Bruce Jancin

CHICAGO – A novel genomic analysis technique known as exome analysis has pinpointed two previously unsuspected genes strongly related to platelet reactivity in patients on clopidogrel.

A hoped-for practical outcome from this finding is development of a rapid test for clopidogrel responsiveness. Before undergoing percutaneous coronary intervention, a swab could be run through a patient’s mouth and a quick analysis of the genetic sample would indicate whether clopidogrel would be an effective antiplatelet agent in that individual. Current assays require patients to already be on clopidogrel, which may or may not be providing them protection.

P hoto: Bruce Jancin/IMNG Medical Media

Dr. Matthew J. Price, director of the cardiac catheterization laboratory at the Scripps Clinic, La Jolla, Calif. presented the findings of the Genotype Information and Functional Testing Exome (GIFT EXOME) study, in which he and his coworkers performed whole exome analysis on genetic material obtained from 192 self-identified white participants in the earlier GRAVITAS (Gauging Responsiveness with A VerifyNow P2Y12 assay – Impact on Thrombosis And Safety) trial. That study, for which Dr. Price served as principal investigator, showed no benefit for double-dose clopidogrel in patients with high on-treatment platelet reactivity after percutaneous coronary intervention (JAMA 2011;305:1097-105).

In GIFT EXOME, three distinct genes were found to be associated with on-treatment platelet reactivity 12-24 hours post-PCI in patients taking clopidogrel. One of them, CYP2C18/9, was already known to be associated with platelet resistance to clopidogrel, although variants in this gene explain only a small portion of the overall variability in clopidogrel response. The finding of the other two genes, ATP2B2 and TIAM2, came as a surprise.

The ATP2B2 gene codes for a plasma membrane calcium transporting ATPase. It exports calcium ions out of the cell, so it plays a critical role in maintaining intracellular calcium homeostasis, thereby influencing platelet activation and aggregation, the cardiologist explained at the annual meeting of the American College of Cardiology.

TIAM2 (T-cell lymphoma invasion and metastasis 2) is the primary mediator of activation of a protein called Rac1, which is involved in platelet aggregation.

"These findings are preliminary, but identification of two genes critical to platelet function among the 21,000 genes we sequenced lends credibility to the validity of the result," Dr. Price observed.

The overall frequency of the ATP2B2 variant linked to platelet activity in the presence of clopidogrel is 27% in the white population, while for the key TIAM2 variant it’s about 13%, he said.

The next step in the GIFT EXOME project is to validate the results in more than 1,000 patients, an effort already underway.

As an aside, eight subjects in GIFT EXOME turned out to have genomes inconsistent with white race and were excluded from the study.

Whole exome analysis entails sequencing the entire protein-coding regions of the human genome. This high-powered technique identifies both single nucleotide polymorphisms and insertion/deletions. Exome analysis is far more likely to identify specific gene mutations that are causative of disease than is the older, widely utilized method of genome-wide association studies, which basically points investigators toward what Dr. Price calls "zip codes" of interest along the genome without zeroing in on specific culprit genes.

He said that the major challenge posed by whole exome analysis is the enormous computational muscle required. More than 400 days of serial supercomputer time went into analyzing the samples from 192 GIFT EXOME participants. In excess of 6.1 million single nucleotide polymorphisms and more than 500,000 insertion/deletions were detected. Computers are getting ever faster, though, and the reagents required for exome sequencing are getting more affordable, he noted.

The GIFT EXOME study was supported by Bristol-Myers Squibb/Sanofi. Dr. Price reported serving as a consultant to those companies and more than half a dozen others. He also holds an equity interest in Iverson Genetics.

CHICAGO – A novel genomic analysis technique known as exome analysis has pinpointed two previously unsuspected genes strongly related to platelet reactivity in patients on clopidogrel.

A hoped-for practical outcome from this finding is development of a rapid test for clopidogrel responsiveness. Before undergoing percutaneous coronary intervention, a swab could be run through a patient’s mouth and a quick analysis of the genetic sample would indicate whether clopidogrel would be an effective antiplatelet agent in that individual. Current assays require patients to already be on clopidogrel, which may or may not be providing them protection.

P hoto: Bruce Jancin/IMNG Medical Media

Dr. Matthew J. Price, director of the cardiac catheterization laboratory at the Scripps Clinic, La Jolla, Calif. presented the findings of the Genotype Information and Functional Testing Exome (GIFT EXOME) study, in which he and his coworkers performed whole exome analysis on genetic material obtained from 192 self-identified white participants in the earlier GRAVITAS (Gauging Responsiveness with A VerifyNow P2Y12 assay – Impact on Thrombosis And Safety) trial. That study, for which Dr. Price served as principal investigator, showed no benefit for double-dose clopidogrel in patients with high on-treatment platelet reactivity after percutaneous coronary intervention (JAMA 2011;305:1097-105).

In GIFT EXOME, three distinct genes were found to be associated with on-treatment platelet reactivity 12-24 hours post-PCI in patients taking clopidogrel. One of them, CYP2C18/9, was already known to be associated with platelet resistance to clopidogrel, although variants in this gene explain only a small portion of the overall variability in clopidogrel response. The finding of the other two genes, ATP2B2 and TIAM2, came as a surprise.

The ATP2B2 gene codes for a plasma membrane calcium transporting ATPase. It exports calcium ions out of the cell, so it plays a critical role in maintaining intracellular calcium homeostasis, thereby influencing platelet activation and aggregation, the cardiologist explained at the annual meeting of the American College of Cardiology.

TIAM2 (T-cell lymphoma invasion and metastasis 2) is the primary mediator of activation of a protein called Rac1, which is involved in platelet aggregation.

"These findings are preliminary, but identification of two genes critical to platelet function among the 21,000 genes we sequenced lends credibility to the validity of the result," Dr. Price observed.

The overall frequency of the ATP2B2 variant linked to platelet activity in the presence of clopidogrel is 27% in the white population, while for the key TIAM2 variant it’s about 13%, he said.

The next step in the GIFT EXOME project is to validate the results in more than 1,000 patients, an effort already underway.

As an aside, eight subjects in GIFT EXOME turned out to have genomes inconsistent with white race and were excluded from the study.

Whole exome analysis entails sequencing the entire protein-coding regions of the human genome. This high-powered technique identifies both single nucleotide polymorphisms and insertion/deletions. Exome analysis is far more likely to identify specific gene mutations that are causative of disease than is the older, widely utilized method of genome-wide association studies, which basically points investigators toward what Dr. Price calls "zip codes" of interest along the genome without zeroing in on specific culprit genes.

He said that the major challenge posed by whole exome analysis is the enormous computational muscle required. More than 400 days of serial supercomputer time went into analyzing the samples from 192 GIFT EXOME participants. In excess of 6.1 million single nucleotide polymorphisms and more than 500,000 insertion/deletions were detected. Computers are getting ever faster, though, and the reagents required for exome sequencing are getting more affordable, he noted.

The GIFT EXOME study was supported by Bristol-Myers Squibb/Sanofi. Dr. Price reported serving as a consultant to those companies and more than half a dozen others. He also holds an equity interest in Iverson Genetics.

CHICAGO – A novel genomic analysis technique known as exome analysis has pinpointed two previously unsuspected genes strongly related to platelet reactivity in patients on clopidogrel.

A hoped-for practical outcome from this finding is development of a rapid test for clopidogrel responsiveness. Before undergoing percutaneous coronary intervention, a swab could be run through a patient’s mouth and a quick analysis of the genetic sample would indicate whether clopidogrel would be an effective antiplatelet agent in that individual. Current assays require patients to already be on clopidogrel, which may or may not be providing them protection.

P hoto: Bruce Jancin/IMNG Medical Media

Dr. Matthew J. Price, director of the cardiac catheterization laboratory at the Scripps Clinic, La Jolla, Calif. presented the findings of the Genotype Information and Functional Testing Exome (GIFT EXOME) study, in which he and his coworkers performed whole exome analysis on genetic material obtained from 192 self-identified white participants in the earlier GRAVITAS (Gauging Responsiveness with A VerifyNow P2Y12 assay – Impact on Thrombosis And Safety) trial. That study, for which Dr. Price served as principal investigator, showed no benefit for double-dose clopidogrel in patients with high on-treatment platelet reactivity after percutaneous coronary intervention (JAMA 2011;305:1097-105).

In GIFT EXOME, three distinct genes were found to be associated with on-treatment platelet reactivity 12-24 hours post-PCI in patients taking clopidogrel. One of them, CYP2C18/9, was already known to be associated with platelet resistance to clopidogrel, although variants in this gene explain only a small portion of the overall variability in clopidogrel response. The finding of the other two genes, ATP2B2 and TIAM2, came as a surprise.

The ATP2B2 gene codes for a plasma membrane calcium transporting ATPase. It exports calcium ions out of the cell, so it plays a critical role in maintaining intracellular calcium homeostasis, thereby influencing platelet activation and aggregation, the cardiologist explained at the annual meeting of the American College of Cardiology.

TIAM2 (T-cell lymphoma invasion and metastasis 2) is the primary mediator of activation of a protein called Rac1, which is involved in platelet aggregation.

"These findings are preliminary, but identification of two genes critical to platelet function among the 21,000 genes we sequenced lends credibility to the validity of the result," Dr. Price observed.

The overall frequency of the ATP2B2 variant linked to platelet activity in the presence of clopidogrel is 27% in the white population, while for the key TIAM2 variant it’s about 13%, he said.

The next step in the GIFT EXOME project is to validate the results in more than 1,000 patients, an effort already underway.

As an aside, eight subjects in GIFT EXOME turned out to have genomes inconsistent with white race and were excluded from the study.

Whole exome analysis entails sequencing the entire protein-coding regions of the human genome. This high-powered technique identifies both single nucleotide polymorphisms and insertion/deletions. Exome analysis is far more likely to identify specific gene mutations that are causative of disease than is the older, widely utilized method of genome-wide association studies, which basically points investigators toward what Dr. Price calls "zip codes" of interest along the genome without zeroing in on specific culprit genes.

He said that the major challenge posed by whole exome analysis is the enormous computational muscle required. More than 400 days of serial supercomputer time went into analyzing the samples from 192 GIFT EXOME participants. In excess of 6.1 million single nucleotide polymorphisms and more than 500,000 insertion/deletions were detected. Computers are getting ever faster, though, and the reagents required for exome sequencing are getting more affordable, he noted.

The GIFT EXOME study was supported by Bristol-Myers Squibb/Sanofi. Dr. Price reported serving as a consultant to those companies and more than half a dozen others. He also holds an equity interest in Iverson Genetics.

CHICAGO – Implantation of a dual-chamber pacemaker effectively reduced fainting episodes in carefully selected patients with neurally mediated syncope, according to the findings of the International Study on Syncope of Uncertain Etiology-3.

"We think that after ISSUE-3, the efficacy of pacing is established and that no other randomized trials will be performed in this field to replicate the results," Dr. Michele Brignole, director of cardiology at Hospital del Tigullio in Lavagna, Italy, declared at the annual meeting of the American College of Cardiology.

Photo:Bruce Jancin/IMNG Medical Media

ISSUE-3 was a randomized, double-blind, prospective clinical trial conducted in Europe and Canada. The study tested a specific management strategy for neurally mediated syncope (NMS) that relied upon placement of an implantable loop recorder (ILD) to document asystole as the cause of a syncopal event. Only patients with ILD documentation of a lengthy asystole were eligible to receive a pacemaker, and even then, only if they met additional clinical criteria.

Two prior clinical trials failed to show benefit for pacemaker implantation in patients with NMS. ISSUE-3 succeeded where the others failed for two reasons, in Dr. Brignole’s view: the strategy of documenting a syncopal episode with an ILD, and careful patient selection. The prior studies put pacemakers in unselected patients with NMS.

"I strongly recommend not putting in a pacemaker without documentation of the syncopal mechanism as asystole. If you don’t put in an ILD you’ll come back to the negative result of the other trials," the electrophysiologist said.

In ISSUE-3, 77 patients received a dual-chamber pacemaker and were randomized in double-blind fashion to pacemaker on or off. The primary endpoint was the occurrence of a first syncopal event during 2 years of follow-up. The rate was 25% in the pacemaker-on group, compared with 57% among those with the pacemaker off. The observed 32% absolute reduction in syncope and 57% relative reduction in syncope with pacemaker therapy were highly significant, he said.

The clinical criteria employed to define the population benefiting from pacemaker therapy included older age: Participants had to be more than 40 years old, since younger patients with NMS often experience a prodrome that enables them to head off fainting episodes through physical counter-pressure maneuvers. Indeed, the ISSUE-3 population averaged 63 years of age, with an 8-year history of NMS.

Study participants also had to have severe syncope that adversely affected their quality of life, with three or more episodes in the 2 years prior to enrollment. Most patients lacked premonitory symptoms, thus exposing them to a high risk of injury from falls. Other diseases, including carotid disease and aortic disease, were carefully ruled out.

During the screening phase of the study, 511 patients received an ILD. During up to 2 years of follow-up, an ECG-documented syncopal event occurred in 158 patients – 56% of the events were the result of asystole. Patients with syncope involving asystole lasting longer than 3 seconds or with nonsyncopal asystole for longer than 6 seconds were eligible for pacemaker implantation. The average length of asystole in study participants was 11 seconds.

Based upon this and earlier studies, Dr. Brignole estimated that 9% of patients with NMS meet the ISSUE-3 criteria for an ILD. Roughly 18% of ILD recipients would qualify for pacemaker therapy within 1 year, and 40% would qualify within 4 years.

In this select group, the number needed to treat with a pacemaker to avoid one syncopal episode in 2 years is three, he added.

Noting that one-quarter of ISSUE-3 participants experienced a syncopal event despite having their pacemaker turned on, Dr. Brignole said that the next step in the study will be a subgroup analysis to identify those patients most and least likely to benefit from this invasive device therapy.

The ISSUE-3 trial was funded by Medtronic. Dr. Brignole reported having no financial conflicts.

CHICAGO – Implantation of a dual-chamber pacemaker effectively reduced fainting episodes in carefully selected patients with neurally mediated syncope, according to the findings of the International Study on Syncope of Uncertain Etiology-3.

"We think that after ISSUE-3, the efficacy of pacing is established and that no other randomized trials will be performed in this field to replicate the results," Dr. Michele Brignole, director of cardiology at Hospital del Tigullio in Lavagna, Italy, declared at the annual meeting of the American College of Cardiology.

Photo:Bruce Jancin/IMNG Medical Media

ISSUE-3 was a randomized, double-blind, prospective clinical trial conducted in Europe and Canada. The study tested a specific management strategy for neurally mediated syncope (NMS) that relied upon placement of an implantable loop recorder (ILD) to document asystole as the cause of a syncopal event. Only patients with ILD documentation of a lengthy asystole were eligible to receive a pacemaker, and even then, only if they met additional clinical criteria.

Two prior clinical trials failed to show benefit for pacemaker implantation in patients with NMS. ISSUE-3 succeeded where the others failed for two reasons, in Dr. Brignole’s view: the strategy of documenting a syncopal episode with an ILD, and careful patient selection. The prior studies put pacemakers in unselected patients with NMS.

"I strongly recommend not putting in a pacemaker without documentation of the syncopal mechanism as asystole. If you don’t put in an ILD you’ll come back to the negative result of the other trials," the electrophysiologist said.

In ISSUE-3, 77 patients received a dual-chamber pacemaker and were randomized in double-blind fashion to pacemaker on or off. The primary endpoint was the occurrence of a first syncopal event during 2 years of follow-up. The rate was 25% in the pacemaker-on group, compared with 57% among those with the pacemaker off. The observed 32% absolute reduction in syncope and 57% relative reduction in syncope with pacemaker therapy were highly significant, he said.

The clinical criteria employed to define the population benefiting from pacemaker therapy included older age: Participants had to be more than 40 years old, since younger patients with NMS often experience a prodrome that enables them to head off fainting episodes through physical counter-pressure maneuvers. Indeed, the ISSUE-3 population averaged 63 years of age, with an 8-year history of NMS.

Study participants also had to have severe syncope that adversely affected their quality of life, with three or more episodes in the 2 years prior to enrollment. Most patients lacked premonitory symptoms, thus exposing them to a high risk of injury from falls. Other diseases, including carotid disease and aortic disease, were carefully ruled out.

During the screening phase of the study, 511 patients received an ILD. During up to 2 years of follow-up, an ECG-documented syncopal event occurred in 158 patients – 56% of the events were the result of asystole. Patients with syncope involving asystole lasting longer than 3 seconds or with nonsyncopal asystole for longer than 6 seconds were eligible for pacemaker implantation. The average length of asystole in study participants was 11 seconds.

Based upon this and earlier studies, Dr. Brignole estimated that 9% of patients with NMS meet the ISSUE-3 criteria for an ILD. Roughly 18% of ILD recipients would qualify for pacemaker therapy within 1 year, and 40% would qualify within 4 years.

In this select group, the number needed to treat with a pacemaker to avoid one syncopal episode in 2 years is three, he added.

Noting that one-quarter of ISSUE-3 participants experienced a syncopal event despite having their pacemaker turned on, Dr. Brignole said that the next step in the study will be a subgroup analysis to identify those patients most and least likely to benefit from this invasive device therapy.

The ISSUE-3 trial was funded by Medtronic. Dr. Brignole reported having no financial conflicts.

CHICAGO – Implantation of a dual-chamber pacemaker effectively reduced fainting episodes in carefully selected patients with neurally mediated syncope, according to the findings of the International Study on Syncope of Uncertain Etiology-3.

"We think that after ISSUE-3, the efficacy of pacing is established and that no other randomized trials will be performed in this field to replicate the results," Dr. Michele Brignole, director of cardiology at Hospital del Tigullio in Lavagna, Italy, declared at the annual meeting of the American College of Cardiology.

Photo:Bruce Jancin/IMNG Medical Media

ISSUE-3 was a randomized, double-blind, prospective clinical trial conducted in Europe and Canada. The study tested a specific management strategy for neurally mediated syncope (NMS) that relied upon placement of an implantable loop recorder (ILD) to document asystole as the cause of a syncopal event. Only patients with ILD documentation of a lengthy asystole were eligible to receive a pacemaker, and even then, only if they met additional clinical criteria.

Two prior clinical trials failed to show benefit for pacemaker implantation in patients with NMS. ISSUE-3 succeeded where the others failed for two reasons, in Dr. Brignole’s view: the strategy of documenting a syncopal episode with an ILD, and careful patient selection. The prior studies put pacemakers in unselected patients with NMS.

"I strongly recommend not putting in a pacemaker without documentation of the syncopal mechanism as asystole. If you don’t put in an ILD you’ll come back to the negative result of the other trials," the electrophysiologist said.

In ISSUE-3, 77 patients received a dual-chamber pacemaker and were randomized in double-blind fashion to pacemaker on or off. The primary endpoint was the occurrence of a first syncopal event during 2 years of follow-up. The rate was 25% in the pacemaker-on group, compared with 57% among those with the pacemaker off. The observed 32% absolute reduction in syncope and 57% relative reduction in syncope with pacemaker therapy were highly significant, he said.

The clinical criteria employed to define the population benefiting from pacemaker therapy included older age: Participants had to be more than 40 years old, since younger patients with NMS often experience a prodrome that enables them to head off fainting episodes through physical counter-pressure maneuvers. Indeed, the ISSUE-3 population averaged 63 years of age, with an 8-year history of NMS.

Study participants also had to have severe syncope that adversely affected their quality of life, with three or more episodes in the 2 years prior to enrollment. Most patients lacked premonitory symptoms, thus exposing them to a high risk of injury from falls. Other diseases, including carotid disease and aortic disease, were carefully ruled out.

During the screening phase of the study, 511 patients received an ILD. During up to 2 years of follow-up, an ECG-documented syncopal event occurred in 158 patients – 56% of the events were the result of asystole. Patients with syncope involving asystole lasting longer than 3 seconds or with nonsyncopal asystole for longer than 6 seconds were eligible for pacemaker implantation. The average length of asystole in study participants was 11 seconds.

Based upon this and earlier studies, Dr. Brignole estimated that 9% of patients with NMS meet the ISSUE-3 criteria for an ILD. Roughly 18% of ILD recipients would qualify for pacemaker therapy within 1 year, and 40% would qualify within 4 years.

In this select group, the number needed to treat with a pacemaker to avoid one syncopal episode in 2 years is three, he added.

Noting that one-quarter of ISSUE-3 participants experienced a syncopal event despite having their pacemaker turned on, Dr. Brignole said that the next step in the study will be a subgroup analysis to identify those patients most and least likely to benefit from this invasive device therapy.

The ISSUE-3 trial was funded by Medtronic. Dr. Brignole reported having no financial conflicts.

WAIKOLOA, HAWAII – Topical clindamycin 1.2%/benzoyl peroxide 2.5% gel proved markedly less irritating than adapalene 0.1%/benzoyl peroxide 2.5% gel in an observer-blinded, split-face acne treatment study.

Twenty-one acne patients applied clindamycin 1%/benzoyl peroxide 2.5% gel (Acanya Gel, Valeant) to one side of their face and adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo Gel, Galderma) to the other side once daily for 14 days.

On day 14, 86% of patients reported mild to no redness on the Acanya-treated side of their face. In contrast, 62% of patients rated their Epiduo-treated side as having mild to no erythema, according to Dr. William Ting, a dermatologist in San Ramon, Calif.

One patient dropped out of the study because of severe erythema on the Epiduo-treated side of their face on day 5, another stopped the combination gel on day 9, and two more patients reported severe erythema on their Epiduo-treated side on day 14. In contrast, no one developed severe erythema on the Acanya-treated half of the face. Blinded investigator clinical assessment of dryness and erythema was scored on a 0-3 scale, with 0 signaling none and 3 severe. Mean erythema scores worsened from baseline value of 0.2 by 0.7 points at 14 days on the Acanya-treated side, and by a significantly greater 1.3 points on the Epiduo side. Dryness increased by a mean 0.4 points on the Acanya side and by 1.0 points with Epiduo.

Dr. Ting observed that both of the topical benzoyl peroxide fixed combination products have previously demonstrated comparable efficacy in separate large clinical trials for treatment of both inflammatory and noninflammatory lesions in patients with moderate acne. But it’s reasonable to assume that the reduced irritation potential with Acanya is likely to translate into better treatment adherence, he noted at the seminar sponsored by the Skin Disease Education Foundation (SDEF).

"The study findings suggest that dermatologists may not have to sacrifice efficacy for tolerability when it comes to topical acne therapy. For patients with sensitive skin where benzoyl peroxide is helpful, Acanya may be an excellent consideration," he said in an interview.

Dr. Ting reported that he serves on the advisory board for Valeant, which markets Acanya.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Topical clindamycin 1.2%/benzoyl peroxide 2.5% gel proved markedly less irritating than adapalene 0.1%/benzoyl peroxide 2.5% gel in an observer-blinded, split-face acne treatment study.

Twenty-one acne patients applied clindamycin 1%/benzoyl peroxide 2.5% gel (Acanya Gel, Valeant) to one side of their face and adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo Gel, Galderma) to the other side once daily for 14 days.

On day 14, 86% of patients reported mild to no redness on the Acanya-treated side of their face. In contrast, 62% of patients rated their Epiduo-treated side as having mild to no erythema, according to Dr. William Ting, a dermatologist in San Ramon, Calif.

One patient dropped out of the study because of severe erythema on the Epiduo-treated side of their face on day 5, another stopped the combination gel on day 9, and two more patients reported severe erythema on their Epiduo-treated side on day 14. In contrast, no one developed severe erythema on the Acanya-treated half of the face. Blinded investigator clinical assessment of dryness and erythema was scored on a 0-3 scale, with 0 signaling none and 3 severe. Mean erythema scores worsened from baseline value of 0.2 by 0.7 points at 14 days on the Acanya-treated side, and by a significantly greater 1.3 points on the Epiduo side. Dryness increased by a mean 0.4 points on the Acanya side and by 1.0 points with Epiduo.

Dr. Ting observed that both of the topical benzoyl peroxide fixed combination products have previously demonstrated comparable efficacy in separate large clinical trials for treatment of both inflammatory and noninflammatory lesions in patients with moderate acne. But it’s reasonable to assume that the reduced irritation potential with Acanya is likely to translate into better treatment adherence, he noted at the seminar sponsored by the Skin Disease Education Foundation (SDEF).

"The study findings suggest that dermatologists may not have to sacrifice efficacy for tolerability when it comes to topical acne therapy. For patients with sensitive skin where benzoyl peroxide is helpful, Acanya may be an excellent consideration," he said in an interview.

Dr. Ting reported that he serves on the advisory board for Valeant, which markets Acanya.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Topical clindamycin 1.2%/benzoyl peroxide 2.5% gel proved markedly less irritating than adapalene 0.1%/benzoyl peroxide 2.5% gel in an observer-blinded, split-face acne treatment study.

Twenty-one acne patients applied clindamycin 1%/benzoyl peroxide 2.5% gel (Acanya Gel, Valeant) to one side of their face and adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo Gel, Galderma) to the other side once daily for 14 days.

On day 14, 86% of patients reported mild to no redness on the Acanya-treated side of their face. In contrast, 62% of patients rated their Epiduo-treated side as having mild to no erythema, according to Dr. William Ting, a dermatologist in San Ramon, Calif.

One patient dropped out of the study because of severe erythema on the Epiduo-treated side of their face on day 5, another stopped the combination gel on day 9, and two more patients reported severe erythema on their Epiduo-treated side on day 14. In contrast, no one developed severe erythema on the Acanya-treated half of the face. Blinded investigator clinical assessment of dryness and erythema was scored on a 0-3 scale, with 0 signaling none and 3 severe. Mean erythema scores worsened from baseline value of 0.2 by 0.7 points at 14 days on the Acanya-treated side, and by a significantly greater 1.3 points on the Epiduo side. Dryness increased by a mean 0.4 points on the Acanya side and by 1.0 points with Epiduo.

Dr. Ting observed that both of the topical benzoyl peroxide fixed combination products have previously demonstrated comparable efficacy in separate large clinical trials for treatment of both inflammatory and noninflammatory lesions in patients with moderate acne. But it’s reasonable to assume that the reduced irritation potential with Acanya is likely to translate into better treatment adherence, he noted at the seminar sponsored by the Skin Disease Education Foundation (SDEF).

"The study findings suggest that dermatologists may not have to sacrifice efficacy for tolerability when it comes to topical acne therapy. For patients with sensitive skin where benzoyl peroxide is helpful, Acanya may be an excellent consideration," he said in an interview.

Dr. Ting reported that he serves on the advisory board for Valeant, which markets Acanya.

SDEF and this news organization are owned by Elsevier.

CHICAGO – Selective renal denervation for the treatment of resistant hypertension continues to rack up impressively large and durable blood pressure reductions and a solid safety profile 3 years post-procedure, according to the latest update from the Symplicity HTN-1 study, an open-label, uncontrolled investigation.

At baseline the 153 participants in the study conducted in Australia, the United States, and Europe had a mean office blood pressure of 175/98 mm Hg, despite being on an average of 5.1 antihypertensive medications. At 36 months post-denervation they maintained an average in-office blood pressure reduction of -33/-19 mm Hg, according to Dr. Paul A. Sobotka, professor of medicine at Ohio State University, Columbus.

Bruce Jancin/IMNG Medical Media

The response rate rose over time. One month post-denervation, 31% of HTN-1 participants were nonresponders as defined by failure to reduce their office systolic blood pressure by at least 10 mm Hg compared to baseline. By 1 year follow-up, the nonresponder rate had fallen to 21%. At 2 years, it was 10%. And at 36 months it was zero.

In other words, the response rate climbed from 69% at 1 month to 100% at 3 years. Thus, it would be premature to repeat renal denervation or switch to alternative therapy because of blood pressure nonresponse at 6 months, the cardiologist said.

"The assumption had been that nonresponse represented inadequate treatment related either to the device or to the operator. That would not appear to be the case at this time. I assume that the nonresponder rate is primarily related to a patient-based characteristic. But so far, we can identify no patient characteristic or drug characteristic that predicts early nonresponse and later response. It’s a wonderful area to look into further," he continued.

The blood pressure reduction was similar regardless of patient age, diabetes status, or baseline renal function.

"What’s particularly gratifying to me is that elderly patients seem to have a significant reduction in systolic blood pressure and narrowing of pulse pressure. To the extent that [elevations of these parameters] are risk factors for the development of cerebrovascular disease, this therapy may have particular value in the elderly population," Dr. Sobotka noted.

With regard to long-term safety, there have been no hypotensive events requiring hospitalization and no change over time in mean electrolyte levels or estimated glomerular filtration rate.

"The absence of a significant reduction in eGFR in the presence of a 30 mm Hg decrease in systolic blood pressure is virtually unheralded in hypertension therapy. One would have expected that the reduction in blood pressure should have been accompanied by a significant reduction in eGFR, which was not seen. The eGFR looks to be stable over 3 years," Dr. Sobotka observed.

Bilateral selective renal denervation is a minimally invasive endovascular procedure targeting the sympathetic nerves running to and from the kidney. It is made possible by the fact that the renal afferent and efferent sympathetic nerves are located in the adventitia of the renal artery wall, well within reach of radiofrequency energy delivered by a special catheter.

Chronic activation of renal sympathetic outflow is a prominent feature in untreated essential hypertension. Animal studies have demonstrated that severing the renal sympathetic nerves reverses or prevents hypertension.

An estimated 15%-20% of patients diagnosed with hypertension are classified as having treatment-resistant hypertension as defined by a systolic blood pressure of at least 160 mm Hg despite three or more antihypertensive drugs.

The mean procedure time was 38 minutes, with an average of four radiofrequency ablations per artery delivered by the proprietary Medtronic Symplicity renal denervation system. Intravenous narcotics and sedatives were used for pain during ablation. Minor complications occurred in 4 of 153 patients. These consisted of three minor access site complications and one renal artery dissection that occurred prior to ablation and was stented with no further consequences.

In response to audience questions about the possibility of nerve sprouting eventually limiting the effectiveness of renal denervation, Dr. Sobotka said that studies in kidney transplant recipients indicate that while there is some regrowth of efferent fibers with partial neurologic activity, the outbound afferent fibers have little or no ability to reconnect.

"We haven’t reexamined neurologic function of the kidneys post-denervation. That needs to be looked at. But to give a pedestrian response, I’d say the blood pressure response is so significant that it’s hard to imagine that something at a neurologic level has regrown that has any clinical importance," the cardiologist explained.

The Symplicity HTN-1 study was an open-label and uncontrolled. In contrast, the Simplicity HTN-2 study features a randomized prospective crossover design. The 6-month results of HTN-2 have been published (Lancet 2010;376:1903-9). At the Chicago ACC meeting, HTN-2 chief investigator Dr. Murray Esler presented the 1-year findings, focusing on the 35 control subjects who crossed over to renal denervation after 6 months of usual care.

The control subjects had a baseline blood pressure of 178/98 mm Hg despite being on an average of five antihypertensive drugs. After 6 months of usual care, their blood pressure had increased to 190/100 mm Hg. But 6 months after undergoing the ablation procedure, their average office blood pressure was 166/92 mm Hg.

One patient was hospitalized for post-procedure hypotension. This individual was treated with intravenous fluids and a reduction in antihypertensive medication and was discharged without further incident. Such occurrences have been quite rare among the roughly 4,000 patients treated worldwide to date, according to Dr. Esler, associated director of the Baker IDI Heart and Diabetes Institute, Melbourne.

Two patients in the control arm had a total of three hypertensive episodes requiring hospitalization during the 6-month usual care phase prior to crossover to renal denervation.

"These patients, of course, ended up as very good treatment responders," he said.

These severe hypertensive episodes while on usual care, along with the natural tendency of blood pressure to rise from baseline to crossover in the control group despite medication, underscore the potential costs in delaying renal denervation, Dr. Esler commented.

A pivotal Phase-3 Symplicity HTN-3 trial is underway in the United States, where renal denervation remains investigational. The study, led by Dr. George Bakris, president of the American Society of Hypertension and professor of medicine at the University of Chicago, involves more than 500 patients with resistant hypertension. It features a blinded crossover study design. The Symplicity system is commercially available in Australia, Europe, and Asia.

Dr. Sobotka is a paid advisor to Medtronic. Dr. Esler has received research grants from and is a paid consultant to Medtronic and Ardian.

CHICAGO – Selective renal denervation for the treatment of resistant hypertension continues to rack up impressively large and durable blood pressure reductions and a solid safety profile 3 years post-procedure, according to the latest update from the Symplicity HTN-1 study, an open-label, uncontrolled investigation.

At baseline the 153 participants in the study conducted in Australia, the United States, and Europe had a mean office blood pressure of 175/98 mm Hg, despite being on an average of 5.1 antihypertensive medications. At 36 months post-denervation they maintained an average in-office blood pressure reduction of -33/-19 mm Hg, according to Dr. Paul A. Sobotka, professor of medicine at Ohio State University, Columbus.

Bruce Jancin/IMNG Medical Media

The response rate rose over time. One month post-denervation, 31% of HTN-1 participants were nonresponders as defined by failure to reduce their office systolic blood pressure by at least 10 mm Hg compared to baseline. By 1 year follow-up, the nonresponder rate had fallen to 21%. At 2 years, it was 10%. And at 36 months it was zero.

In other words, the response rate climbed from 69% at 1 month to 100% at 3 years. Thus, it would be premature to repeat renal denervation or switch to alternative therapy because of blood pressure nonresponse at 6 months, the cardiologist said.

"The assumption had been that nonresponse represented inadequate treatment related either to the device or to the operator. That would not appear to be the case at this time. I assume that the nonresponder rate is primarily related to a patient-based characteristic. But so far, we can identify no patient characteristic or drug characteristic that predicts early nonresponse and later response. It’s a wonderful area to look into further," he continued.

The blood pressure reduction was similar regardless of patient age, diabetes status, or baseline renal function.

"What’s particularly gratifying to me is that elderly patients seem to have a significant reduction in systolic blood pressure and narrowing of pulse pressure. To the extent that [elevations of these parameters] are risk factors for the development of cerebrovascular disease, this therapy may have particular value in the elderly population," Dr. Sobotka noted.

With regard to long-term safety, there have been no hypotensive events requiring hospitalization and no change over time in mean electrolyte levels or estimated glomerular filtration rate.

"The absence of a significant reduction in eGFR in the presence of a 30 mm Hg decrease in systolic blood pressure is virtually unheralded in hypertension therapy. One would have expected that the reduction in blood pressure should have been accompanied by a significant reduction in eGFR, which was not seen. The eGFR looks to be stable over 3 years," Dr. Sobotka observed.

Bilateral selective renal denervation is a minimally invasive endovascular procedure targeting the sympathetic nerves running to and from the kidney. It is made possible by the fact that the renal afferent and efferent sympathetic nerves are located in the adventitia of the renal artery wall, well within reach of radiofrequency energy delivered by a special catheter.

Chronic activation of renal sympathetic outflow is a prominent feature in untreated essential hypertension. Animal studies have demonstrated that severing the renal sympathetic nerves reverses or prevents hypertension.

An estimated 15%-20% of patients diagnosed with hypertension are classified as having treatment-resistant hypertension as defined by a systolic blood pressure of at least 160 mm Hg despite three or more antihypertensive drugs.

The mean procedure time was 38 minutes, with an average of four radiofrequency ablations per artery delivered by the proprietary Medtronic Symplicity renal denervation system. Intravenous narcotics and sedatives were used for pain during ablation. Minor complications occurred in 4 of 153 patients. These consisted of three minor access site complications and one renal artery dissection that occurred prior to ablation and was stented with no further consequences.

In response to audience questions about the possibility of nerve sprouting eventually limiting the effectiveness of renal denervation, Dr. Sobotka said that studies in kidney transplant recipients indicate that while there is some regrowth of efferent fibers with partial neurologic activity, the outbound afferent fibers have little or no ability to reconnect.

"We haven’t reexamined neurologic function of the kidneys post-denervation. That needs to be looked at. But to give a pedestrian response, I’d say the blood pressure response is so significant that it’s hard to imagine that something at a neurologic level has regrown that has any clinical importance," the cardiologist explained.

The Symplicity HTN-1 study was an open-label and uncontrolled. In contrast, the Simplicity HTN-2 study features a randomized prospective crossover design. The 6-month results of HTN-2 have been published (Lancet 2010;376:1903-9). At the Chicago ACC meeting, HTN-2 chief investigator Dr. Murray Esler presented the 1-year findings, focusing on the 35 control subjects who crossed over to renal denervation after 6 months of usual care.

The control subjects had a baseline blood pressure of 178/98 mm Hg despite being on an average of five antihypertensive drugs. After 6 months of usual care, their blood pressure had increased to 190/100 mm Hg. But 6 months after undergoing the ablation procedure, their average office blood pressure was 166/92 mm Hg.

One patient was hospitalized for post-procedure hypotension. This individual was treated with intravenous fluids and a reduction in antihypertensive medication and was discharged without further incident. Such occurrences have been quite rare among the roughly 4,000 patients treated worldwide to date, according to Dr. Esler, associated director of the Baker IDI Heart and Diabetes Institute, Melbourne.

Two patients in the control arm had a total of three hypertensive episodes requiring hospitalization during the 6-month usual care phase prior to crossover to renal denervation.

"These patients, of course, ended up as very good treatment responders," he said.

These severe hypertensive episodes while on usual care, along with the natural tendency of blood pressure to rise from baseline to crossover in the control group despite medication, underscore the potential costs in delaying renal denervation, Dr. Esler commented.

A pivotal Phase-3 Symplicity HTN-3 trial is underway in the United States, where renal denervation remains investigational. The study, led by Dr. George Bakris, president of the American Society of Hypertension and professor of medicine at the University of Chicago, involves more than 500 patients with resistant hypertension. It features a blinded crossover study design. The Symplicity system is commercially available in Australia, Europe, and Asia.

Dr. Sobotka is a paid advisor to Medtronic. Dr. Esler has received research grants from and is a paid consultant to Medtronic and Ardian.

CHICAGO – Selective renal denervation for the treatment of resistant hypertension continues to rack up impressively large and durable blood pressure reductions and a solid safety profile 3 years post-procedure, according to the latest update from the Symplicity HTN-1 study, an open-label, uncontrolled investigation.

At baseline the 153 participants in the study conducted in Australia, the United States, and Europe had a mean office blood pressure of 175/98 mm Hg, despite being on an average of 5.1 antihypertensive medications. At 36 months post-denervation they maintained an average in-office blood pressure reduction of -33/-19 mm Hg, according to Dr. Paul A. Sobotka, professor of medicine at Ohio State University, Columbus.

Bruce Jancin/IMNG Medical Media

The response rate rose over time. One month post-denervation, 31% of HTN-1 participants were nonresponders as defined by failure to reduce their office systolic blood pressure by at least 10 mm Hg compared to baseline. By 1 year follow-up, the nonresponder rate had fallen to 21%. At 2 years, it was 10%. And at 36 months it was zero.

In other words, the response rate climbed from 69% at 1 month to 100% at 3 years. Thus, it would be premature to repeat renal denervation or switch to alternative therapy because of blood pressure nonresponse at 6 months, the cardiologist said.

"The assumption had been that nonresponse represented inadequate treatment related either to the device or to the operator. That would not appear to be the case at this time. I assume that the nonresponder rate is primarily related to a patient-based characteristic. But so far, we can identify no patient characteristic or drug characteristic that predicts early nonresponse and later response. It’s a wonderful area to look into further," he continued.

The blood pressure reduction was similar regardless of patient age, diabetes status, or baseline renal function.

"What’s particularly gratifying to me is that elderly patients seem to have a significant reduction in systolic blood pressure and narrowing of pulse pressure. To the extent that [elevations of these parameters] are risk factors for the development of cerebrovascular disease, this therapy may have particular value in the elderly population," Dr. Sobotka noted.

With regard to long-term safety, there have been no hypotensive events requiring hospitalization and no change over time in mean electrolyte levels or estimated glomerular filtration rate.

"The absence of a significant reduction in eGFR in the presence of a 30 mm Hg decrease in systolic blood pressure is virtually unheralded in hypertension therapy. One would have expected that the reduction in blood pressure should have been accompanied by a significant reduction in eGFR, which was not seen. The eGFR looks to be stable over 3 years," Dr. Sobotka observed.

Bilateral selective renal denervation is a minimally invasive endovascular procedure targeting the sympathetic nerves running to and from the kidney. It is made possible by the fact that the renal afferent and efferent sympathetic nerves are located in the adventitia of the renal artery wall, well within reach of radiofrequency energy delivered by a special catheter.

Chronic activation of renal sympathetic outflow is a prominent feature in untreated essential hypertension. Animal studies have demonstrated that severing the renal sympathetic nerves reverses or prevents hypertension.

An estimated 15%-20% of patients diagnosed with hypertension are classified as having treatment-resistant hypertension as defined by a systolic blood pressure of at least 160 mm Hg despite three or more antihypertensive drugs.

The mean procedure time was 38 minutes, with an average of four radiofrequency ablations per artery delivered by the proprietary Medtronic Symplicity renal denervation system. Intravenous narcotics and sedatives were used for pain during ablation. Minor complications occurred in 4 of 153 patients. These consisted of three minor access site complications and one renal artery dissection that occurred prior to ablation and was stented with no further consequences.

In response to audience questions about the possibility of nerve sprouting eventually limiting the effectiveness of renal denervation, Dr. Sobotka said that studies in kidney transplant recipients indicate that while there is some regrowth of efferent fibers with partial neurologic activity, the outbound afferent fibers have little or no ability to reconnect.

"We haven’t reexamined neurologic function of the kidneys post-denervation. That needs to be looked at. But to give a pedestrian response, I’d say the blood pressure response is so significant that it’s hard to imagine that something at a neurologic level has regrown that has any clinical importance," the cardiologist explained.

The Symplicity HTN-1 study was an open-label and uncontrolled. In contrast, the Simplicity HTN-2 study features a randomized prospective crossover design. The 6-month results of HTN-2 have been published (Lancet 2010;376:1903-9). At the Chicago ACC meeting, HTN-2 chief investigator Dr. Murray Esler presented the 1-year findings, focusing on the 35 control subjects who crossed over to renal denervation after 6 months of usual care.

The control subjects had a baseline blood pressure of 178/98 mm Hg despite being on an average of five antihypertensive drugs. After 6 months of usual care, their blood pressure had increased to 190/100 mm Hg. But 6 months after undergoing the ablation procedure, their average office blood pressure was 166/92 mm Hg.

One patient was hospitalized for post-procedure hypotension. This individual was treated with intravenous fluids and a reduction in antihypertensive medication and was discharged without further incident. Such occurrences have been quite rare among the roughly 4,000 patients treated worldwide to date, according to Dr. Esler, associated director of the Baker IDI Heart and Diabetes Institute, Melbourne.

Two patients in the control arm had a total of three hypertensive episodes requiring hospitalization during the 6-month usual care phase prior to crossover to renal denervation.

"These patients, of course, ended up as very good treatment responders," he said.

These severe hypertensive episodes while on usual care, along with the natural tendency of blood pressure to rise from baseline to crossover in the control group despite medication, underscore the potential costs in delaying renal denervation, Dr. Esler commented.

A pivotal Phase-3 Symplicity HTN-3 trial is underway in the United States, where renal denervation remains investigational. The study, led by Dr. George Bakris, president of the American Society of Hypertension and professor of medicine at the University of Chicago, involves more than 500 patients with resistant hypertension. It features a blinded crossover study design. The Symplicity system is commercially available in Australia, Europe, and Asia.

Dr. Sobotka is a paid advisor to Medtronic. Dr. Esler has received research grants from and is a paid consultant to Medtronic and Ardian.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

CHICAGO – The rate of increase in systolic blood pressure during an adult’s 30s, 40s, and 50s is a stronger predictor of later structural heart damage than is their absolute blood pressure.

This finding from the longest-running birth cohort study in the United Kingdom – now entering its 66th year of follow-up – has major implications for how high blood pressure is approached, according to Dr. Arjun K. Ghosh, a cardiologist at the National Heart and Lung Institute, Imperial College London.

"At the moment, if patients don’t reach that certain magic level of high blood pressure, they’re often not treated. They’re asked to come back, and a watch-and-wait policy is instituted," he noted at the annual meeting of the American College of Cardiology. "What we found in our study, in measuring people’s blood pressure from their 30s on, was that those with a faster rise in blood pressure had a heavier heart, or increased left ventricular mass, when they were 60-64 years of age. And this was true for any level of blood pressure, high or low. It actually wasn’t how high the blood pressure became as it was how quickly the blood pressure was rising."

A second key finding was that left ventricular hypertrophy was not reversed among hypertensive study participants whose blood pressure was normalized via medication. These patients had a significantly greater left ventricular mass indexed to body surface area (LVMI) as did their peers who had the same normal-range blood pressure but had never been treated for hypertension.

"This policy of watching and waiting for the blood pressure to cross a certain threshold before starting antihypertensive therapy may be waiting too long. The irreversible damage has already been done," Dr. Ghosh continued. "A new approach may be required. We need to identify those individuals whose blood pressure rises the fastest and target them with the most effective treatment."

His analysis involved 1,653 participants who were in the Medical Research Council National Survey of Health and Development and were born in Britain in a single week in March 1946. Subjects were followed serially, and underwent echocardiography and LVMI measurement at age 60-64.

The higher a subject’s systolic blood pressure at age 36, 43, 53, or 60-64, the greater the LVMI at age 60-64.

Moreover, individuals with well controlled blood pressure on antihypertensive therapy at age 60-64 had a mean LVMI that was 8.6 g/m² greater than that of subjects not on treatment. Participants on antihypertensive therapy at age 53 had a mean LVMI that was 7.3 g/m² higher than in those who weren’t, and individuals on treatment at age 43 had a mean LVMI at age 60-64 that was 11.5 g/m² more than in those not on treatment at age 43.

A sharp increase in blood pressure between ages 43 and 53 was particularly detrimental for LV size at age 60-64. An increase of 1 standard deviation in systolic blood pressure during that time period was associated with a 4 g/m² higher LVMI, whereas an increase of 1 standard deviation between ages 36 and 43 was associated with a 1 g/m² increase.

As this was an observational study, a clinical trial needs to be conducted before the findings can be translated into a change in practice. This study would compare the watch-and-wait strategy of threshold-based antihypertensive therapy with this novel approach stressing early identification and treatment of patients with rapidly increased systolic blood pressure, Dr. Ghosh said. Such a study is eminently feasible and could yield results in about 5 years using as the end point change in left ventricular size, which is well-established as a key driver of heart failure.

This new concept that the trajectory at which blood pressure rises has an irreversible adverse impact on cardiac structure is quite plausible, according to Dr. Joanne Foody.

"I think the real kernel is there needs to be more ongoing monitoring, particularly in young adults, so we don’t miss that window," she said in an interview.

The challenge is that young people leave their pediatricians and, except for injuries or acute illnesses, may not see a physician again until they’re in their 40s, observed Dr. Foody, medical director of the cardiovascular wellness program at Brigham and Women’s Hospital, Boston.

"We need to do more for people and do it earlier. People don’t really start thinking about preventive health until they’re in their 40s and 50s," she said.

The study was sponsored by the U.K.’s Medical Research Council. Dr. Ghosh and Dr. Foody reported having no financial conflicts.

CHICAGO – The rate of increase in systolic blood pressure during an adult’s 30s, 40s, and 50s is a stronger predictor of later structural heart damage than is their absolute blood pressure.

This finding from the longest-running birth cohort study in the United Kingdom – now entering its 66th year of follow-up – has major implications for how high blood pressure is approached, according to Dr. Arjun K. Ghosh, a cardiologist at the National Heart and Lung Institute, Imperial College London.

"At the moment, if patients don’t reach that certain magic level of high blood pressure, they’re often not treated. They’re asked to come back, and a watch-and-wait policy is instituted," he noted at the annual meeting of the American College of Cardiology. "What we found in our study, in measuring people’s blood pressure from their 30s on, was that those with a faster rise in blood pressure had a heavier heart, or increased left ventricular mass, when they were 60-64 years of age. And this was true for any level of blood pressure, high or low. It actually wasn’t how high the blood pressure became as it was how quickly the blood pressure was rising."

A second key finding was that left ventricular hypertrophy was not reversed among hypertensive study participants whose blood pressure was normalized via medication. These patients had a significantly greater left ventricular mass indexed to body surface area (LVMI) as did their peers who had the same normal-range blood pressure but had never been treated for hypertension.

"This policy of watching and waiting for the blood pressure to cross a certain threshold before starting antihypertensive therapy may be waiting too long. The irreversible damage has already been done," Dr. Ghosh continued. "A new approach may be required. We need to identify those individuals whose blood pressure rises the fastest and target them with the most effective treatment."

His analysis involved 1,653 participants who were in the Medical Research Council National Survey of Health and Development and were born in Britain in a single week in March 1946. Subjects were followed serially, and underwent echocardiography and LVMI measurement at age 60-64.

The higher a subject’s systolic blood pressure at age 36, 43, 53, or 60-64, the greater the LVMI at age 60-64.

Moreover, individuals with well controlled blood pressure on antihypertensive therapy at age 60-64 had a mean LVMI that was 8.6 g/m² greater than that of subjects not on treatment. Participants on antihypertensive therapy at age 53 had a mean LVMI that was 7.3 g/m² higher than in those who weren’t, and individuals on treatment at age 43 had a mean LVMI at age 60-64 that was 11.5 g/m² more than in those not on treatment at age 43.

A sharp increase in blood pressure between ages 43 and 53 was particularly detrimental for LV size at age 60-64. An increase of 1 standard deviation in systolic blood pressure during that time period was associated with a 4 g/m² higher LVMI, whereas an increase of 1 standard deviation between ages 36 and 43 was associated with a 1 g/m² increase.

As this was an observational study, a clinical trial needs to be conducted before the findings can be translated into a change in practice. This study would compare the watch-and-wait strategy of threshold-based antihypertensive therapy with this novel approach stressing early identification and treatment of patients with rapidly increased systolic blood pressure, Dr. Ghosh said. Such a study is eminently feasible and could yield results in about 5 years using as the end point change in left ventricular size, which is well-established as a key driver of heart failure.

This new concept that the trajectory at which blood pressure rises has an irreversible adverse impact on cardiac structure is quite plausible, according to Dr. Joanne Foody.

"I think the real kernel is there needs to be more ongoing monitoring, particularly in young adults, so we don’t miss that window," she said in an interview.

The challenge is that young people leave their pediatricians and, except for injuries or acute illnesses, may not see a physician again until they’re in their 40s, observed Dr. Foody, medical director of the cardiovascular wellness program at Brigham and Women’s Hospital, Boston.

"We need to do more for people and do it earlier. People don’t really start thinking about preventive health until they’re in their 40s and 50s," she said.

The study was sponsored by the U.K.’s Medical Research Council. Dr. Ghosh and Dr. Foody reported having no financial conflicts.

CHICAGO – The rate of increase in systolic blood pressure during an adult’s 30s, 40s, and 50s is a stronger predictor of later structural heart damage than is their absolute blood pressure.

This finding from the longest-running birth cohort study in the United Kingdom – now entering its 66th year of follow-up – has major implications for how high blood pressure is approached, according to Dr. Arjun K. Ghosh, a cardiologist at the National Heart and Lung Institute, Imperial College London.

"At the moment, if patients don’t reach that certain magic level of high blood pressure, they’re often not treated. They’re asked to come back, and a watch-and-wait policy is instituted," he noted at the annual meeting of the American College of Cardiology. "What we found in our study, in measuring people’s blood pressure from their 30s on, was that those with a faster rise in blood pressure had a heavier heart, or increased left ventricular mass, when they were 60-64 years of age. And this was true for any level of blood pressure, high or low. It actually wasn’t how high the blood pressure became as it was how quickly the blood pressure was rising."

A second key finding was that left ventricular hypertrophy was not reversed among hypertensive study participants whose blood pressure was normalized via medication. These patients had a significantly greater left ventricular mass indexed to body surface area (LVMI) as did their peers who had the same normal-range blood pressure but had never been treated for hypertension.

"This policy of watching and waiting for the blood pressure to cross a certain threshold before starting antihypertensive therapy may be waiting too long. The irreversible damage has already been done," Dr. Ghosh continued. "A new approach may be required. We need to identify those individuals whose blood pressure rises the fastest and target them with the most effective treatment."

His analysis involved 1,653 participants who were in the Medical Research Council National Survey of Health and Development and were born in Britain in a single week in March 1946. Subjects were followed serially, and underwent echocardiography and LVMI measurement at age 60-64.

The higher a subject’s systolic blood pressure at age 36, 43, 53, or 60-64, the greater the LVMI at age 60-64.

Moreover, individuals with well controlled blood pressure on antihypertensive therapy at age 60-64 had a mean LVMI that was 8.6 g/m² greater than that of subjects not on treatment. Participants on antihypertensive therapy at age 53 had a mean LVMI that was 7.3 g/m² higher than in those who weren’t, and individuals on treatment at age 43 had a mean LVMI at age 60-64 that was 11.5 g/m² more than in those not on treatment at age 43.

A sharp increase in blood pressure between ages 43 and 53 was particularly detrimental for LV size at age 60-64. An increase of 1 standard deviation in systolic blood pressure during that time period was associated with a 4 g/m² higher LVMI, whereas an increase of 1 standard deviation between ages 36 and 43 was associated with a 1 g/m² increase.

As this was an observational study, a clinical trial needs to be conducted before the findings can be translated into a change in practice. This study would compare the watch-and-wait strategy of threshold-based antihypertensive therapy with this novel approach stressing early identification and treatment of patients with rapidly increased systolic blood pressure, Dr. Ghosh said. Such a study is eminently feasible and could yield results in about 5 years using as the end point change in left ventricular size, which is well-established as a key driver of heart failure.

This new concept that the trajectory at which blood pressure rises has an irreversible adverse impact on cardiac structure is quite plausible, according to Dr. Joanne Foody.

"I think the real kernel is there needs to be more ongoing monitoring, particularly in young adults, so we don’t miss that window," she said in an interview.

The challenge is that young people leave their pediatricians and, except for injuries or acute illnesses, may not see a physician again until they’re in their 40s, observed Dr. Foody, medical director of the cardiovascular wellness program at Brigham and Women’s Hospital, Boston.

"We need to do more for people and do it earlier. People don’t really start thinking about preventive health until they’re in their 40s and 50s," she said.

The study was sponsored by the U.K.’s Medical Research Council. Dr. Ghosh and Dr. Foody reported having no financial conflicts.

WAIKOLOA, HAWAII – Look for a major cut in reimbursement for the treatment of actinic keratoses when the matter comes up for review by the American Medical Association Relative Value Scale Update Committee in January, according to Dr. Brett M. Coldiron.

"It’s going to be bad, bad. The best-case scenario our team has worked out is a 25% cut," Dr. Coldiron said at the Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

It’s entirely possible that the committee will instead recommend closer to a 50% slash in its report to the Center for Medicare and Medicaid Services, added Dr. Coldiron, who has represented dermatology on the Relative Value Scale Update Committee (RUC) or served in an advisory capacity for the past 19 years.

"That first AK relative value rating was based on numbing [the AK], curetting it twice, electrodesiccation, and [the rating estimated] 47 minutes of nursing time. It’s an extraordinary rating ... [times have changed], and now it’s finally up for review," explained Dr. Coldiron, president of the American College of Mohs Surgery and a 2013 member of the board of directors for the American Academy of Dermatology.

Dermatologists perform 86% of all AK treatments in the United States. And the number of procedures in which they bill Medicare for treating 15 or more AKs jumped by 185% from 1995 to 2006, to nearly 734,000 procedures per year.

Meanwhile, the number of Mohs surgery procedures billed to Medicare has increased by a whopping 400%, skin biopsies by dermatologists have increased by 82%, destructions by 68%, and excisions by 22%.

"Those are extraordinary increases, and you have to realize that they’re underestimates because they don’t include billing under Medicare private plans, which take up about 20% of Medicare dollars," he said.

All the Mohs surgery–related codes will come up for RUC review in April 2013. Dr. Coldiron anticipates reimbursement to be cut by about 20%.

He provided the audience with a colorful behind-the-scenes account of the RUC review process.

"The RUC is the Super Bowl of AMA committees, where everybody sits around a table and tries to strip money away from another specialty," he explained. "The RUC is 26 sharks in a tank with nothing to eat but each other. And we’re a small specialty with a ‘Bite Me’ sign on us. We’re less than 1% of all physicians. We have a seat on RUC because we were there from the beginning. But we have many specialty-specific codes which they can target, and we have rapidly increasing utilization."

What’s it like to stand up for dermatology at a RUC review before adversaries representing 25 other medical specialties? "I present the codes and they shoot questions; they just pound on you, sometimes for days. It’s very uncomfortable. They try to figure out what a code is really worth. It’s not much fun at all," said Dr. Coldiron, a dermatologist at the University of Cincinnati.

This intense battle is fueled by jealousy on the part of other specialties, he said. "Dermatology has done better than anybody else in RUC during the past 20 years. Our share of the Medicare pie has gone from about 2% to 3% of the whole Medicare pool, and they’re all aware of this."

He suspects many of his fellow dermatologists will respond to the coming cut in payment for AK therapy by saying, "Well, I used to bill for 10 AKs when I did 15, now I’m going to bill for all 15 of them." That’s a bad idea, in his view. If utilization suddenly shoots up, reimbursement will simply get cut again. And sharp increases in utilization will attract unwanted attention from the Recovery Audit Contractors (RACs). On a contingency basis, Medicare pays RACS 9%-13% of the money recovered through RAC audits for inappropriate billing.

The anticipated cuts in reimbursement for codes covering AK therapy, Mohs surgery, and medical pathology represent a particularly serious threat to academic dermatology, since most departments derive a substantial portion of their funding from those clinical services. Moreover, academic dermatologists have already been hit harder than others by the loss of consultation codes in the Medicare fee schedule, which translates to an estimated $7,000 per year in lost income for most.

The RUC cuts in reimbursement for AK treatment and Mohs surgery will hurt. But they are by no means the biggest threat facing dermatology, in Dr. Coldiron’s view. That distinction belongs to the Independent Payment Advisory Panel (IPAP) empowered by the Patient Protection and Affordable Care Act. The panel’s job will be to identify overused, overpaid, or useless services and cut Medicare payment rates for providers of those services. Their decisions cannot be reversed except by a two-thirds majority of Congress.

"This is serious for us and all small specialties because anything could happen. Why cover Mohs surgery at all? After all, it’s not covered in Great Britain or France, and they’ve got pretty good health care. Why cover acne – isn’t that cosmetic? Why pay pathologists for seborrheic keratoses? There are all kinds of possibilities here that we need to be prepared for," he cautioned.

He predicted that dermatology and other small specialties will get hit first and hardest by health care cost containment efforts. The RUC doesn’t like dermatology. Nor do Medicare officials and some key members of Congress. Neither does the Medicare Payment Advisory Commission (MedPAC), an independent federal body created to help Congress address complicated health policy issues.

"MedPAC likes primary care. They’re getting a bad attitude after 19 years of no increase for primary care. They want all procedure-oriented specialists to be paid the same as the cognitives," Dr. Coldiron said.

He added that fundamental misconceptions regarding dermatology abound. "They think that what dermatologists do is not important, that it’s cosmetic. And that our increase in Relative Value Units is due to waste, abuse, and minor procedure codes that pay too much. If dermatology disappeared there would be few tears shed," according to Dr. Coldiron.

These critics focus on the fact that dermatology, having reinvented itself as a skin surgical specialty, has become the most procedurally oriented of all specialties. Indeed, in the Medicare database, 73% of dermatologists’ income comes from procedures; ophthalmology is a distant second at 56%.

Dermatology’s critics are unwilling to recognize that the main reason for the big jump in dermatologic procedures during the last 2 decades is the ongoing skin cancer epidemic, Dr. Coldiron continued. He was a coinvestigator in a major study that documented a 75% jump in the age-adjusted rate of skin cancer procedures in the Medicare fee-for-service population between 1992 and 2006 (Arch. Dermatol. 2010;146:283-7).

By 2008, the estimated annual incidence of nonmelanoma skin cancer in the United States stood at nearly 3.7 million cases, far higher than previously recognized (Semin. Cutan. Med. Surg. 2011;30:3-5). Today the incidence is close to 4 million cases per year, he added.

"That’s the result of a lot of baby boomers lying out in the sun. The problem is that the government doesn’t want to pay for it. They would rather pretend it doesn’t exist," Dr. Coldiron concluded.

He reported having no financial conflicts. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Look for a major cut in reimbursement for the treatment of actinic keratoses when the matter comes up for review by the American Medical Association Relative Value Scale Update Committee in January, according to Dr. Brett M. Coldiron.

"It’s going to be bad, bad. The best-case scenario our team has worked out is a 25% cut," Dr. Coldiron said at the Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

It’s entirely possible that the committee will instead recommend closer to a 50% slash in its report to the Center for Medicare and Medicaid Services, added Dr. Coldiron, who has represented dermatology on the Relative Value Scale Update Committee (RUC) or served in an advisory capacity for the past 19 years.

"That first AK relative value rating was based on numbing [the AK], curetting it twice, electrodesiccation, and [the rating estimated] 47 minutes of nursing time. It’s an extraordinary rating ... [times have changed], and now it’s finally up for review," explained Dr. Coldiron, president of the American College of Mohs Surgery and a 2013 member of the board of directors for the American Academy of Dermatology.

Dermatologists perform 86% of all AK treatments in the United States. And the number of procedures in which they bill Medicare for treating 15 or more AKs jumped by 185% from 1995 to 2006, to nearly 734,000 procedures per year.

Meanwhile, the number of Mohs surgery procedures billed to Medicare has increased by a whopping 400%, skin biopsies by dermatologists have increased by 82%, destructions by 68%, and excisions by 22%.

"Those are extraordinary increases, and you have to realize that they’re underestimates because they don’t include billing under Medicare private plans, which take up about 20% of Medicare dollars," he said.

All the Mohs surgery–related codes will come up for RUC review in April 2013. Dr. Coldiron anticipates reimbursement to be cut by about 20%.

He provided the audience with a colorful behind-the-scenes account of the RUC review process.

"The RUC is the Super Bowl of AMA committees, where everybody sits around a table and tries to strip money away from another specialty," he explained. "The RUC is 26 sharks in a tank with nothing to eat but each other. And we’re a small specialty with a ‘Bite Me’ sign on us. We’re less than 1% of all physicians. We have a seat on RUC because we were there from the beginning. But we have many specialty-specific codes which they can target, and we have rapidly increasing utilization."

What’s it like to stand up for dermatology at a RUC review before adversaries representing 25 other medical specialties? "I present the codes and they shoot questions; they just pound on you, sometimes for days. It’s very uncomfortable. They try to figure out what a code is really worth. It’s not much fun at all," said Dr. Coldiron, a dermatologist at the University of Cincinnati.

This intense battle is fueled by jealousy on the part of other specialties, he said. "Dermatology has done better than anybody else in RUC during the past 20 years. Our share of the Medicare pie has gone from about 2% to 3% of the whole Medicare pool, and they’re all aware of this."

He suspects many of his fellow dermatologists will respond to the coming cut in payment for AK therapy by saying, "Well, I used to bill for 10 AKs when I did 15, now I’m going to bill for all 15 of them." That’s a bad idea, in his view. If utilization suddenly shoots up, reimbursement will simply get cut again. And sharp increases in utilization will attract unwanted attention from the Recovery Audit Contractors (RACs). On a contingency basis, Medicare pays RACS 9%-13% of the money recovered through RAC audits for inappropriate billing.

The anticipated cuts in reimbursement for codes covering AK therapy, Mohs surgery, and medical pathology represent a particularly serious threat to academic dermatology, since most departments derive a substantial portion of their funding from those clinical services. Moreover, academic dermatologists have already been hit harder than others by the loss of consultation codes in the Medicare fee schedule, which translates to an estimated $7,000 per year in lost income for most.

The RUC cuts in reimbursement for AK treatment and Mohs surgery will hurt. But they are by no means the biggest threat facing dermatology, in Dr. Coldiron’s view. That distinction belongs to the Independent Payment Advisory Panel (IPAP) empowered by the Patient Protection and Affordable Care Act. The panel’s job will be to identify overused, overpaid, or useless services and cut Medicare payment rates for providers of those services. Their decisions cannot be reversed except by a two-thirds majority of Congress.

"This is serious for us and all small specialties because anything could happen. Why cover Mohs surgery at all? After all, it’s not covered in Great Britain or France, and they’ve got pretty good health care. Why cover acne – isn’t that cosmetic? Why pay pathologists for seborrheic keratoses? There are all kinds of possibilities here that we need to be prepared for," he cautioned.

He predicted that dermatology and other small specialties will get hit first and hardest by health care cost containment efforts. The RUC doesn’t like dermatology. Nor do Medicare officials and some key members of Congress. Neither does the Medicare Payment Advisory Commission (MedPAC), an independent federal body created to help Congress address complicated health policy issues.

"MedPAC likes primary care. They’re getting a bad attitude after 19 years of no increase for primary care. They want all procedure-oriented specialists to be paid the same as the cognitives," Dr. Coldiron said.

He added that fundamental misconceptions regarding dermatology abound. "They think that what dermatologists do is not important, that it’s cosmetic. And that our increase in Relative Value Units is due to waste, abuse, and minor procedure codes that pay too much. If dermatology disappeared there would be few tears shed," according to Dr. Coldiron.

These critics focus on the fact that dermatology, having reinvented itself as a skin surgical specialty, has become the most procedurally oriented of all specialties. Indeed, in the Medicare database, 73% of dermatologists’ income comes from procedures; ophthalmology is a distant second at 56%.

Dermatology’s critics are unwilling to recognize that the main reason for the big jump in dermatologic procedures during the last 2 decades is the ongoing skin cancer epidemic, Dr. Coldiron continued. He was a coinvestigator in a major study that documented a 75% jump in the age-adjusted rate of skin cancer procedures in the Medicare fee-for-service population between 1992 and 2006 (Arch. Dermatol. 2010;146:283-7).

By 2008, the estimated annual incidence of nonmelanoma skin cancer in the United States stood at nearly 3.7 million cases, far higher than previously recognized (Semin. Cutan. Med. Surg. 2011;30:3-5). Today the incidence is close to 4 million cases per year, he added.

"That’s the result of a lot of baby boomers lying out in the sun. The problem is that the government doesn’t want to pay for it. They would rather pretend it doesn’t exist," Dr. Coldiron concluded.

He reported having no financial conflicts. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Look for a major cut in reimbursement for the treatment of actinic keratoses when the matter comes up for review by the American Medical Association Relative Value Scale Update Committee in January, according to Dr. Brett M. Coldiron.

"It’s going to be bad, bad. The best-case scenario our team has worked out is a 25% cut," Dr. Coldiron said at the Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

It’s entirely possible that the committee will instead recommend closer to a 50% slash in its report to the Center for Medicare and Medicaid Services, added Dr. Coldiron, who has represented dermatology on the Relative Value Scale Update Committee (RUC) or served in an advisory capacity for the past 19 years.

"That first AK relative value rating was based on numbing [the AK], curetting it twice, electrodesiccation, and [the rating estimated] 47 minutes of nursing time. It’s an extraordinary rating ... [times have changed], and now it’s finally up for review," explained Dr. Coldiron, president of the American College of Mohs Surgery and a 2013 member of the board of directors for the American Academy of Dermatology.

Dermatologists perform 86% of all AK treatments in the United States. And the number of procedures in which they bill Medicare for treating 15 or more AKs jumped by 185% from 1995 to 2006, to nearly 734,000 procedures per year.

Meanwhile, the number of Mohs surgery procedures billed to Medicare has increased by a whopping 400%, skin biopsies by dermatologists have increased by 82%, destructions by 68%, and excisions by 22%.

"Those are extraordinary increases, and you have to realize that they’re underestimates because they don’t include billing under Medicare private plans, which take up about 20% of Medicare dollars," he said.

All the Mohs surgery–related codes will come up for RUC review in April 2013. Dr. Coldiron anticipates reimbursement to be cut by about 20%.

He provided the audience with a colorful behind-the-scenes account of the RUC review process.

"The RUC is the Super Bowl of AMA committees, where everybody sits around a table and tries to strip money away from another specialty," he explained. "The RUC is 26 sharks in a tank with nothing to eat but each other. And we’re a small specialty with a ‘Bite Me’ sign on us. We’re less than 1% of all physicians. We have a seat on RUC because we were there from the beginning. But we have many specialty-specific codes which they can target, and we have rapidly increasing utilization."

What’s it like to stand up for dermatology at a RUC review before adversaries representing 25 other medical specialties? "I present the codes and they shoot questions; they just pound on you, sometimes for days. It’s very uncomfortable. They try to figure out what a code is really worth. It’s not much fun at all," said Dr. Coldiron, a dermatologist at the University of Cincinnati.

This intense battle is fueled by jealousy on the part of other specialties, he said. "Dermatology has done better than anybody else in RUC during the past 20 years. Our share of the Medicare pie has gone from about 2% to 3% of the whole Medicare pool, and they’re all aware of this."

He suspects many of his fellow dermatologists will respond to the coming cut in payment for AK therapy by saying, "Well, I used to bill for 10 AKs when I did 15, now I’m going to bill for all 15 of them." That’s a bad idea, in his view. If utilization suddenly shoots up, reimbursement will simply get cut again. And sharp increases in utilization will attract unwanted attention from the Recovery Audit Contractors (RACs). On a contingency basis, Medicare pays RACS 9%-13% of the money recovered through RAC audits for inappropriate billing.

The anticipated cuts in reimbursement for codes covering AK therapy, Mohs surgery, and medical pathology represent a particularly serious threat to academic dermatology, since most departments derive a substantial portion of their funding from those clinical services. Moreover, academic dermatologists have already been hit harder than others by the loss of consultation codes in the Medicare fee schedule, which translates to an estimated $7,000 per year in lost income for most.

The RUC cuts in reimbursement for AK treatment and Mohs surgery will hurt. But they are by no means the biggest threat facing dermatology, in Dr. Coldiron’s view. That distinction belongs to the Independent Payment Advisory Panel (IPAP) empowered by the Patient Protection and Affordable Care Act. The panel’s job will be to identify overused, overpaid, or useless services and cut Medicare payment rates for providers of those services. Their decisions cannot be reversed except by a two-thirds majority of Congress.

"This is serious for us and all small specialties because anything could happen. Why cover Mohs surgery at all? After all, it’s not covered in Great Britain or France, and they’ve got pretty good health care. Why cover acne – isn’t that cosmetic? Why pay pathologists for seborrheic keratoses? There are all kinds of possibilities here that we need to be prepared for," he cautioned.

He predicted that dermatology and other small specialties will get hit first and hardest by health care cost containment efforts. The RUC doesn’t like dermatology. Nor do Medicare officials and some key members of Congress. Neither does the Medicare Payment Advisory Commission (MedPAC), an independent federal body created to help Congress address complicated health policy issues.

"MedPAC likes primary care. They’re getting a bad attitude after 19 years of no increase for primary care. They want all procedure-oriented specialists to be paid the same as the cognitives," Dr. Coldiron said.

He added that fundamental misconceptions regarding dermatology abound. "They think that what dermatologists do is not important, that it’s cosmetic. And that our increase in Relative Value Units is due to waste, abuse, and minor procedure codes that pay too much. If dermatology disappeared there would be few tears shed," according to Dr. Coldiron.

These critics focus on the fact that dermatology, having reinvented itself as a skin surgical specialty, has become the most procedurally oriented of all specialties. Indeed, in the Medicare database, 73% of dermatologists’ income comes from procedures; ophthalmology is a distant second at 56%.

Dermatology’s critics are unwilling to recognize that the main reason for the big jump in dermatologic procedures during the last 2 decades is the ongoing skin cancer epidemic, Dr. Coldiron continued. He was a coinvestigator in a major study that documented a 75% jump in the age-adjusted rate of skin cancer procedures in the Medicare fee-for-service population between 1992 and 2006 (Arch. Dermatol. 2010;146:283-7).

By 2008, the estimated annual incidence of nonmelanoma skin cancer in the United States stood at nearly 3.7 million cases, far higher than previously recognized (Semin. Cutan. Med. Surg. 2011;30:3-5). Today the incidence is close to 4 million cases per year, he added.

"That’s the result of a lot of baby boomers lying out in the sun. The problem is that the government doesn’t want to pay for it. They would rather pretend it doesn’t exist," Dr. Coldiron concluded.

He reported having no financial conflicts. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Dr. Brett M. Coldiron is a sort of latter-day Paul Revere, travelling far and wide to spread the alarm to his fellow dermatologists – not of Redcoats a’coming, but of the need to prepare for looming economic hard times.

"I wasn’t invited to speak at your meeting, so I invited myself," he declared by way of introduction at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF), as he launched into an analysis of dermatology’s near-term financial future.

"I’m here to present your 5-year economic plan – what you can expect. I think you can plan your next 5 years based on these predictions. It’s not pretty; and it’s not kind," cautioned Dr. Coldiron, whose expertise regarding health care policy and reform has been forged through long-term involvement representing dermatology on the American Medical Association’s Relative Value Scale Update, Health Care Finance, and Government Health Care Policy committees.

His core message to his colleagues boiled down to this: "Don’t build palaces. It’s time to hunker down."

Dermatology is a heavily procedurally oriented, small specialty – less then 1% of all physicians – which has experienced dramatic growth in procedure volume over the past couple decades. As such, it is a high-priority target for congressional cost-cutting efforts. In the first 4 months of next year, Dr. Coldiron said he expects reimbursement for codes pertaining to actinic keratosis treatment to be cut by 25%-50%, along with a roughly 20% reduction in payment for Mohs surgery. And that’s just the beginning.

Dermatology and other small specialties will bear the brunt of any cost-savings attempts by Congress. Dermatology has powerful enemies in Congress, the Centers for Medicare and Medicaid Services, and the American Medical Association, who view dermatologists as overpaid, wasteful abusers of the system, explained Dr. Coldiron, who is president of the American College of Mohs Surgery and a 2013 member of the American Academy of Dermatology’s board of directors.

Among his predictions for the next 5 years:

• Hospitals and pharmacies, if squeezed too hard, will simply close. Insurers will move into other lines of business coverage. Pharmaceutical companies will reduce their research and development budgets. Thus, reducing physician income will be one of the few politically acceptable health care cost-cutting avenues available.

• There will be more bundling of minor procedures into evaluation and management fees.

• The government will attempt to force all physicians to accept Medicaid. "They’ll probably try to tie it to your acceptance of Medicare. Or maybe they’ll say, ‘We paid for 4 years of postgraduate education; now you owe us 4 years of taking Medicaid,’ " he said.

• The use of physician assistants and nurse practitioners will grow in dermatology. This will result in increased utilization and more intense billing audits along with reimbursement cuts aimed at cancelling out the economic impact of greater utilization.

• Cosmetic procedures and reconstructive surgery will remain safe havens. "They may try to pass a cosmetic procedure tax, but I think the fact that you have another source of income is very important," noted Dr. Coldiron, a dermatologist at the University of Cincinnati.

He recommended that dermatologists temper their income projections for the coming half-decade: "Don’t promise big salaries to new associates, only a percentage of income collected."

Also, read the fine print before jumping on board one of the accountable care organizations that are springing up. "This is government-driven managed care with capitation. What they’re going to do is extract from the specialists and give back to primary care. It’s kind of a loser’s game," he said.

Beyond the next 5 years, however, the outlook for dermatology is bright, Dr. Coldiron stressed.

"Be strong. We are not greedy specialists; we are a frontline specialty fighting an epidemic of skin cancer. We are needed by our patients and by the health care system. The pendulum will eventually swing back our way," he concluded.

Dr. Coldiron reported having no relevant financial conflicts. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Dr. Brett M. Coldiron is a sort of latter-day Paul Revere, travelling far and wide to spread the alarm to his fellow dermatologists – not of Redcoats a’coming, but of the need to prepare for looming economic hard times.

"I wasn’t invited to speak at your meeting, so I invited myself," he declared by way of introduction at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF), as he launched into an analysis of dermatology’s near-term financial future.

"I’m here to present your 5-year economic plan – what you can expect. I think you can plan your next 5 years based on these predictions. It’s not pretty; and it’s not kind," cautioned Dr. Coldiron, whose expertise regarding health care policy and reform has been forged through long-term involvement representing dermatology on the American Medical Association’s Relative Value Scale Update, Health Care Finance, and Government Health Care Policy committees.

His core message to his colleagues boiled down to this: "Don’t build palaces. It’s time to hunker down."

Dermatology is a heavily procedurally oriented, small specialty – less then 1% of all physicians – which has experienced dramatic growth in procedure volume over the past couple decades. As such, it is a high-priority target for congressional cost-cutting efforts. In the first 4 months of next year, Dr. Coldiron said he expects reimbursement for codes pertaining to actinic keratosis treatment to be cut by 25%-50%, along with a roughly 20% reduction in payment for Mohs surgery. And that’s just the beginning.

Dermatology and other small specialties will bear the brunt of any cost-savings attempts by Congress. Dermatology has powerful enemies in Congress, the Centers for Medicare and Medicaid Services, and the American Medical Association, who view dermatologists as overpaid, wasteful abusers of the system, explained Dr. Coldiron, who is president of the American College of Mohs Surgery and a 2013 member of the American Academy of Dermatology’s board of directors.

Among his predictions for the next 5 years:

• Hospitals and pharmacies, if squeezed too hard, will simply close. Insurers will move into other lines of business coverage. Pharmaceutical companies will reduce their research and development budgets. Thus, reducing physician income will be one of the few politically acceptable health care cost-cutting avenues available.

• There will be more bundling of minor procedures into evaluation and management fees.

• The government will attempt to force all physicians to accept Medicaid. "They’ll probably try to tie it to your acceptance of Medicare. Or maybe they’ll say, ‘We paid for 4 years of postgraduate education; now you owe us 4 years of taking Medicaid,’ " he said.

• The use of physician assistants and nurse practitioners will grow in dermatology. This will result in increased utilization and more intense billing audits along with reimbursement cuts aimed at cancelling out the economic impact of greater utilization.

• Cosmetic procedures and reconstructive surgery will remain safe havens. "They may try to pass a cosmetic procedure tax, but I think the fact that you have another source of income is very important," noted Dr. Coldiron, a dermatologist at the University of Cincinnati.

He recommended that dermatologists temper their income projections for the coming half-decade: "Don’t promise big salaries to new associates, only a percentage of income collected."

Also, read the fine print before jumping on board one of the accountable care organizations that are springing up. "This is government-driven managed care with capitation. What they’re going to do is extract from the specialists and give back to primary care. It’s kind of a loser’s game," he said.

Beyond the next 5 years, however, the outlook for dermatology is bright, Dr. Coldiron stressed.

"Be strong. We are not greedy specialists; we are a frontline specialty fighting an epidemic of skin cancer. We are needed by our patients and by the health care system. The pendulum will eventually swing back our way," he concluded.

Dr. Coldiron reported having no relevant financial conflicts. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Dr. Brett M. Coldiron is a sort of latter-day Paul Revere, travelling far and wide to spread the alarm to his fellow dermatologists – not of Redcoats a’coming, but of the need to prepare for looming economic hard times.

"I wasn’t invited to speak at your meeting, so I invited myself," he declared by way of introduction at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF), as he launched into an analysis of dermatology’s near-term financial future.

"I’m here to present your 5-year economic plan – what you can expect. I think you can plan your next 5 years based on these predictions. It’s not pretty; and it’s not kind," cautioned Dr. Coldiron, whose expertise regarding health care policy and reform has been forged through long-term involvement representing dermatology on the American Medical Association’s Relative Value Scale Update, Health Care Finance, and Government Health Care Policy committees.

His core message to his colleagues boiled down to this: "Don’t build palaces. It’s time to hunker down."

Dermatology is a heavily procedurally oriented, small specialty – less then 1% of all physicians – which has experienced dramatic growth in procedure volume over the past couple decades. As such, it is a high-priority target for congressional cost-cutting efforts. In the first 4 months of next year, Dr. Coldiron said he expects reimbursement for codes pertaining to actinic keratosis treatment to be cut by 25%-50%, along with a roughly 20% reduction in payment for Mohs surgery. And that’s just the beginning.

Dermatology and other small specialties will bear the brunt of any cost-savings attempts by Congress. Dermatology has powerful enemies in Congress, the Centers for Medicare and Medicaid Services, and the American Medical Association, who view dermatologists as overpaid, wasteful abusers of the system, explained Dr. Coldiron, who is president of the American College of Mohs Surgery and a 2013 member of the American Academy of Dermatology’s board of directors.

Among his predictions for the next 5 years:

• Hospitals and pharmacies, if squeezed too hard, will simply close. Insurers will move into other lines of business coverage. Pharmaceutical companies will reduce their research and development budgets. Thus, reducing physician income will be one of the few politically acceptable health care cost-cutting avenues available.

• There will be more bundling of minor procedures into evaluation and management fees.

• The government will attempt to force all physicians to accept Medicaid. "They’ll probably try to tie it to your acceptance of Medicare. Or maybe they’ll say, ‘We paid for 4 years of postgraduate education; now you owe us 4 years of taking Medicaid,’ " he said.

• The use of physician assistants and nurse practitioners will grow in dermatology. This will result in increased utilization and more intense billing audits along with reimbursement cuts aimed at cancelling out the economic impact of greater utilization.

• Cosmetic procedures and reconstructive surgery will remain safe havens. "They may try to pass a cosmetic procedure tax, but I think the fact that you have another source of income is very important," noted Dr. Coldiron, a dermatologist at the University of Cincinnati.

He recommended that dermatologists temper their income projections for the coming half-decade: "Don’t promise big salaries to new associates, only a percentage of income collected."

Also, read the fine print before jumping on board one of the accountable care organizations that are springing up. "This is government-driven managed care with capitation. What they’re going to do is extract from the specialists and give back to primary care. It’s kind of a loser’s game," he said.

Beyond the next 5 years, however, the outlook for dermatology is bright, Dr. Coldiron stressed.

"Be strong. We are not greedy specialists; we are a frontline specialty fighting an epidemic of skin cancer. We are needed by our patients and by the health care system. The pendulum will eventually swing back our way," he concluded.

Dr. Coldiron reported having no relevant financial conflicts. SDEF and this news organization are owned by Elsevier.

CHICAGO – Patients given a look at their coronary artery calcium CT scans are more likely to undertake cardiovascular risk reduction measures.

Further, the more abnormal the coronary artery calcium (CAC) score and its corresponding cardiac CT scan, the better the subsequent patient adherence with recommended risk reduction measures. So CAC scores are useful not only for risk stratification, but also for improving adherence to measures aimed at lowering risk, according to Dr. Nove Kalia of the University of Saskatchewan, Saskatoon.

He presented two related studies showing that patients who viewed their own CAC CT scan and had an elevated CAC score were more likely to lose weight and to adhere to prescribed statin therapy. He carried out both studies at Harbor-UCLA Medical Center in Torrance, Calif.

The weight loss study included 518 subjects followed for a mean of 3 years after their initial CAC CT scan. All participants were shown their scans and the significance of their CAC score was explained to them.

Any measurable weight loss at 3 years of follow up was present in 22% of subjects with a CAC score of 0, in 36% of those with a score of 1-99, in 32% of those with a score of 100-399, and in 38% of those with a score of 400 or above.

Compared to patients with a CAC score of 0, the likelihood of weight loss was 2.0-fold greater in patients with a CAC score of 1-99, 3.6-fold greater in those with a score of 100-399, and 3.3-fold greater in patients with a CAC score of 400 or above.

The higher the CAC score, the greater the average weight loss, ranging from 5 pounds in those with a score of 1-99 to 15 pounds with a score of 400 or greater.

"I think visualizing these coronary artery calcium images may be an important means of motivating patients even in an era of economic austerity," Dr. Kalia asserted. "The extra motivation you get from visualizing these images is helpful and probably translates into reduced long-term effects of coronary artery disease."

The statin adherence study involved 2,100 patients. At a mean follow up of 3 years, responses to a comprehensive patient questionnaire revealed that 36% of patients with a CAC score of 0 were compliant with their prescribed statin therapy, as compared to 52% of those with a CAC score of 1-99, 57% with a score of 100-399, and 59% with a CAC score of 400 or greater.

Compared to those with a CAC score of 0, adherence to statin therapy was 2.0-fold greater in patients with a score of 1-99, 2.4-fold greater with a score of 100-399, and 2.6-fold greater with a score of 400 or more.

Dr. Kalia reported having no financial conflicts.

CHICAGO – Patients given a look at their coronary artery calcium CT scans are more likely to undertake cardiovascular risk reduction measures.

Further, the more abnormal the coronary artery calcium (CAC) score and its corresponding cardiac CT scan, the better the subsequent patient adherence with recommended risk reduction measures. So CAC scores are useful not only for risk stratification, but also for improving adherence to measures aimed at lowering risk, according to Dr. Nove Kalia of the University of Saskatchewan, Saskatoon.

He presented two related studies showing that patients who viewed their own CAC CT scan and had an elevated CAC score were more likely to lose weight and to adhere to prescribed statin therapy. He carried out both studies at Harbor-UCLA Medical Center in Torrance, Calif.

The weight loss study included 518 subjects followed for a mean of 3 years after their initial CAC CT scan. All participants were shown their scans and the significance of their CAC score was explained to them.

Any measurable weight loss at 3 years of follow up was present in 22% of subjects with a CAC score of 0, in 36% of those with a score of 1-99, in 32% of those with a score of 100-399, and in 38% of those with a score of 400 or above.

Compared to patients with a CAC score of 0, the likelihood of weight loss was 2.0-fold greater in patients with a CAC score of 1-99, 3.6-fold greater in those with a score of 100-399, and 3.3-fold greater in patients with a CAC score of 400 or above.

The higher the CAC score, the greater the average weight loss, ranging from 5 pounds in those with a score of 1-99 to 15 pounds with a score of 400 or greater.

"I think visualizing these coronary artery calcium images may be an important means of motivating patients even in an era of economic austerity," Dr. Kalia asserted. "The extra motivation you get from visualizing these images is helpful and probably translates into reduced long-term effects of coronary artery disease."

The statin adherence study involved 2,100 patients. At a mean follow up of 3 years, responses to a comprehensive patient questionnaire revealed that 36% of patients with a CAC score of 0 were compliant with their prescribed statin therapy, as compared to 52% of those with a CAC score of 1-99, 57% with a score of 100-399, and 59% with a CAC score of 400 or greater.

Compared to those with a CAC score of 0, adherence to statin therapy was 2.0-fold greater in patients with a score of 1-99, 2.4-fold greater with a score of 100-399, and 2.6-fold greater with a score of 400 or more.

Dr. Kalia reported having no financial conflicts.

CHICAGO – Patients given a look at their coronary artery calcium CT scans are more likely to undertake cardiovascular risk reduction measures.

Further, the more abnormal the coronary artery calcium (CAC) score and its corresponding cardiac CT scan, the better the subsequent patient adherence with recommended risk reduction measures. So CAC scores are useful not only for risk stratification, but also for improving adherence to measures aimed at lowering risk, according to Dr. Nove Kalia of the University of Saskatchewan, Saskatoon.

He presented two related studies showing that patients who viewed their own CAC CT scan and had an elevated CAC score were more likely to lose weight and to adhere to prescribed statin therapy. He carried out both studies at Harbor-UCLA Medical Center in Torrance, Calif.

The weight loss study included 518 subjects followed for a mean of 3 years after their initial CAC CT scan. All participants were shown their scans and the significance of their CAC score was explained to them.

Any measurable weight loss at 3 years of follow up was present in 22% of subjects with a CAC score of 0, in 36% of those with a score of 1-99, in 32% of those with a score of 100-399, and in 38% of those with a score of 400 or above.

Compared to patients with a CAC score of 0, the likelihood of weight loss was 2.0-fold greater in patients with a CAC score of 1-99, 3.6-fold greater in those with a score of 100-399, and 3.3-fold greater in patients with a CAC score of 400 or above.

The higher the CAC score, the greater the average weight loss, ranging from 5 pounds in those with a score of 1-99 to 15 pounds with a score of 400 or greater.

"I think visualizing these coronary artery calcium images may be an important means of motivating patients even in an era of economic austerity," Dr. Kalia asserted. "The extra motivation you get from visualizing these images is helpful and probably translates into reduced long-term effects of coronary artery disease."

The statin adherence study involved 2,100 patients. At a mean follow up of 3 years, responses to a comprehensive patient questionnaire revealed that 36% of patients with a CAC score of 0 were compliant with their prescribed statin therapy, as compared to 52% of those with a CAC score of 1-99, 57% with a score of 100-399, and 59% with a CAC score of 400 or greater.

Compared to those with a CAC score of 0, adherence to statin therapy was 2.0-fold greater in patients with a score of 1-99, 2.4-fold greater with a score of 100-399, and 2.6-fold greater with a score of 400 or more.

Dr. Kalia reported having no financial conflicts.