.”

Plan for all of this to take time. “The initial consultation tends to be longer” for male patients, who are “less savvy” about cosmetic procedures than women, he pointed out.

A clear discussion of side effects is critical when discussing treatment options with men. “If they get a side effect, you’ll never see them again – and you won’t ever hear about it,” he added.

Though overall, women have been shown to be more sensitive to pain, in cosmetic procedures, “men are less tolerant of pain.” Plan for this, set reasonable expectations but be proactive about pain control, and still expect a need for some hand-holding, said Dr. Keaney.

“Men do not like surprises,” he added. Clearly define what expected side effects may be, what they’ll look like, and what downtime the patient should expect.

For Dr. Keaney’s part, he’s found that the best way to retain men in his cosmetic practice is to “start with a home run treatment to earn trust.” Men often appreciate a slow and steady approach to addressing concerns. “Make sure to connect the treatment plan to the primary cosmetic concern.”

Dr. Keaney reported that he has relationships with multiple pharmaceutical and cosmetic companies.

koakes@mdedge.com

ORLANDO – The first time a man walks in for an aesthetic consultation, he probably doesn’t know what to expect, according to Terrence Keaney, MD, a dermatologist in private practice in Arlington, Va. And he may not even be sure what he’s looking for.

However, he probably knows what he doesn’t like about his appearance. When men are questioned, the three areas they are most concerned about is their hairline, their eyes, and their jawline, said Dr. Keaney, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.

It’s important to evaluate men differently, not just for anatomic differences from women, but also for behavioral and psychological factors unique to men as aesthetic patients, he noted.

Anatomic differences are significant and fundamentally shape treatment decisions, Dr. Keaney said. Broadly speaking, “the male face is traditionally more square, with a prominent supraorbital ridge.” Rather than emphasizing breadth across the cheeks, as in rejuvenation for women, a strong, youthful male face will have a square jaw, appropriate width across the cheeks, and a strong brow line with an arch that is flatter than what women seek.

Male cosmetic goals can be complicated by the fact that men “age poorly” and tend to look older than their stated age, he continued, referring to a study that found that men appear about one-third year older than their age, and women about a half year younger. A higher rate of smoking and excess ultraviolet light exposure among men may contribute to this discrepancy, he said.

Overall, men see steady atrophy of facial soft tissue throughout adulthood, in contrast to women who see a more rapid decline that starts at menopause. This makes sense in the context of the slow drop in circulating testosterone that men see beginning at about age 30, at which time men can expect a decrease of about 1% per year, he noted.

A common opener from men, said Dr. Keaney, is “’I look tired.’ When I hear that, I’m thinking about the eyes.” Men are more likely to develop tear troughs and a sunken appearance because of their larger orbital cavities and smaller orbital fat pads, so periocular fillers are often a treatment tool to consider.

Around mens’ eyes, “it’s not just the presence, but the pattern of wrinkles that guides treatment,” he noted. At the lateral canthi, both at rest and with maximum smile, the predominant wrinkle pattern in crows’ feet is the lower fan. The cheek elevator musculature, including the zygomaticus major, are more involved in animation around the eyes with smiling, which is important because reaching for botulinum toxin alone is probably not going to give the patient his desired effect, he added.

Other differences in the male wrinkle pattern can be found on the brow. The “U” contraction pattern between the brows is more common in men than women, at least partly because men have greater involvement of the procerus muscle, Dr. Keaney said.

Taking all of this into account, caution is the watchword when using botulinum toxin for the glabellar and brow region. “Beware of eyebrow ptosis: avoid the frontalis in patients with eyebrow ptosis,” he said. Treating the corrugators can also be an unwise move, since toxin can diffuse to the inferior fibers of the frontalis muscle, he added.

For men with jawline concerns, consider a combination approach, Dr. Keaney said. The lower face and neck can be rejuvenated by a redraping solution, such as skin tightening with high frequency ultrasound or radiofrequency ablation.

Sometimes, a clean, tight sweep of jawline can be restored with dermal fillers to the lower face, along with a noninvasive fat reduction approach, said Dr. Keaney.

Knowing men’s unique anatomy and aging patterns is only half the battle, though. “How you communicate with men and evaluate them has to take into account that you might be seeing a sweaty, nervous, treatment-naive patient,” at the initial consultation, said Dr. Keaney. “Do men care? Yes, but men display a different set of motivations.”

Plan for all of this to take time. “The initial consultation tends to be longer” for male patients, who are “less savvy” about cosmetic procedures than women, he pointed out.

A clear discussion of side effects is critical when discussing treatment options with men. “If they get a side effect, you’ll never see them again – and you won’t ever hear about it,” he added.

Though overall, women have been shown to be more sensitive to pain, in cosmetic procedures, “men are less tolerant of pain.” Plan for this, set reasonable expectations but be proactive about pain control, and still expect a need for some hand-holding, said Dr. Keaney.

“Men do not like surprises,” he added. Clearly define what expected side effects may be, what they’ll look like, and what downtime the patient should expect.

For Dr. Keaney’s part, he’s found that the best way to retain men in his cosmetic practice is to “start with a home run treatment to earn trust.” Men often appreciate a slow and steady approach to addressing concerns. “Make sure to connect the treatment plan to the primary cosmetic concern.”

Dr. Keaney reported that he has relationships with multiple pharmaceutical and cosmetic companies.

koakes@mdedge.com

BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.

Mitchel L. Zoler/MDedge News

The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.

The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.

When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.

The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.

The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.

Mitchel L. Zoler/MDedge News

But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.

“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.

The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.

Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.

The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.

Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.

CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.

mzoler@mdedge.com

BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.

Mitchel L. Zoler/MDedge News

The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.

The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.

When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.

The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.

The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.

Mitchel L. Zoler/MDedge News

But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.

“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.

The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.

Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.

The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.

Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.

CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.

mzoler@mdedge.com

BOSTON – Ablation of atrial fibrillation led to significantly better quality of life improvements, compared with antiarrhythmic drug therapy, in a prespecified, secondary analysis of data from the CABANA multicenter, randomized trial with 2,204 patients.

Mitchel L. Zoler/MDedge News

The improvements in quality of life measures in atrial fibrillation (AF) patients following ablation were “clinically meaningful” relative to drug therapy and were sustained for 5 years of follow-up, said Douglas L. Packer, MD, at the annual International AF Symposium.

The apparent incremental benefit in quality of life after ablation, compared with patients treated with drug therapy, added to the benefits previously reported from CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial) using ablation that included a highly significant reduction in recurrent AF and a significant reduction in the combined endpoint of mortality or cardiovascular hospitalization. However, the trial’s results were neutral for the study’s prespecified primary endpoint, a combination of the rate of total mortality, disabling stroke, serious bleeding, or cardiac arrest in an intention-to-treat analysis, a result first reported by Dr. Packer at the annual scientific sessions of the Heart Rhythm Society in May 2018.

When Dr. Packer spoke at the AF Symposium in late January 2019, the CABANA results had still not been published. He said that he expected an article with the main findings to appear online sometime in February 2019.

The quality of life analysis, focused on two measures, the Mayo AF-Specific Symptoms Inventory (MAFSI) (Circulation. 2008 Oct 28;118[suppl 18]:S589) and the Atrial Fibrillation Affect on Quality of Life (AFEQT) (Circ Arrhythm Electrophysiol. 2011 Feb;4[1]:15-25). The patients enrolled in the two treatment arms of CABANA had essentially identical baseline MAFSI frequency scores, but starting 3 months after entry patients randomized to the ablation arm had an average, statistically significant 1.6-point improvement in their adjusted MAFSI frequency score, compared with patients in the drug-therapy arm; this reduction persisted at about the same statistically significant level through 5 years, said Dr. Packer, an electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn., and lead investigator of CABANA. Patients who remained in follow-up throughout the study’s entire 60 months underwent a total of seven MAFSI assessments after their initial treatment; the average, adjusted difference in MAFSI frequency scores throughout CABANA was a statistically significant 1.4 points lower among ablated patients, compared with those randomized to drug therapy, said Dr. Packer, who presented data first reported by the CABANA researchers in 2018.

The pattern of change in the AFEQT scores was very similar. The average, adjusted AFEQT summary scores were virtually identical at baseline for the two treatment arms, but at 3 months after the study began patients in the ablation arm had an average, adjusted, statistically significant 3-point improvement in their AFEQT summary scores, compared with drug-treated patients; this incremental increase in AFEQT scores remained consistent and statistically significant through 5 years of follow-up. Throughout the study, the average, adjusted, incremental improvement in AFEQT after ablation was a statistically significant 3.4 points, said Dr. Packer.

Mitchel L. Zoler/MDedge News

But these quality of life measures in patients who received unblinded assignment to an ablation procedure or drug treatment in CABANA are likely unreliable, commented Peter R. Kowey, MD, an electrophysiologist at the Lankenau Heart Institute in Wynnewood, Penn., and professor of medicine at Jefferson Medical College, Philadelphia.

“Assessing quality of life in an unblinded trial seems to me to be pretty shallow,” said Dr. Kowey, a member of the CABANA steering committee and a participant in a panel at the Symposium that discussed the results. Patients who have just gone through a 6-hour procedure will often say they now feel a whole lot better, he suggested. “They’re concerned what will get done to them if they don’t say they feel better.” The same confounding also applies to other “soft” secondary endpoints used in CABANA, such as hospitalization rates.

The reliability of these more subjective outcome measures is reduced in an unblinded trial, Dr. Kowey maintained. The CABANA results “don’t change the fundamental principal of using hard endpoints,” such as those that made up the primary endpoint of the study, he said in an interview. “We put secondary endpoints into the study because they are legitimate things to look at, but they have questionable reliability,” as measures of ablation’s efficacy.

Dr. Kowey also cautioned against focusing on the per-protocol and treatment-received analyses of the CABANA results, prespecified analyses that Dr. Packer highlighted because of the high number of crossovers in the trial: 9% of patients assigned to ablation never received it and 28% of patients assigned to drug therapy actually received ablation.

The CABANA steering committee anticipated a high crossover rate, but still set the intention-to-treat analysis as primary because “per protocol introduces many biases and can’t be relied on for a study of this magnitude,” Dr. Kowey said. He also cited the statistical pitfalls of looking at multiple secondary endpoints in the CABANA results and the danger of reading too much into subgroup analyses, all from a trial with a neutral primary endpoint.

Another concern he raised centered on the generalizability of CABANA’s safety findings, which showed roughly similar adverse event rates between the two treatment arms – about 9% with ablation, 4% with drugs – although the distribution of complications types differed between the two arms. The “ ‘remarkably safe’ performance of ablation in CABANA can be attributed to ‘cherry-picked’ investigators” who performed the ablation procedures at high-volume centers, said Dr. Kowey. “The safety of ablation was predictable” in CABANA because of the selection of participating centers. “Seventy percent of U.S. ablations are being done at centers that do fewer than 25 ablations annually,” Dr. Kowey said. “We don’t know what goes on” at lower-volume centers; “ablation can’t be considered as safe as we presume” when done at centers outside the 118 sites that participated in CABANA, he maintained.

CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to these four companies as well as to CyberHeart, nContact, Sanofi-Aventis, and Toray. He has received research funding from AG, Biosense Webster, Boston Scientific, CryoCath, EP Limited, and Medtronic, and has a financial interest in AF mapping technology. Dr. Kowey has been a consultant to several companies that market antiarrhythmic drugs or market arrhythmia devices and has an equity interest in BioTelemetry.

mzoler@mdedge.com

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

dbrunk@mdedge.com

SOURCE: Chung D et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

dbrunk@mdedge.com

SOURCE: Chung D et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Raw data from the Fitbit and sleep applications for smartphones should not be recommended as screening tools for obstructive sleep apnea, results from a single-center study suggest.

Doug Brunk/MDedge News

“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”

According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.

“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”

In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.

Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.

“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.

He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”

Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
 

dbrunk@mdedge.com

SOURCE: Chung D et al. Triological CSM, Abstracts.

Clinical question: What are the causes and risks of mortality in the first year after nonfatal opioid overdose?

Background: The current opioid epidemic has led to increasing hospitalizations and ED presentations for nonfatal opioid overdose. Despite this, little is known about the subsequent causes of mortality in these patients. Additional information could suggest potential interventions to decrease subsequent risk of death.

Study design: Retrospective cohort study.

Setting: U.S. national cohort of Medicaid beneficiaries, aged 18-64 years, during 2001-2007.

Dr. Breviu is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Clinical question: What are the causes and risks of mortality in the first year after nonfatal opioid overdose?

Background: The current opioid epidemic has led to increasing hospitalizations and ED presentations for nonfatal opioid overdose. Despite this, little is known about the subsequent causes of mortality in these patients. Additional information could suggest potential interventions to decrease subsequent risk of death.

Study design: Retrospective cohort study.

Setting: U.S. national cohort of Medicaid beneficiaries, aged 18-64 years, during 2001-2007.

Dr. Breviu is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Clinical question: What are the causes and risks of mortality in the first year after nonfatal opioid overdose?

Background: The current opioid epidemic has led to increasing hospitalizations and ED presentations for nonfatal opioid overdose. Despite this, little is known about the subsequent causes of mortality in these patients. Additional information could suggest potential interventions to decrease subsequent risk of death.

Study design: Retrospective cohort study.

Setting: U.S. national cohort of Medicaid beneficiaries, aged 18-64 years, during 2001-2007.

Dr. Breviu is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs form the basis for the development of drugs used in everyday clinical practice, such as commonly used insulin products. PK measures the concentration of a drug in the body, and reflects the rates and amounts absorbed and processed. PD is the biologic effect of a drug in the body, including the time-course of when the biologic effect starts, peaks, and ends. While the determination of PK/PD parameters is important and foundational for the development of different insulin products, studies are often complex and can be difficult to translate into real-world clinical practice. In this roundtable, the speakers discuss PK/PD concepts, focusing on the differentiation of basal insulin analogs and their use in individualized diabetes therapy.

First, the speakers discuss the euglycemic glucose clamp methodology—the standard technique for evaluating PK/PD of insulin—including how it is performed, what parameters it measures (and how they can be interpreted), and its limitations.

Next, the speakers discuss how PK/PD impacts drug development, with particular focus on PK/PD studies used in the development of the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) and insulin degludec.

Finally, the speakers discuss how PK/PD data translate into clinical practice, including the relationship between PK/PD and drug efficacy and safety, and how it influences dosing strategies, hypoglycemia risk, and patient education. Further, the speakers discuss how the PK/PD profile of basal insulins can inform primary care providers when selecting appropriate individualized therapy for patients.

Financial support provided by Sanofi US, Inc.

Click here to watch the videos

Pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs form the basis for the development of drugs used in everyday clinical practice, such as commonly used insulin products. PK measures the concentration of a drug in the body, and reflects the rates and amounts absorbed and processed. PD is the biologic effect of a drug in the body, including the time-course of when the biologic effect starts, peaks, and ends. While the determination of PK/PD parameters is important and foundational for the development of different insulin products, studies are often complex and can be difficult to translate into real-world clinical practice. In this roundtable, the speakers discuss PK/PD concepts, focusing on the differentiation of basal insulin analogs and their use in individualized diabetes therapy.

First, the speakers discuss the euglycemic glucose clamp methodology—the standard technique for evaluating PK/PD of insulin—including how it is performed, what parameters it measures (and how they can be interpreted), and its limitations.

Next, the speakers discuss how PK/PD impacts drug development, with particular focus on PK/PD studies used in the development of the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) and insulin degludec.

Finally, the speakers discuss how PK/PD data translate into clinical practice, including the relationship between PK/PD and drug efficacy and safety, and how it influences dosing strategies, hypoglycemia risk, and patient education. Further, the speakers discuss how the PK/PD profile of basal insulins can inform primary care providers when selecting appropriate individualized therapy for patients.

Financial support provided by Sanofi US, Inc.

Click here to watch the videos

Pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs form the basis for the development of drugs used in everyday clinical practice, such as commonly used insulin products. PK measures the concentration of a drug in the body, and reflects the rates and amounts absorbed and processed. PD is the biologic effect of a drug in the body, including the time-course of when the biologic effect starts, peaks, and ends. While the determination of PK/PD parameters is important and foundational for the development of different insulin products, studies are often complex and can be difficult to translate into real-world clinical practice. In this roundtable, the speakers discuss PK/PD concepts, focusing on the differentiation of basal insulin analogs and their use in individualized diabetes therapy.

First, the speakers discuss the euglycemic glucose clamp methodology—the standard technique for evaluating PK/PD of insulin—including how it is performed, what parameters it measures (and how they can be interpreted), and its limitations.

Next, the speakers discuss how PK/PD impacts drug development, with particular focus on PK/PD studies used in the development of the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) and insulin degludec.

Finally, the speakers discuss how PK/PD data translate into clinical practice, including the relationship between PK/PD and drug efficacy and safety, and how it influences dosing strategies, hypoglycemia risk, and patient education. Further, the speakers discuss how the PK/PD profile of basal insulins can inform primary care providers when selecting appropriate individualized therapy for patients.

Financial support provided by Sanofi US, Inc.

Click here to watch the videos

The Food and Drug Administration (FDA) has granted breakthrough therapy designation to umbralisib for the treatment of adults with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 regimen.

Umbralisib (formerly TGR-1202) is a PI3K-delta inhibitor being developed by TG Therapeutics.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance and other actions that may expedite FDA review. For a treatment to earn breakthrough designation, early clinical results must show that it provides improvement over available therapies or fulfills an unmet need.

The breakthrough designation for umbralisib was based on interim data from the MZL cohort in the ongoing, phase 2b UNITY-NHL trial (NCT02793583).

In this trial, researchers are testing umbralisib alone or in combination with ublituximab, with or without bendamustine, in patients with previously treated non-Hodgkin lymphoma.

“The MZL single-agent umbralisib cohort of the UNITY-NHL study is fully enrolled, and we look forward to reporting topline results from this cohort by mid-year and presenting the data at a major medical meeting in 2019,” Michael S. Weiss, chief executive officer of TG Therapeutics, said in a statement.

Umbralisib monotherapy was previously evaluated in a phase 1 trial (NCT01767766) of patients with relapsed or refractory B-cell malignancies (Lancet Oncol. 2018 Apr;19[4]:486-96).

The trial enrolled 90 patients, and five of them had MZL. A total of 33 patients achieved a response to umbralisib. This includes one MZL patient who achieved a partial response.

The most common treatment-emergent adverse events (AEs) in this trial were diarrhea, nausea, and fatigue. The most common grade 3/4 AEs were neutropenia, anemia, and thrombocytopenia.

Serious AEs considered at least possibly related to umbralisib were pneumonia, lung infection, febrile neutropenia, and colitis. There were no treatment-related deaths.

jensmith@mdedge.com

The Food and Drug Administration (FDA) has granted breakthrough therapy designation to umbralisib for the treatment of adults with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 regimen.

Umbralisib (formerly TGR-1202) is a PI3K-delta inhibitor being developed by TG Therapeutics.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance and other actions that may expedite FDA review. For a treatment to earn breakthrough designation, early clinical results must show that it provides improvement over available therapies or fulfills an unmet need.

The breakthrough designation for umbralisib was based on interim data from the MZL cohort in the ongoing, phase 2b UNITY-NHL trial (NCT02793583).

In this trial, researchers are testing umbralisib alone or in combination with ublituximab, with or without bendamustine, in patients with previously treated non-Hodgkin lymphoma.

“The MZL single-agent umbralisib cohort of the UNITY-NHL study is fully enrolled, and we look forward to reporting topline results from this cohort by mid-year and presenting the data at a major medical meeting in 2019,” Michael S. Weiss, chief executive officer of TG Therapeutics, said in a statement.

Umbralisib monotherapy was previously evaluated in a phase 1 trial (NCT01767766) of patients with relapsed or refractory B-cell malignancies (Lancet Oncol. 2018 Apr;19[4]:486-96).

The trial enrolled 90 patients, and five of them had MZL. A total of 33 patients achieved a response to umbralisib. This includes one MZL patient who achieved a partial response.

The most common treatment-emergent adverse events (AEs) in this trial were diarrhea, nausea, and fatigue. The most common grade 3/4 AEs were neutropenia, anemia, and thrombocytopenia.

Serious AEs considered at least possibly related to umbralisib were pneumonia, lung infection, febrile neutropenia, and colitis. There were no treatment-related deaths.

jensmith@mdedge.com

The Food and Drug Administration (FDA) has granted breakthrough therapy designation to umbralisib for the treatment of adults with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 regimen.

Umbralisib (formerly TGR-1202) is a PI3K-delta inhibitor being developed by TG Therapeutics.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance and other actions that may expedite FDA review. For a treatment to earn breakthrough designation, early clinical results must show that it provides improvement over available therapies or fulfills an unmet need.

The breakthrough designation for umbralisib was based on interim data from the MZL cohort in the ongoing, phase 2b UNITY-NHL trial (NCT02793583).

In this trial, researchers are testing umbralisib alone or in combination with ublituximab, with or without bendamustine, in patients with previously treated non-Hodgkin lymphoma.

“The MZL single-agent umbralisib cohort of the UNITY-NHL study is fully enrolled, and we look forward to reporting topline results from this cohort by mid-year and presenting the data at a major medical meeting in 2019,” Michael S. Weiss, chief executive officer of TG Therapeutics, said in a statement.

Umbralisib monotherapy was previously evaluated in a phase 1 trial (NCT01767766) of patients with relapsed or refractory B-cell malignancies (Lancet Oncol. 2018 Apr;19[4]:486-96).

The trial enrolled 90 patients, and five of them had MZL. A total of 33 patients achieved a response to umbralisib. This includes one MZL patient who achieved a partial response.

The most common treatment-emergent adverse events (AEs) in this trial were diarrhea, nausea, and fatigue. The most common grade 3/4 AEs were neutropenia, anemia, and thrombocytopenia.

Serious AEs considered at least possibly related to umbralisib were pneumonia, lung infection, febrile neutropenia, and colitis. There were no treatment-related deaths.

jensmith@mdedge.com

Positive well-being might function as a “resilient factor against depression” in autism spectrum disorder, results of a 12-month study of newly employed adults with ASD suggest.

“The potential for positive well-being to functioning as a buffer against depression in this study, as well as the broader benefits of positive well-being in the general population, suggests that positive well-being should be cultivated within the employment context,” wrote Darren Hedley, PhD, of La Trobe University, Melbourne, and his associates (Autism Res. 2019 Jan 24. doi: 10.1002/aur/2064).

To conduct the study, Dr. Hedley and his associates tested 36 (32 male) adults aged 18-57 with ASD who worked in an employment program supported by the Australian government. Among the measures used to assess mental health, social support, and job satisfaction were the Patient Health Questionnaire-9, the DSM-5 Dimensional Anxiety Scale, the Warwick-Edinburgh Mental Wellbeing Scale, the Interpersonal Support Evaluation List-12, and the Minnesota Satisfaction Questionnaire-Short Form.

Over the course of 12 months, Dr. Hedley and his associates found that the participants experienced a small increase in their daily living skills and a small drop in job satisfaction, but all other measures – except for depression – remained stable. In the case of depressive symptoms, a negative correlation was found between baseline positive well-being and depression at follow-up. “These results are consistent with research in the general population that shows well-being functions as a buffer or protective factor against depression,” they wrote.

Dr. Hedley and his associates cited several limitations, including the small sample size and the absence of a comparative sample of adults with ASD engaged in open employment.

The full study can be found at Autism Research.

cpalmer@mdedge.com

Positive well-being might function as a “resilient factor against depression” in autism spectrum disorder, results of a 12-month study of newly employed adults with ASD suggest.

“The potential for positive well-being to functioning as a buffer against depression in this study, as well as the broader benefits of positive well-being in the general population, suggests that positive well-being should be cultivated within the employment context,” wrote Darren Hedley, PhD, of La Trobe University, Melbourne, and his associates (Autism Res. 2019 Jan 24. doi: 10.1002/aur/2064).

To conduct the study, Dr. Hedley and his associates tested 36 (32 male) adults aged 18-57 with ASD who worked in an employment program supported by the Australian government. Among the measures used to assess mental health, social support, and job satisfaction were the Patient Health Questionnaire-9, the DSM-5 Dimensional Anxiety Scale, the Warwick-Edinburgh Mental Wellbeing Scale, the Interpersonal Support Evaluation List-12, and the Minnesota Satisfaction Questionnaire-Short Form.

Over the course of 12 months, Dr. Hedley and his associates found that the participants experienced a small increase in their daily living skills and a small drop in job satisfaction, but all other measures – except for depression – remained stable. In the case of depressive symptoms, a negative correlation was found between baseline positive well-being and depression at follow-up. “These results are consistent with research in the general population that shows well-being functions as a buffer or protective factor against depression,” they wrote.

Dr. Hedley and his associates cited several limitations, including the small sample size and the absence of a comparative sample of adults with ASD engaged in open employment.

The full study can be found at Autism Research.

cpalmer@mdedge.com

Positive well-being might function as a “resilient factor against depression” in autism spectrum disorder, results of a 12-month study of newly employed adults with ASD suggest.

“The potential for positive well-being to functioning as a buffer against depression in this study, as well as the broader benefits of positive well-being in the general population, suggests that positive well-being should be cultivated within the employment context,” wrote Darren Hedley, PhD, of La Trobe University, Melbourne, and his associates (Autism Res. 2019 Jan 24. doi: 10.1002/aur/2064).

To conduct the study, Dr. Hedley and his associates tested 36 (32 male) adults aged 18-57 with ASD who worked in an employment program supported by the Australian government. Among the measures used to assess mental health, social support, and job satisfaction were the Patient Health Questionnaire-9, the DSM-5 Dimensional Anxiety Scale, the Warwick-Edinburgh Mental Wellbeing Scale, the Interpersonal Support Evaluation List-12, and the Minnesota Satisfaction Questionnaire-Short Form.

Over the course of 12 months, Dr. Hedley and his associates found that the participants experienced a small increase in their daily living skills and a small drop in job satisfaction, but all other measures – except for depression – remained stable. In the case of depressive symptoms, a negative correlation was found between baseline positive well-being and depression at follow-up. “These results are consistent with research in the general population that shows well-being functions as a buffer or protective factor against depression,” they wrote.

Dr. Hedley and his associates cited several limitations, including the small sample size and the absence of a comparative sample of adults with ASD engaged in open employment.

The full study can be found at Autism Research.

cpalmer@mdedge.com

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

dbrunk@mdedge.com

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The next presidential primary contests are more than a year away. But presumed candidates are already trying to stake a claim to one of health care’s hot-button concerns: surging prescription drug prices.

Kenishirotie/Thinkstock

“This is a 2020 thing,” said Peter B. Bach, MD, who directs the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and tracks drug-pricing policy.

Spurred on by midterm election results that showed health care to be a deciding issue, lawmakers – some of whom have already launched presidential-run exploratory committees – are pushing a bevy of new proposals and approaches.

Few if any of those ideas will likely make it to the president’s desk. Nevertheless, Senate Democrats eyeing higher office and seeking street cred in the debate are devising more innovative and aggressive strategies to take on Big Pharma.

“Democrats feel as if they’re really able to experiment,” said Rachel Sachs, an associate law professor at Washington University, St. Louis, who tracks drug-pricing laws.

Some Republicans are also proposing drug-pricing reform, although experts say their approaches are generally less dramatic.

Here are some of the ideas either introduced in legislation or that senators’ offices confirmed they are considering:

• Make a public option for generic drugs. The government could manufacture generics (directly or through a private contractor) if there is a shortage or aren’t enough competitors to keep prices down. This comes from a bill put forth by Sen. Elizabeth Warren (D-Mass.) and Rep. Jan Schakowsky (D-Ill.).
• Let Medicare negotiate drug prices. This idea has many backers – what differs is the method of enforcement. Sen. Sherrod Brown (D-Ohio) has suggested that if the company and the government can’t reach an agreement, the government could take away the company’s patent rights. A proposal from Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) would address stalled negotiations by letting Medicare pay the lowest amount among: Medicaid’s best price, the highest price a single federal purchaser pays or the median price paid for a specific drug in Canada, France, Germany, Japan, and the United Kingdom.
• Pay what they do abroad. Legislation from Mr. Sanders and Rep. Ro Khanna (D-Calif.) would require companies to price their drugs no higher than the median of what’s charged in Canada, France, Germany, Japan, and the United Kingdom. If manufacturers fail to comply, other companies could get the rights to make those drugs, too.
• Penalize price gouging. This would target manufacturers who raise drug prices more than 30% in 5 years. Punishments could include requiring the company to reimburse those who paid the elevated price, forcing the drug maker to lower its price, or charging a penalty up to three times what a company received from boosting the price. Backers include senators Richard Blumenthal (D-Conn.), Kamala Harris (D-Calif.), Jeff Merkley (D-Ore.), and Amy Klobuchar (D-Minn.).
• Import drugs. A Sanders-Cummings bill would let patients, wholesalers, and pharmacies import drugs from abroad – starting with Canada, and leaving the door open for some other countries. Sen. Chuck Grassley (R-Iowa) and Ms. Klobuchar have a separate bill that is specific to patients getting medicine from Canada alone.
• Abolish “pay for delay.” From Mr. Grassley and Ms. Klobuchar, this legislation would tackle deals in which a branded drugmaker pays off a generic one to keep a competing product from coming to market.

This flurry of proposed lawmaking could add momentum to one of the few policy areas in which conventional Washington wisdom suggests House Democrats, Senate Republicans, and the White House may be able to find common ground.

“Everything is up in the air and anything is possible,” said Walid Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “There are things that can happen that maybe weren’t going to happen before.”

And there’s political pressure. Polls consistently suggest voters have a strong appetite for action. As a candidate, President Trump vowed to make drug prices a top priority. In recent months, the administration has taken steps in this direction, like testing changes to Medicare that might reduce out-of-pocket drug costs. But Congress has been relatively quiet, especially when it comes to challenging the pharmaceutical industry, which remains one of Capitol Hill’s most potent lobbying forces.

One aspect of prescription drug pricing that could see bipartisan action is insulin prices, which have skyrocketed, stoking widespread outcry, and could be a target for bipartisan work. Ms. Warren’s legislation singles out the drug as one the government could produce, and Mr. Cummings has already called in major insulin manufacturers for a drug-pricing hearing later this month. In addition, Rep. Diana DeGette (D-Colo.), the new chair of the House Energy and Commerce Oversight and Investigations Subcommittee, has listed prescription drug pricing as a high priority for her panel. As cochair of the Congressional Diabetes Caucus, Ms. DeGette worked with Rep. Tom Reed (R-N.Y.) to produce a report on the high cost of insulin.

To be sure, some of the concepts, such as drug importation and bolstering development of generic drugs, have been around a long time. But some of the legislation at hand suggests a new kind of thinking.

House Speaker Nancy Pelosi (D-Calif.) has labeled drug pricing a top priority, and the pharmaceutical industry has been bracing for a fight with the new Democratic majority.

Meanwhile, in the GOP-controlled Senate, two powerful lawmakers – Sen. Lamar Alexander (R-Tenn.) and Mr. Grassley – have indicated they want to use their influence to tackle the issue. Mr. Alexander, who chairs the Health, Education, Labor and Pensions Committee, has said cutting health care costs, including drug prices, will be high on his panel’s to-do list this Congress. Mr. Grassley runs the Finance Committee, which oversees pricing issues for Medicare and Medicaid.

“The solution to high drug prices is not just having the government spending more money. ... You need to look at prices,” Dr. Gellad said. “These proposals deal with price. They all directly affect price.”

Given the drug industry’s full-throated opposition to virtually any pricing legislation, Ms. Sachs said, “it is not at all surprising to me to see the Democrats start exploring some of these more radical proposals.”

Still, though, Senate staffers almost uniformly argued that the drug-pricing issue requires more than one single piece of legislation.

For instance, the price-gouging penalty spearheaded by Mr. Blumenthal doesn’t stop drugs from having high initial list prices. Letting Medicare negotiate doesn’t mean people covered by other plans will necessarily see the same savings. Empowering the government to produce competing drugs doesn’t promise to keep prices down long term and doesn’t guarantee that patients will see those savings.

“We need to use every tool available to bring down drug prices and improve competition,” said an aide in Ms. Warren’s office.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com

LAS VEGAS – Deep brain stimulation (DBS) provides motor and nonmotor benefits at 6 months, 1 year, and 2 years after implantation in patients with Parkinson’s disease, according to a large-scale collection of outcome data. The treatment improves motor function and quality of life and has an acceptable safety profile. The analysis was presented at the annual meeting of the North American Neuromodulation Society.

Research by Okun et al. in 2012 and Schuepbach et al. in 2013 demonstrated that DBS effectively reduces the motor complications of Parkinson’s disease. To monitor the treatment’s efficacy and safety on a large scale, investigators established a prospective registry of patients with levodopa-responsive Parkinson’s disease who underwent DBS implantation. An aim of the registry is to improve understanding of the clinical use and outcomes of DBS in this population. As many as 1,000 patients have been implanted with Vercise DBS systems at 70 international sites. These systems enable multiple independent current source control.

Participants presented for clinical visits at 3 months, 6 months, 1 year, 2 years, and 3 years after surgery. Jan Vesper, MD, PhD, professor of neurosurgery at Heinrich Heine University in Düsseldorf, Germany, and his colleagues analyzed patient outcomes, including the Parkinson’s Disease Questionnaire (PDQ-39), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Clinical Global Impression of Change (as assessed by the patient, caregiver, and clinician), and the Schwab and England (SE) scale. The researchers also reported adverse events.

As of November 2018, 403 participants had been enrolled in the registry, and 359 had undergone DBS implantation. At baseline, mean age was 59.6 years, and approximately 70% of participants were male. Mean disease duration was 10.4 years. Without medication, mean MDS-UPDRS III score was 44.8, and mean PDQ-39 Summary Index score was 28.8.

At 1 year, participants’ mean off-medication MDS-UPDRS III score was 29.7. This result represented a significant 34% improvement in motor performance.

PDQ-39 Summary Index score was improved by 6.7 points at 6 months, 4.7 points at 1 year, and 3.0 points at 2 years, which represented a sustained benefit for participants’ quality of life. Improvements in activities of daily living were sustained throughout the 2-year period. Cognition was improved at 6 months, but not at subsequent visits. Mobility, stigma, and bodily discomfort were improved at 6 months and 1 year, but not at 2 years. Furthermore, more than 80% of patients, caregivers, and clinicians observed improvements in Parkinson’s disease symptoms at all time points.

The investigators did not find any unanticipated adverse events. In all, 217 serious adverse events occurred in 121 participants. Of these events, 60 were related to stimulation. No lead fractures or breakages occurred.

“This registry represents the first large-scale collection of outcomes using a DBS system capable of multiple independent current source control,” said Dr. Vesper and colleagues.

The investigators did not report any conflicts of interest.
 

egreb@mdedge.com