CHICAGO – Access to equal care decreases but does not eliminate the survival disparities between black and white patients with rectal cancer, according to investigators from the University of Cincinnati, Ohio.

After rigorous propensity score matching of thousands of black and white patients for patient, disease, and treatment characteristics, median survival was 109.6 months among white patients and 85.8 months among black patients (J Am Coll Surg. 2015 Nov [doi: 10.1016/j.jamcollsurg.2015.07.056]).

“Blacks have worse outcomes, but we don’t have a clear explanation,” explained investigator and surgery resident Dr. Meghan Nolan. For now, the findings suggest that it might be a good idea to start screening black patients before age 50 years, perhaps even as early as age 40 years.

“We are urging people to screen at a lower age in black patients,” Dr. Nolan said at the annual clinical congress of the American College of Surgeons.

Racial disparities in rectal cancer are well known. The investigators wanted to see if they simply are because of unequal access to care, so they analyzed 178,414 white and 18,385 black patients in the National Cancer Data Base from 1998 to 2006.

Mean 5-year survival for blacks was 50.7%, compared with 56.2% for whites, and black patients were more likely to present with stage IV disease. Such findings aren’t new, the investigators noted.

To account for the difference in late-stage presentation, the investigators limited their analysis to patients with stage I-III rectal cancer. But even then, 5-year survival was 66.7% among whites and 58.7% among blacks.

That might have had something to do with the fact 85% of white patients, but only 78% of black patients, had surgery for those potentially curable lower-stage tumors. Among those who didn’t undergo surgery, patient refusal was slightly more common among black patients than white patients, which suggests that “cultural factors may be playing a role” in the surgery disparity, Dr. Nolan said.

The investigators controlled for the different surgery rates by limiting their analysis to stage I-III patients who had appropriate operations. The survival gap narrowed but did not disappear: 65.8% of white patients were alive at 5 years, compared with 61% of black patients. Blacks were also more likely to have positive margins on pathology. “I’m not sure why. That was a surprise,” Dr. Nolan said.

The propensity score matching led the team to conclude that there’s more at work than differences in access to care. A total of 7,569 pairs of black and white patients were matched for age at diagnosis, gender, insurance coverage, income, education, facility type, tumor stage, Charlson-Deyo score, surgical management, margin status, and other potential confounders.

Every matched patient completed their recommended therapy, and there was no statistical difference between matched black and white patients who received appropriate, stage-specific chemoradiation. Still, the survival differences persisted.

Dr. Nolan had no relevant disclosures.

[email protected]

CHICAGO – Access to equal care decreases but does not eliminate the survival disparities between black and white patients with rectal cancer, according to investigators from the University of Cincinnati, Ohio.

After rigorous propensity score matching of thousands of black and white patients for patient, disease, and treatment characteristics, median survival was 109.6 months among white patients and 85.8 months among black patients (J Am Coll Surg. 2015 Nov [doi: 10.1016/j.jamcollsurg.2015.07.056]).

“Blacks have worse outcomes, but we don’t have a clear explanation,” explained investigator and surgery resident Dr. Meghan Nolan. For now, the findings suggest that it might be a good idea to start screening black patients before age 50 years, perhaps even as early as age 40 years.

“We are urging people to screen at a lower age in black patients,” Dr. Nolan said at the annual clinical congress of the American College of Surgeons.

Racial disparities in rectal cancer are well known. The investigators wanted to see if they simply are because of unequal access to care, so they analyzed 178,414 white and 18,385 black patients in the National Cancer Data Base from 1998 to 2006.

Mean 5-year survival for blacks was 50.7%, compared with 56.2% for whites, and black patients were more likely to present with stage IV disease. Such findings aren’t new, the investigators noted.

To account for the difference in late-stage presentation, the investigators limited their analysis to patients with stage I-III rectal cancer. But even then, 5-year survival was 66.7% among whites and 58.7% among blacks.

That might have had something to do with the fact 85% of white patients, but only 78% of black patients, had surgery for those potentially curable lower-stage tumors. Among those who didn’t undergo surgery, patient refusal was slightly more common among black patients than white patients, which suggests that “cultural factors may be playing a role” in the surgery disparity, Dr. Nolan said.

The investigators controlled for the different surgery rates by limiting their analysis to stage I-III patients who had appropriate operations. The survival gap narrowed but did not disappear: 65.8% of white patients were alive at 5 years, compared with 61% of black patients. Blacks were also more likely to have positive margins on pathology. “I’m not sure why. That was a surprise,” Dr. Nolan said.

The propensity score matching led the team to conclude that there’s more at work than differences in access to care. A total of 7,569 pairs of black and white patients were matched for age at diagnosis, gender, insurance coverage, income, education, facility type, tumor stage, Charlson-Deyo score, surgical management, margin status, and other potential confounders.

Every matched patient completed their recommended therapy, and there was no statistical difference between matched black and white patients who received appropriate, stage-specific chemoradiation. Still, the survival differences persisted.

Dr. Nolan had no relevant disclosures.

[email protected]

CHICAGO – Access to equal care decreases but does not eliminate the survival disparities between black and white patients with rectal cancer, according to investigators from the University of Cincinnati, Ohio.

After rigorous propensity score matching of thousands of black and white patients for patient, disease, and treatment characteristics, median survival was 109.6 months among white patients and 85.8 months among black patients (J Am Coll Surg. 2015 Nov [doi: 10.1016/j.jamcollsurg.2015.07.056]).

“Blacks have worse outcomes, but we don’t have a clear explanation,” explained investigator and surgery resident Dr. Meghan Nolan. For now, the findings suggest that it might be a good idea to start screening black patients before age 50 years, perhaps even as early as age 40 years.

“We are urging people to screen at a lower age in black patients,” Dr. Nolan said at the annual clinical congress of the American College of Surgeons.

Racial disparities in rectal cancer are well known. The investigators wanted to see if they simply are because of unequal access to care, so they analyzed 178,414 white and 18,385 black patients in the National Cancer Data Base from 1998 to 2006.

Mean 5-year survival for blacks was 50.7%, compared with 56.2% for whites, and black patients were more likely to present with stage IV disease. Such findings aren’t new, the investigators noted.

To account for the difference in late-stage presentation, the investigators limited their analysis to patients with stage I-III rectal cancer. But even then, 5-year survival was 66.7% among whites and 58.7% among blacks.

That might have had something to do with the fact 85% of white patients, but only 78% of black patients, had surgery for those potentially curable lower-stage tumors. Among those who didn’t undergo surgery, patient refusal was slightly more common among black patients than white patients, which suggests that “cultural factors may be playing a role” in the surgery disparity, Dr. Nolan said.

The investigators controlled for the different surgery rates by limiting their analysis to stage I-III patients who had appropriate operations. The survival gap narrowed but did not disappear: 65.8% of white patients were alive at 5 years, compared with 61% of black patients. Blacks were also more likely to have positive margins on pathology. “I’m not sure why. That was a surprise,” Dr. Nolan said.

The propensity score matching led the team to conclude that there’s more at work than differences in access to care. A total of 7,569 pairs of black and white patients were matched for age at diagnosis, gender, insurance coverage, income, education, facility type, tumor stage, Charlson-Deyo score, surgical management, margin status, and other potential confounders.

Every matched patient completed their recommended therapy, and there was no statistical difference between matched black and white patients who received appropriate, stage-specific chemoradiation. Still, the survival differences persisted.

Dr. Nolan had no relevant disclosures.

[email protected]

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr. Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, N.C., and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Dr. Williams had no disclosures. The senior author disclosed research funding from the Medtronic Foundation.

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr. Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, N.C., and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Dr. Williams had no disclosures. The senior author disclosed research funding from the Medtronic Foundation.

Most adults who survived out-of-hospital cardiac arrests remained neurologically intact, even if cardiopulmonary resuscitation lasted longer than has been recommended, authors of a retrospective observational study reported at the American Heart Association scientific sessions.

Dr. Jefferson Williams of the Wake County Department of Emergency Medical Services in Raleigh, N.C., and his associates studied 3,814 adults who had a cardiac arrest outside the hospital between 2005 and 2014. Only 12% of patients survived, but 84% of survivors had a cerebral performance category of 1 or 2, including 10% who underwent more than 35 minutes of CPR before reaching the hospital.

Neurologically intact survival was associated with having an initial shockable rhythm, a bystander-witnessed arrest, and return of spontaneous circulation in the field rather than in the hospital. Age, basic airway management, and therapeutic hypothermia phase also predicted survival with intact brain function, but duration of CPR did not.

Dr. Williams had no disclosures. The senior author disclosed research funding from the Medtronic Foundation.

Box of clopidogrel (Plavix)

A review conducted by the US Food and Drug Administration (FDA) indicates that long-term use of the antiplatelet drug clopidogrel (Plavix) does not increase or decrease the overall risk of death in patients with, or at risk for, heart disease.

In addition, the FDA said there is no evidence to suggest that clopidogrel increases the risk of cancer or death from cancer.

These findings contradict those of the Dual Antiplatelet Therapy (DAPT) trial, the study that prompted the FDA’s review.

In this trial, researchers compared 12 months of DAPT (either clopidogrel or prasugrel plus aspirin) to 30 months of DAPT in patients who had a drug-eluting coronary stent.

Compared to patients taking clopidogrel for 12 months, patients who received clopidogrel for 30 months had lower rates of heart attacks and stent thrombosis but higher rates of death, primarily from cancer or trauma.

To investigate these findings, the FDA examined data from the DAPT trial and performed trial-level meta-analyses of other large, long-term trials.

The trials had a clopidogrel-plus-aspirin arm (long-term treatment was 12 months or longer) and a comparator arm of either aspirin alone or short-term clopidogrel plus aspirin (6 months or less). They also had a planned follow-up of at least 1 year.

All-cause death

In the DAPT trial, extended use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs 1.5% for 12 months). But there was no increased risk for prasugrel plus aspirin (1.6% for 30 months vs 1.6% for 12 months).

The FDA’s initial meta-analysis on mortality included 12 trials (56,799 patients). The incidence of all-cause mortality was 6.7% for the long-term clopidogrel-plus-aspirin arm and 6.6% for the comparator arm, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% CI, -0.35%-0.44%).

The FDA also conducted a meta-analysis of 9 of the 12 trials (45,374 patients), which enrolled patients with coronary artery disease or patients at risk of coronary artery disease. This analysis showed no difference in the risk of all-cause mortality—MH RD of -0.07% (95% CI, -0.43%-0.29%).

Cancer and death in DAPT

In the DAPT trial, the risk of cancer reported as an adverse event was not different between the 30-month (2.4% ) and 12-month (2.3%) groups receiving clopidogrel, when considering cancers reported after enrollment (from month 0 to 33 of the study).

The FDA performed several analyses of the cancer adverse event data, and the relative risk of cancer for the 30-month vs 12-month arm in the clopidogrel group ranged from 0.95 to 1.2, depending on the analysis.

Similar analyses for the prasugrel group revealed relative risks of cancer-related adverse events ranging from 1.4 to 1.6.

The FDA noted that, although there was no increase in the risk of cancer-related adverse events for clopidogrel in the 30-month arm, the risk of cancer-related death was higher than in the 12-month arm—0.7% and 0.2%, respectively.

For prasugrel, there was a trend toward a higher risk of cancer adverse events in the 30-month arm than in the 12-month arm, but the risk of cancer death was identical in both arms—0.4% vs 0.4%.

The FDA said these findings are difficult to reconcile.

Meta-analyses of cancer and death

The FDA performed 2 trial-level meta-analyses to investigate the role of clopidogrel in cancer and cancer death.

The first was an analysis of cancer-related adverse events from 4 trials (37,835 patients) that compared long-term clopidogrel and aspirin to either aspirin alone or short-term clopidogrel plus aspirin.

The incidence of cancer adverse events was 4.2% for the long-term clopidogrel-plus-aspirin arm and 4.0% for the comparator arm (MH RD of 0.19%; 95% CI, -0.2%-0.59%).

The FDA conducted the second meta-analysis to assess cancer-related death. The analysis included 5 trials (40,855 patients).

The incidence of cancer death was 0.9% for the long-term clopidogrel-plus-aspirin arm and 1.1% for the comparator arm (MH RD of -0.14%; 95% CI, -0.33%-0.06%).

The FDA said that, taken together, the results of this review do not suggest an increased risk of cancer adverse events, cancer-related death, or all-cause mortality with long-term clopidogrel therapy.

More details can be found in the FDA’s Drug Safety Communication on this topic.

Box of clopidogrel (Plavix)

A review conducted by the US Food and Drug Administration (FDA) indicates that long-term use of the antiplatelet drug clopidogrel (Plavix) does not increase or decrease the overall risk of death in patients with, or at risk for, heart disease.

In addition, the FDA said there is no evidence to suggest that clopidogrel increases the risk of cancer or death from cancer.

These findings contradict those of the Dual Antiplatelet Therapy (DAPT) trial, the study that prompted the FDA’s review.

In this trial, researchers compared 12 months of DAPT (either clopidogrel or prasugrel plus aspirin) to 30 months of DAPT in patients who had a drug-eluting coronary stent.

Compared to patients taking clopidogrel for 12 months, patients who received clopidogrel for 30 months had lower rates of heart attacks and stent thrombosis but higher rates of death, primarily from cancer or trauma.

To investigate these findings, the FDA examined data from the DAPT trial and performed trial-level meta-analyses of other large, long-term trials.

The trials had a clopidogrel-plus-aspirin arm (long-term treatment was 12 months or longer) and a comparator arm of either aspirin alone or short-term clopidogrel plus aspirin (6 months or less). They also had a planned follow-up of at least 1 year.

All-cause death

In the DAPT trial, extended use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs 1.5% for 12 months). But there was no increased risk for prasugrel plus aspirin (1.6% for 30 months vs 1.6% for 12 months).

The FDA’s initial meta-analysis on mortality included 12 trials (56,799 patients). The incidence of all-cause mortality was 6.7% for the long-term clopidogrel-plus-aspirin arm and 6.6% for the comparator arm, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% CI, -0.35%-0.44%).

The FDA also conducted a meta-analysis of 9 of the 12 trials (45,374 patients), which enrolled patients with coronary artery disease or patients at risk of coronary artery disease. This analysis showed no difference in the risk of all-cause mortality—MH RD of -0.07% (95% CI, -0.43%-0.29%).

Cancer and death in DAPT

In the DAPT trial, the risk of cancer reported as an adverse event was not different between the 30-month (2.4% ) and 12-month (2.3%) groups receiving clopidogrel, when considering cancers reported after enrollment (from month 0 to 33 of the study).

The FDA performed several analyses of the cancer adverse event data, and the relative risk of cancer for the 30-month vs 12-month arm in the clopidogrel group ranged from 0.95 to 1.2, depending on the analysis.

Similar analyses for the prasugrel group revealed relative risks of cancer-related adverse events ranging from 1.4 to 1.6.

The FDA noted that, although there was no increase in the risk of cancer-related adverse events for clopidogrel in the 30-month arm, the risk of cancer-related death was higher than in the 12-month arm—0.7% and 0.2%, respectively.

For prasugrel, there was a trend toward a higher risk of cancer adverse events in the 30-month arm than in the 12-month arm, but the risk of cancer death was identical in both arms—0.4% vs 0.4%.

The FDA said these findings are difficult to reconcile.

Meta-analyses of cancer and death

The FDA performed 2 trial-level meta-analyses to investigate the role of clopidogrel in cancer and cancer death.

The first was an analysis of cancer-related adverse events from 4 trials (37,835 patients) that compared long-term clopidogrel and aspirin to either aspirin alone or short-term clopidogrel plus aspirin.

The incidence of cancer adverse events was 4.2% for the long-term clopidogrel-plus-aspirin arm and 4.0% for the comparator arm (MH RD of 0.19%; 95% CI, -0.2%-0.59%).

The FDA conducted the second meta-analysis to assess cancer-related death. The analysis included 5 trials (40,855 patients).

The incidence of cancer death was 0.9% for the long-term clopidogrel-plus-aspirin arm and 1.1% for the comparator arm (MH RD of -0.14%; 95% CI, -0.33%-0.06%).

The FDA said that, taken together, the results of this review do not suggest an increased risk of cancer adverse events, cancer-related death, or all-cause mortality with long-term clopidogrel therapy.

More details can be found in the FDA’s Drug Safety Communication on this topic.

Box of clopidogrel (Plavix)

A review conducted by the US Food and Drug Administration (FDA) indicates that long-term use of the antiplatelet drug clopidogrel (Plavix) does not increase or decrease the overall risk of death in patients with, or at risk for, heart disease.

In addition, the FDA said there is no evidence to suggest that clopidogrel increases the risk of cancer or death from cancer.

These findings contradict those of the Dual Antiplatelet Therapy (DAPT) trial, the study that prompted the FDA’s review.

In this trial, researchers compared 12 months of DAPT (either clopidogrel or prasugrel plus aspirin) to 30 months of DAPT in patients who had a drug-eluting coronary stent.

Compared to patients taking clopidogrel for 12 months, patients who received clopidogrel for 30 months had lower rates of heart attacks and stent thrombosis but higher rates of death, primarily from cancer or trauma.

To investigate these findings, the FDA examined data from the DAPT trial and performed trial-level meta-analyses of other large, long-term trials.

The trials had a clopidogrel-plus-aspirin arm (long-term treatment was 12 months or longer) and a comparator arm of either aspirin alone or short-term clopidogrel plus aspirin (6 months or less). They also had a planned follow-up of at least 1 year.

All-cause death

In the DAPT trial, extended use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs 1.5% for 12 months). But there was no increased risk for prasugrel plus aspirin (1.6% for 30 months vs 1.6% for 12 months).

The FDA’s initial meta-analysis on mortality included 12 trials (56,799 patients). The incidence of all-cause mortality was 6.7% for the long-term clopidogrel-plus-aspirin arm and 6.6% for the comparator arm, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% CI, -0.35%-0.44%).

The FDA also conducted a meta-analysis of 9 of the 12 trials (45,374 patients), which enrolled patients with coronary artery disease or patients at risk of coronary artery disease. This analysis showed no difference in the risk of all-cause mortality—MH RD of -0.07% (95% CI, -0.43%-0.29%).

Cancer and death in DAPT

In the DAPT trial, the risk of cancer reported as an adverse event was not different between the 30-month (2.4% ) and 12-month (2.3%) groups receiving clopidogrel, when considering cancers reported after enrollment (from month 0 to 33 of the study).

The FDA performed several analyses of the cancer adverse event data, and the relative risk of cancer for the 30-month vs 12-month arm in the clopidogrel group ranged from 0.95 to 1.2, depending on the analysis.

Similar analyses for the prasugrel group revealed relative risks of cancer-related adverse events ranging from 1.4 to 1.6.

The FDA noted that, although there was no increase in the risk of cancer-related adverse events for clopidogrel in the 30-month arm, the risk of cancer-related death was higher than in the 12-month arm—0.7% and 0.2%, respectively.

For prasugrel, there was a trend toward a higher risk of cancer adverse events in the 30-month arm than in the 12-month arm, but the risk of cancer death was identical in both arms—0.4% vs 0.4%.

The FDA said these findings are difficult to reconcile.

Meta-analyses of cancer and death

The FDA performed 2 trial-level meta-analyses to investigate the role of clopidogrel in cancer and cancer death.

The first was an analysis of cancer-related adverse events from 4 trials (37,835 patients) that compared long-term clopidogrel and aspirin to either aspirin alone or short-term clopidogrel plus aspirin.

The incidence of cancer adverse events was 4.2% for the long-term clopidogrel-plus-aspirin arm and 4.0% for the comparator arm (MH RD of 0.19%; 95% CI, -0.2%-0.59%).

The FDA conducted the second meta-analysis to assess cancer-related death. The analysis included 5 trials (40,855 patients).

The incidence of cancer death was 0.9% for the long-term clopidogrel-plus-aspirin arm and 1.1% for the comparator arm (MH RD of -0.14%; 95% CI, -0.33%-0.06%).

The FDA said that, taken together, the results of this review do not suggest an increased risk of cancer adverse events, cancer-related death, or all-cause mortality with long-term clopidogrel therapy.

More details can be found in the FDA’s Drug Safety Communication on this topic.

LAS VEGAS – The addition of field treatment to targeted lesion treatment may offer patients the best outcomes when addressing actinic keratoses (AKs), said Dr. David M. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk, Virginia.

Speaking at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Dr. Pariser said that the rationale for treating AKs stems from the fact that not all AKs will transform to squamous cell carcinoma (SCC). “We don’t know which ones will and which ones won’t.” Though treatment can be guided by a shared decision-making approach, a personal history of multiple skin cancers is an obvious reason for concern, as is any drug-related or disease-related immunosuppression, he added.

Available treatments for AKs include cryosurgery, curettage, and electrodessication; photodynamic therapy (PDT); and topical agents, including 5-fluorouracil (5-FU), diclofenac, imiquimod, and ingenol mebutate.

“Cryosurgery is what most of us do for most AKs,” said Dr. Pariser, observing that this is a bread-and-butter procedure that is part of the backbone of most dermatology practices. Cryosurgery, curettage, and electrodessication are all used to treat discrete lesions, especially for higher-grade AKs.

However, Dr. Pariser noted that many AKs occur in a “field of cancerization.” This is a larger area of photodamaged skin; the skin may not appear grossly abnormal, but deranged areas will be diffusely evident with fluorescence detection, “indicating that all of this area was damaged,” he said.

PDT and topical agents effectively provide field treatment, and do not just address discrete lesions, although field treatment is technically an off-label use for these modalities, he added.

Lower concentrations and shorter courses of topical agents may be effective and better tolerated by patients, Dr. Pariser said. In clinical trials, for example, the efficacy of imiquimod 2.5% and 3.75% has been comparable to the stronger 5% formulation. Treatment cycles lasting 2 rather than 3 weeks have also shown similar efficacy. The greater palatability of these regimens to patients may increase real-world adherence as well.

Cure rates for PDT range from 67% to 92% for both the blue light–aminolevulinic acid modality and the red light–methyl aminolevulinate more commonly used in Europe. These modalities also treat a broad field, offer cure rates comparable to other topical modalities, and result in less scarring than destructive modalities, Dr. Pariser said.

The pain of PDT may be understandably off-putting for some patients, he commented. In the United States, investigators are experimenting with shorter incubation times for the ALA topical solutions. One study found comparable reductions in the number of AKs by the end of the study period for 1 versus 2 or 3 hours of incubation, and a 2-hour incubation period with spot treatment only was also similarly effective. Clearance rates ranged from about 70%-80%, and all were highly statistically significant, compared with the vehicle-only arm. However, “a second treatment at week 8 seems to be necessary for improved efficacy,” Dr. Pariser said.

Another treatment strategy currently being investigated is “painless PDT,” where the agent is applied and the field is illuminated immediately. Photo-bleaching degrades the protoporphyrins as they are produced, dramatically reducing patient discomfort. Efficacy is promising, he added.

In Europe, “daylight PDT” is being explored – the photosensitizing agent is applied, and the patient simply goes about his or her daily business in normal daylight. This is a nearly painless therapy and shows promise for efficacy. However, said Dr. Pariser, the realities of practice economics make it very unlikely that daylight PDT will catch on in the United States, since the daylight exposure does not represent a billable procedure.

Dr. Pariser reiterated that regardless of the modality, “field therapy has better long-term efficacy rates and better sustained clearance no matter which one of the agents we use, and combination therapy [of lesional and field treatment] seems to be the most effective.”

Dr. Pariser disclosed that he is an investigator and consultant for DUSA Pharmaceuticals, Photocure, and LEO Pharma, and that he discussed off-label uses of drugs and devices.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – The addition of field treatment to targeted lesion treatment may offer patients the best outcomes when addressing actinic keratoses (AKs), said Dr. David M. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk, Virginia.

Speaking at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Dr. Pariser said that the rationale for treating AKs stems from the fact that not all AKs will transform to squamous cell carcinoma (SCC). “We don’t know which ones will and which ones won’t.” Though treatment can be guided by a shared decision-making approach, a personal history of multiple skin cancers is an obvious reason for concern, as is any drug-related or disease-related immunosuppression, he added.

Available treatments for AKs include cryosurgery, curettage, and electrodessication; photodynamic therapy (PDT); and topical agents, including 5-fluorouracil (5-FU), diclofenac, imiquimod, and ingenol mebutate.

“Cryosurgery is what most of us do for most AKs,” said Dr. Pariser, observing that this is a bread-and-butter procedure that is part of the backbone of most dermatology practices. Cryosurgery, curettage, and electrodessication are all used to treat discrete lesions, especially for higher-grade AKs.

However, Dr. Pariser noted that many AKs occur in a “field of cancerization.” This is a larger area of photodamaged skin; the skin may not appear grossly abnormal, but deranged areas will be diffusely evident with fluorescence detection, “indicating that all of this area was damaged,” he said.

PDT and topical agents effectively provide field treatment, and do not just address discrete lesions, although field treatment is technically an off-label use for these modalities, he added.

Lower concentrations and shorter courses of topical agents may be effective and better tolerated by patients, Dr. Pariser said. In clinical trials, for example, the efficacy of imiquimod 2.5% and 3.75% has been comparable to the stronger 5% formulation. Treatment cycles lasting 2 rather than 3 weeks have also shown similar efficacy. The greater palatability of these regimens to patients may increase real-world adherence as well.

Cure rates for PDT range from 67% to 92% for both the blue light–aminolevulinic acid modality and the red light–methyl aminolevulinate more commonly used in Europe. These modalities also treat a broad field, offer cure rates comparable to other topical modalities, and result in less scarring than destructive modalities, Dr. Pariser said.

The pain of PDT may be understandably off-putting for some patients, he commented. In the United States, investigators are experimenting with shorter incubation times for the ALA topical solutions. One study found comparable reductions in the number of AKs by the end of the study period for 1 versus 2 or 3 hours of incubation, and a 2-hour incubation period with spot treatment only was also similarly effective. Clearance rates ranged from about 70%-80%, and all were highly statistically significant, compared with the vehicle-only arm. However, “a second treatment at week 8 seems to be necessary for improved efficacy,” Dr. Pariser said.

Another treatment strategy currently being investigated is “painless PDT,” where the agent is applied and the field is illuminated immediately. Photo-bleaching degrades the protoporphyrins as they are produced, dramatically reducing patient discomfort. Efficacy is promising, he added.

In Europe, “daylight PDT” is being explored – the photosensitizing agent is applied, and the patient simply goes about his or her daily business in normal daylight. This is a nearly painless therapy and shows promise for efficacy. However, said Dr. Pariser, the realities of practice economics make it very unlikely that daylight PDT will catch on in the United States, since the daylight exposure does not represent a billable procedure.

Dr. Pariser reiterated that regardless of the modality, “field therapy has better long-term efficacy rates and better sustained clearance no matter which one of the agents we use, and combination therapy [of lesional and field treatment] seems to be the most effective.”

Dr. Pariser disclosed that he is an investigator and consultant for DUSA Pharmaceuticals, Photocure, and LEO Pharma, and that he discussed off-label uses of drugs and devices.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – The addition of field treatment to targeted lesion treatment may offer patients the best outcomes when addressing actinic keratoses (AKs), said Dr. David M. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk, Virginia.

Speaking at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Dr. Pariser said that the rationale for treating AKs stems from the fact that not all AKs will transform to squamous cell carcinoma (SCC). “We don’t know which ones will and which ones won’t.” Though treatment can be guided by a shared decision-making approach, a personal history of multiple skin cancers is an obvious reason for concern, as is any drug-related or disease-related immunosuppression, he added.

Available treatments for AKs include cryosurgery, curettage, and electrodessication; photodynamic therapy (PDT); and topical agents, including 5-fluorouracil (5-FU), diclofenac, imiquimod, and ingenol mebutate.

“Cryosurgery is what most of us do for most AKs,” said Dr. Pariser, observing that this is a bread-and-butter procedure that is part of the backbone of most dermatology practices. Cryosurgery, curettage, and electrodessication are all used to treat discrete lesions, especially for higher-grade AKs.

However, Dr. Pariser noted that many AKs occur in a “field of cancerization.” This is a larger area of photodamaged skin; the skin may not appear grossly abnormal, but deranged areas will be diffusely evident with fluorescence detection, “indicating that all of this area was damaged,” he said.

PDT and topical agents effectively provide field treatment, and do not just address discrete lesions, although field treatment is technically an off-label use for these modalities, he added.

Lower concentrations and shorter courses of topical agents may be effective and better tolerated by patients, Dr. Pariser said. In clinical trials, for example, the efficacy of imiquimod 2.5% and 3.75% has been comparable to the stronger 5% formulation. Treatment cycles lasting 2 rather than 3 weeks have also shown similar efficacy. The greater palatability of these regimens to patients may increase real-world adherence as well.

Cure rates for PDT range from 67% to 92% for both the blue light–aminolevulinic acid modality and the red light–methyl aminolevulinate more commonly used in Europe. These modalities also treat a broad field, offer cure rates comparable to other topical modalities, and result in less scarring than destructive modalities, Dr. Pariser said.

The pain of PDT may be understandably off-putting for some patients, he commented. In the United States, investigators are experimenting with shorter incubation times for the ALA topical solutions. One study found comparable reductions in the number of AKs by the end of the study period for 1 versus 2 or 3 hours of incubation, and a 2-hour incubation period with spot treatment only was also similarly effective. Clearance rates ranged from about 70%-80%, and all were highly statistically significant, compared with the vehicle-only arm. However, “a second treatment at week 8 seems to be necessary for improved efficacy,” Dr. Pariser said.

Another treatment strategy currently being investigated is “painless PDT,” where the agent is applied and the field is illuminated immediately. Photo-bleaching degrades the protoporphyrins as they are produced, dramatically reducing patient discomfort. Efficacy is promising, he added.

In Europe, “daylight PDT” is being explored – the photosensitizing agent is applied, and the patient simply goes about his or her daily business in normal daylight. This is a nearly painless therapy and shows promise for efficacy. However, said Dr. Pariser, the realities of practice economics make it very unlikely that daylight PDT will catch on in the United States, since the daylight exposure does not represent a billable procedure.

Dr. Pariser reiterated that regardless of the modality, “field therapy has better long-term efficacy rates and better sustained clearance no matter which one of the agents we use, and combination therapy [of lesional and field treatment] seems to be the most effective.”

Dr. Pariser disclosed that he is an investigator and consultant for DUSA Pharmaceuticals, Photocure, and LEO Pharma, and that he discussed off-label uses of drugs and devices.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – New acne treatment strategies that address the issue of antibiotic resistance include subantimicrobial dosing; new, narrower-spectrum antibiotics; and topical use of tetracycline-family antibiotics, according to Dr. Linda Stein Gold, a dermatologist at Henry Ford Hospital, Detroit.

Oral antibiotics have long been a mainstay of acne treatment, but long-term use of low-dose antibiotics may be contributing to the global crisis of antibiotic resistance. At least 2 million people become infected with resistant bacteria yearly in the United States alone, and at least 23,000 people die yearly from these infections, she noted.

“In dermatology we use antibiotics quite a bit, and we want to make sure when we’re utilizing drugs, we’re utilizing them in the best possible way,” Dr. Stein Gold said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. Finding the right antibiotic dose for effective treatment of acne can be a challenge, she noted. “Is more better? Is too little bad?”

In a review of new treatment strategies that address these concerns without compromising efficacy, Dr. Stein Gold said that the rationale for using subantimicrobial antibiotic dosing comes from the anti-inflammatory effect seen with many antibiotics, even with doses lower than needed for antimicrobial action.

For example, a study of a subantimicrobial-dose of doxycycline found that when adults with moderate acne were treated with the antibiotic (20 mg, twice daily) for 6 months, their acne significantly improved. The number of comedones, inflammatory lesions, and noninflammatory lesions improved significantly compared with those on placebo (Arch Dermatol. 2003 Apr; 139:459-64).

In another head-to-head trial that compared low-dose modified-release doxycycline with placebo or 100 mg of doxycycline, the lower dose outperformed both placebo and full-strength antibiotics. No resistant organisms were found among skin flora in the subjects, and the microbiota of the patients’ skin did not change significantly during the study period, she said.

Dr. Stein Gold’s work also suggests that systemic antibiotics may not be necessary for all patients with acne: In a study, after 12 weeks of treatment, adapalene plus benzoyl peroxide, in combination with doxycycline, resulted in significantly more patients with clear or almost-clear skin than with vehicle alone plus doxycycline. “Antibiotics are not always the golden nugget in the treatment of acne,” she commented.

Another tactic is to treat with antibiotics for a period of 3-6 months along with potent topicals, to get skin clear or almost clear, then discontinue the antibiotic and continue topical treatment. Many patients will be able to maintain clear skin on this regime, she noted.

A new tetracycline-family antibiotic, sarecycline, is in phase III trials for acne vulgaris and in phase II trials for acne rosacea. Sarecycline, “compared with existing tetracycline antibiotics, showed improved anti-inflammatory properties and a narrower spectrum of activity,” Dr. Stein Gold said.

A topical minocycline in a foam formulation shows promising results for tolerability and efficacy in phase II trials for moderate and severe acne, she added. Dapsone as a 7.5% topical gel formulation is in phase III clinical trials as well.

Another antibiotic with a long history of systemic use for acne, clindamycin, is also showing promising results in combination with benzoyl peroxide (1.2%/3.75% gel). A 12-week double-blind study of the combination, compared with vehicle alone for individuals with moderate or severe acne, showed significant improvement in comedonal and inflammatory lesions, as well as overall global improvement in severity, for the treatment arm, she said (J Drugs Dermatol. 2014 Sep;13[9]:1083-9).

Dr. Stein Gold reports being a consultant and investigator for Galderma, Stiefel Laboratories, and Allergan; a consultant and speaker for Valeant; a speaker for Ranbaxy Laboratories, Promius Pharma, and Actavis; and a medical/legal consultant for Roche.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – New acne treatment strategies that address the issue of antibiotic resistance include subantimicrobial dosing; new, narrower-spectrum antibiotics; and topical use of tetracycline-family antibiotics, according to Dr. Linda Stein Gold, a dermatologist at Henry Ford Hospital, Detroit.

Oral antibiotics have long been a mainstay of acne treatment, but long-term use of low-dose antibiotics may be contributing to the global crisis of antibiotic resistance. At least 2 million people become infected with resistant bacteria yearly in the United States alone, and at least 23,000 people die yearly from these infections, she noted.

“In dermatology we use antibiotics quite a bit, and we want to make sure when we’re utilizing drugs, we’re utilizing them in the best possible way,” Dr. Stein Gold said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. Finding the right antibiotic dose for effective treatment of acne can be a challenge, she noted. “Is more better? Is too little bad?”

In a review of new treatment strategies that address these concerns without compromising efficacy, Dr. Stein Gold said that the rationale for using subantimicrobial antibiotic dosing comes from the anti-inflammatory effect seen with many antibiotics, even with doses lower than needed for antimicrobial action.

For example, a study of a subantimicrobial-dose of doxycycline found that when adults with moderate acne were treated with the antibiotic (20 mg, twice daily) for 6 months, their acne significantly improved. The number of comedones, inflammatory lesions, and noninflammatory lesions improved significantly compared with those on placebo (Arch Dermatol. 2003 Apr; 139:459-64).

In another head-to-head trial that compared low-dose modified-release doxycycline with placebo or 100 mg of doxycycline, the lower dose outperformed both placebo and full-strength antibiotics. No resistant organisms were found among skin flora in the subjects, and the microbiota of the patients’ skin did not change significantly during the study period, she said.

Dr. Stein Gold’s work also suggests that systemic antibiotics may not be necessary for all patients with acne: In a study, after 12 weeks of treatment, adapalene plus benzoyl peroxide, in combination with doxycycline, resulted in significantly more patients with clear or almost-clear skin than with vehicle alone plus doxycycline. “Antibiotics are not always the golden nugget in the treatment of acne,” she commented.

Another tactic is to treat with antibiotics for a period of 3-6 months along with potent topicals, to get skin clear or almost clear, then discontinue the antibiotic and continue topical treatment. Many patients will be able to maintain clear skin on this regime, she noted.

A new tetracycline-family antibiotic, sarecycline, is in phase III trials for acne vulgaris and in phase II trials for acne rosacea. Sarecycline, “compared with existing tetracycline antibiotics, showed improved anti-inflammatory properties and a narrower spectrum of activity,” Dr. Stein Gold said.

A topical minocycline in a foam formulation shows promising results for tolerability and efficacy in phase II trials for moderate and severe acne, she added. Dapsone as a 7.5% topical gel formulation is in phase III clinical trials as well.

Another antibiotic with a long history of systemic use for acne, clindamycin, is also showing promising results in combination with benzoyl peroxide (1.2%/3.75% gel). A 12-week double-blind study of the combination, compared with vehicle alone for individuals with moderate or severe acne, showed significant improvement in comedonal and inflammatory lesions, as well as overall global improvement in severity, for the treatment arm, she said (J Drugs Dermatol. 2014 Sep;13[9]:1083-9).

Dr. Stein Gold reports being a consultant and investigator for Galderma, Stiefel Laboratories, and Allergan; a consultant and speaker for Valeant; a speaker for Ranbaxy Laboratories, Promius Pharma, and Actavis; and a medical/legal consultant for Roche.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – New acne treatment strategies that address the issue of antibiotic resistance include subantimicrobial dosing; new, narrower-spectrum antibiotics; and topical use of tetracycline-family antibiotics, according to Dr. Linda Stein Gold, a dermatologist at Henry Ford Hospital, Detroit.

Oral antibiotics have long been a mainstay of acne treatment, but long-term use of low-dose antibiotics may be contributing to the global crisis of antibiotic resistance. At least 2 million people become infected with resistant bacteria yearly in the United States alone, and at least 23,000 people die yearly from these infections, she noted.

“In dermatology we use antibiotics quite a bit, and we want to make sure when we’re utilizing drugs, we’re utilizing them in the best possible way,” Dr. Stein Gold said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. Finding the right antibiotic dose for effective treatment of acne can be a challenge, she noted. “Is more better? Is too little bad?”

In a review of new treatment strategies that address these concerns without compromising efficacy, Dr. Stein Gold said that the rationale for using subantimicrobial antibiotic dosing comes from the anti-inflammatory effect seen with many antibiotics, even with doses lower than needed for antimicrobial action.

For example, a study of a subantimicrobial-dose of doxycycline found that when adults with moderate acne were treated with the antibiotic (20 mg, twice daily) for 6 months, their acne significantly improved. The number of comedones, inflammatory lesions, and noninflammatory lesions improved significantly compared with those on placebo (Arch Dermatol. 2003 Apr; 139:459-64).

In another head-to-head trial that compared low-dose modified-release doxycycline with placebo or 100 mg of doxycycline, the lower dose outperformed both placebo and full-strength antibiotics. No resistant organisms were found among skin flora in the subjects, and the microbiota of the patients’ skin did not change significantly during the study period, she said.

Dr. Stein Gold’s work also suggests that systemic antibiotics may not be necessary for all patients with acne: In a study, after 12 weeks of treatment, adapalene plus benzoyl peroxide, in combination with doxycycline, resulted in significantly more patients with clear or almost-clear skin than with vehicle alone plus doxycycline. “Antibiotics are not always the golden nugget in the treatment of acne,” she commented.

Another tactic is to treat with antibiotics for a period of 3-6 months along with potent topicals, to get skin clear or almost clear, then discontinue the antibiotic and continue topical treatment. Many patients will be able to maintain clear skin on this regime, she noted.

A new tetracycline-family antibiotic, sarecycline, is in phase III trials for acne vulgaris and in phase II trials for acne rosacea. Sarecycline, “compared with existing tetracycline antibiotics, showed improved anti-inflammatory properties and a narrower spectrum of activity,” Dr. Stein Gold said.

A topical minocycline in a foam formulation shows promising results for tolerability and efficacy in phase II trials for moderate and severe acne, she added. Dapsone as a 7.5% topical gel formulation is in phase III clinical trials as well.

Another antibiotic with a long history of systemic use for acne, clindamycin, is also showing promising results in combination with benzoyl peroxide (1.2%/3.75% gel). A 12-week double-blind study of the combination, compared with vehicle alone for individuals with moderate or severe acne, showed significant improvement in comedonal and inflammatory lesions, as well as overall global improvement in severity, for the treatment arm, she said (J Drugs Dermatol. 2014 Sep;13[9]:1083-9).

Dr. Stein Gold reports being a consultant and investigator for Galderma, Stiefel Laboratories, and Allergan; a consultant and speaker for Valeant; a speaker for Ranbaxy Laboratories, Promius Pharma, and Actavis; and a medical/legal consultant for Roche.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

Long-term use of the blood-thinning agent clopidogrel did not alter the risk of death in people with heart disease or at risk of developing heart disease, nor did the drug appear to affect cancer risk, according to a statement from the U.S. Food and Drug Administration.

The FDA’s meta-analysis looked at results from 12 trials enrolling a total of 56,799 patients to evaluate the effect of long-term clopidogrel use on all-cause mortality. The incidence of all-cause mortality was 6.7% for the long-term clopidogrel plus aspirin arm and 6.6% for the comparator, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% confidence interval, –0.35%-0.44%).

“The results indicate that long-term (12 months or longer) dual-antiplatelet therapy with clopidogrel and aspirin do not appear to change the overall risk of death, compared with short-term (6 months or less) clopidogrel and aspirin, or aspirin alone,” the agency said in its statement.

The FDA also conducted a meta-analysis looking at nine of these trials (n = 45,374) that had enrolled patients with coronary artery disease or patients at risk of CAD. This also suggested no difference in the risk of all-cause mortality (MH RD –0.07%; 95% CI, –0.43%- 0.29%).

The meta-analysis included results from the Dual-Antiplatelet Therapy Trial (DAPT), whose results included a worrisome safety signal for extended use of clopidogrel (N Engl J Med 2014; 371:2155-66). Patients in the DAPT underwent percutaneous coronary intervention and placement of a drug-eluting stent, after which they received 1 year of clopidogrel or prasugrel plus aspirin. About 1,000 patients were then randomized to 18 additional months of one of the dual-antiplatelet therapies or to aspirin plus placebo. Extended (30-month) use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs. 1.5% for 12 months), whereas no increased risk was seen for prasugrel plus aspirin. A higher risk of death was mainly due to noncardiovascular causes, including cancer and trauma.

The DAPT did not show an increased risk of cancer-related adverse events related to treatment duration. However, the FDA performed two meta-analyses of other trials, with about 40,000 patients included in each analysis, to determine whether a signal could be found for either cancer-related adverse events or cancer-related death. Neither revealed an increased risk related to long-term clopidogrel use.

Long-term use of the blood-thinning agent clopidogrel did not alter the risk of death in people with heart disease or at risk of developing heart disease, nor did the drug appear to affect cancer risk, according to a statement from the U.S. Food and Drug Administration.

The FDA’s meta-analysis looked at results from 12 trials enrolling a total of 56,799 patients to evaluate the effect of long-term clopidogrel use on all-cause mortality. The incidence of all-cause mortality was 6.7% for the long-term clopidogrel plus aspirin arm and 6.6% for the comparator, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% confidence interval, –0.35%-0.44%).

“The results indicate that long-term (12 months or longer) dual-antiplatelet therapy with clopidogrel and aspirin do not appear to change the overall risk of death, compared with short-term (6 months or less) clopidogrel and aspirin, or aspirin alone,” the agency said in its statement.

The FDA also conducted a meta-analysis looking at nine of these trials (n = 45,374) that had enrolled patients with coronary artery disease or patients at risk of CAD. This also suggested no difference in the risk of all-cause mortality (MH RD –0.07%; 95% CI, –0.43%- 0.29%).

The meta-analysis included results from the Dual-Antiplatelet Therapy Trial (DAPT), whose results included a worrisome safety signal for extended use of clopidogrel (N Engl J Med 2014; 371:2155-66). Patients in the DAPT underwent percutaneous coronary intervention and placement of a drug-eluting stent, after which they received 1 year of clopidogrel or prasugrel plus aspirin. About 1,000 patients were then randomized to 18 additional months of one of the dual-antiplatelet therapies or to aspirin plus placebo. Extended (30-month) use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs. 1.5% for 12 months), whereas no increased risk was seen for prasugrel plus aspirin. A higher risk of death was mainly due to noncardiovascular causes, including cancer and trauma.

The DAPT did not show an increased risk of cancer-related adverse events related to treatment duration. However, the FDA performed two meta-analyses of other trials, with about 40,000 patients included in each analysis, to determine whether a signal could be found for either cancer-related adverse events or cancer-related death. Neither revealed an increased risk related to long-term clopidogrel use.

Long-term use of the blood-thinning agent clopidogrel did not alter the risk of death in people with heart disease or at risk of developing heart disease, nor did the drug appear to affect cancer risk, according to a statement from the U.S. Food and Drug Administration.

The FDA’s meta-analysis looked at results from 12 trials enrolling a total of 56,799 patients to evaluate the effect of long-term clopidogrel use on all-cause mortality. The incidence of all-cause mortality was 6.7% for the long-term clopidogrel plus aspirin arm and 6.6% for the comparator, resulting in a Mantel Haenszel Risk Difference (MH RD) of 0.04% (95% confidence interval, –0.35%-0.44%).

“The results indicate that long-term (12 months or longer) dual-antiplatelet therapy with clopidogrel and aspirin do not appear to change the overall risk of death, compared with short-term (6 months or less) clopidogrel and aspirin, or aspirin alone,” the agency said in its statement.

The FDA also conducted a meta-analysis looking at nine of these trials (n = 45,374) that had enrolled patients with coronary artery disease or patients at risk of CAD. This also suggested no difference in the risk of all-cause mortality (MH RD –0.07%; 95% CI, –0.43%- 0.29%).

The meta-analysis included results from the Dual-Antiplatelet Therapy Trial (DAPT), whose results included a worrisome safety signal for extended use of clopidogrel (N Engl J Med 2014; 371:2155-66). Patients in the DAPT underwent percutaneous coronary intervention and placement of a drug-eluting stent, after which they received 1 year of clopidogrel or prasugrel plus aspirin. About 1,000 patients were then randomized to 18 additional months of one of the dual-antiplatelet therapies or to aspirin plus placebo. Extended (30-month) use of clopidogrel plus aspirin was associated with a significantly increased risk of death (2.2% for 30 months vs. 1.5% for 12 months), whereas no increased risk was seen for prasugrel plus aspirin. A higher risk of death was mainly due to noncardiovascular causes, including cancer and trauma.

The DAPT did not show an increased risk of cancer-related adverse events related to treatment duration. However, the FDA performed two meta-analyses of other trials, with about 40,000 patients included in each analysis, to determine whether a signal could be found for either cancer-related adverse events or cancer-related death. Neither revealed an increased risk related to long-term clopidogrel use.

While smoking is linked to an increased risk of developing diabetes, this risk appears to drop over the long term once cigarette use stops, a review of evidence suggests.

Researchers analyzed data on almost 5.9 million people in 88 previous studies examining the connection between smoking, second-hand smoke exposure and diabetes. They estimated that roughly 28 million type 2 diabetes cases worldwide - or about 11.7 percent of cases in men and 2.4 percent in women - could be attributed to active smoking.

The more cigarettes smokers consumed, the more their odds of getting diabetes increased.

If they quit, ex-smokers initially faced an even higher risk of diabetes, but as more years pass without cigarette use their odds of getting the disease gradually diminished, the analysis found.

"The diabetes risk remains high in the recent quitters," said lead study author An Pan, of Huazhong University of Science and Technology in China. Weight gain linked to smoking cessation may be at least partly to blame for the heightened diabetes risk in those first months after giving up cigarettes, Pan added.

"However, the diabetes risk is reduced substantially after five years," Pan said by email. "The long-term benefits - including benefits for other diseases like cancer and heart disease - clearly outweigh the short-term higher risk."

Worldwide, nearly one in 10 adults had diabetes in 2014, and the disease will be the seventh leading cause of death by 2030, according to the World Health Organization.

Most of these people have type 2 diabetes, which is associated with obesity and aging and happens when the body can't properly use or make enough of the hormone insulin to convert blood sugar into energy. Left untreated, diabetes can lead to nerve damage, amputations, blindness, heart disease and strokes.

Plenty of research has established a connection between smoking and diabetes, although the reason is still unclear.

For the current analysis, Pan and colleges focused on exploring the link between the amount and type of smoke exposure and diabetes risk, as well as the potential for this risk to diminish with smoking cessation.

Overall, the pooled data from all the studies showed the risk of diabetes was 37 percent higher for smokers than non-smokers, the study team reports in The Lancet Diabetes and Endocrinology.

Exactly how smoking might lead to diabetes isn't firmly established, but it's possible smoking might cause inflammation, which in turn boosts the risk for diabetes, Dr. Abbas Dehghan, of Erasmus University Medical Center in Rotterdam, The Netherlands.

"The more one smokes, the more chronic inflammation there will be, and the higher the risk of diabetes will be," Dehghan, who wasn't involved in the study, said by email.

Occasional smokers were 21 percent more likely to have diabetes than people who never picked up the habit, while the increased risk was 57 percent for heavy smokers.

People exposed to second-hand smoke were 22 percent more likely to develop diabetes than people who never smoked, the study also found.

If smokers quit, their risk of diabetes over the next five years was 54 percent higher than for people who never smoked. After that, the increased risk dropped to 18 percent over the following five-year period. Remaining abstinent for a decade or more, however, reduced the extra risk to 11 percent.

While the connection between smoking and diabetes is nowhere near as strong as the link between cigarettes and lung cancer, the findings still suggest that doctors should add diabetes to the list of risks they warn smokers about, Amy Taylor of the University of Bristol in the U.K. and colleagues note in an accompanying editorial.

The short-term increase in diabetes risk after quitting shouldn't deter smokers' cessation efforts, they argue. Instead, smokers should remember that cigarettes are tied to lower weight and cessation can lead some people to eat or drink more, leading to weight gain.

While smoking is linked to an increased risk of developing diabetes, this risk appears to drop over the long term once cigarette use stops, a review of evidence suggests.

Researchers analyzed data on almost 5.9 million people in 88 previous studies examining the connection between smoking, second-hand smoke exposure and diabetes. They estimated that roughly 28 million type 2 diabetes cases worldwide - or about 11.7 percent of cases in men and 2.4 percent in women - could be attributed to active smoking.

The more cigarettes smokers consumed, the more their odds of getting diabetes increased.

If they quit, ex-smokers initially faced an even higher risk of diabetes, but as more years pass without cigarette use their odds of getting the disease gradually diminished, the analysis found.

"The diabetes risk remains high in the recent quitters," said lead study author An Pan, of Huazhong University of Science and Technology in China. Weight gain linked to smoking cessation may be at least partly to blame for the heightened diabetes risk in those first months after giving up cigarettes, Pan added.

"However, the diabetes risk is reduced substantially after five years," Pan said by email. "The long-term benefits - including benefits for other diseases like cancer and heart disease - clearly outweigh the short-term higher risk."

Worldwide, nearly one in 10 adults had diabetes in 2014, and the disease will be the seventh leading cause of death by 2030, according to the World Health Organization.

Most of these people have type 2 diabetes, which is associated with obesity and aging and happens when the body can't properly use or make enough of the hormone insulin to convert blood sugar into energy. Left untreated, diabetes can lead to nerve damage, amputations, blindness, heart disease and strokes.

Plenty of research has established a connection between smoking and diabetes, although the reason is still unclear.

For the current analysis, Pan and colleges focused on exploring the link between the amount and type of smoke exposure and diabetes risk, as well as the potential for this risk to diminish with smoking cessation.

Overall, the pooled data from all the studies showed the risk of diabetes was 37 percent higher for smokers than non-smokers, the study team reports in The Lancet Diabetes and Endocrinology.

Exactly how smoking might lead to diabetes isn't firmly established, but it's possible smoking might cause inflammation, which in turn boosts the risk for diabetes, Dr. Abbas Dehghan, of Erasmus University Medical Center in Rotterdam, The Netherlands.

"The more one smokes, the more chronic inflammation there will be, and the higher the risk of diabetes will be," Dehghan, who wasn't involved in the study, said by email.

Occasional smokers were 21 percent more likely to have diabetes than people who never picked up the habit, while the increased risk was 57 percent for heavy smokers.

People exposed to second-hand smoke were 22 percent more likely to develop diabetes than people who never smoked, the study also found.

If smokers quit, their risk of diabetes over the next five years was 54 percent higher than for people who never smoked. After that, the increased risk dropped to 18 percent over the following five-year period. Remaining abstinent for a decade or more, however, reduced the extra risk to 11 percent.

While the connection between smoking and diabetes is nowhere near as strong as the link between cigarettes and lung cancer, the findings still suggest that doctors should add diabetes to the list of risks they warn smokers about, Amy Taylor of the University of Bristol in the U.K. and colleagues note in an accompanying editorial.

The short-term increase in diabetes risk after quitting shouldn't deter smokers' cessation efforts, they argue. Instead, smokers should remember that cigarettes are tied to lower weight and cessation can lead some people to eat or drink more, leading to weight gain.

While smoking is linked to an increased risk of developing diabetes, this risk appears to drop over the long term once cigarette use stops, a review of evidence suggests.

Researchers analyzed data on almost 5.9 million people in 88 previous studies examining the connection between smoking, second-hand smoke exposure and diabetes. They estimated that roughly 28 million type 2 diabetes cases worldwide - or about 11.7 percent of cases in men and 2.4 percent in women - could be attributed to active smoking.

The more cigarettes smokers consumed, the more their odds of getting diabetes increased.

If they quit, ex-smokers initially faced an even higher risk of diabetes, but as more years pass without cigarette use their odds of getting the disease gradually diminished, the analysis found.

"The diabetes risk remains high in the recent quitters," said lead study author An Pan, of Huazhong University of Science and Technology in China. Weight gain linked to smoking cessation may be at least partly to blame for the heightened diabetes risk in those first months after giving up cigarettes, Pan added.

"However, the diabetes risk is reduced substantially after five years," Pan said by email. "The long-term benefits - including benefits for other diseases like cancer and heart disease - clearly outweigh the short-term higher risk."

Worldwide, nearly one in 10 adults had diabetes in 2014, and the disease will be the seventh leading cause of death by 2030, according to the World Health Organization.

Most of these people have type 2 diabetes, which is associated with obesity and aging and happens when the body can't properly use or make enough of the hormone insulin to convert blood sugar into energy. Left untreated, diabetes can lead to nerve damage, amputations, blindness, heart disease and strokes.

Plenty of research has established a connection between smoking and diabetes, although the reason is still unclear.

For the current analysis, Pan and colleges focused on exploring the link between the amount and type of smoke exposure and diabetes risk, as well as the potential for this risk to diminish with smoking cessation.

Overall, the pooled data from all the studies showed the risk of diabetes was 37 percent higher for smokers than non-smokers, the study team reports in The Lancet Diabetes and Endocrinology.

Exactly how smoking might lead to diabetes isn't firmly established, but it's possible smoking might cause inflammation, which in turn boosts the risk for diabetes, Dr. Abbas Dehghan, of Erasmus University Medical Center in Rotterdam, The Netherlands.

"The more one smokes, the more chronic inflammation there will be, and the higher the risk of diabetes will be," Dehghan, who wasn't involved in the study, said by email.

Occasional smokers were 21 percent more likely to have diabetes than people who never picked up the habit, while the increased risk was 57 percent for heavy smokers.

People exposed to second-hand smoke were 22 percent more likely to develop diabetes than people who never smoked, the study also found.

If smokers quit, their risk of diabetes over the next five years was 54 percent higher than for people who never smoked. After that, the increased risk dropped to 18 percent over the following five-year period. Remaining abstinent for a decade or more, however, reduced the extra risk to 11 percent.

While the connection between smoking and diabetes is nowhere near as strong as the link between cigarettes and lung cancer, the findings still suggest that doctors should add diabetes to the list of risks they warn smokers about, Amy Taylor of the University of Bristol in the U.K. and colleagues note in an accompanying editorial.

The short-term increase in diabetes risk after quitting shouldn't deter smokers' cessation efforts, they argue. Instead, smokers should remember that cigarettes are tied to lower weight and cessation can lead some people to eat or drink more, leading to weight gain.

Reflectance Confocal Microscopy (RCM) images of actinic keratoses (AKs) accord well with histopatholgy images, and trained dermatologists can readily distinguish different grades of cytological atypia in the lesions using RCM images alone, according to a report published in the November issue of Journal of the European Academy of Dermatology and Venereology.

RCM is a noninvasive optical technology that enhances clinical diagnostic accuracy, permitting clinicians to assess cytologic and architectural aspects of the epidermis in vivo. Researchers hypothesized that RCM could be used to grade AKs by allowing clinicians to assess “the irregularity of the honeycombed pattern reflecting the architectural disarray of the epidermal spinous layer,” said Dr. Giovanni Pellacani of the department of dermatology, University of Modena and Reggio Emilia, Modena, Italy, and his associates.

Future FamDoc/Wikimedia Commons/CC BY-SA 4.0/No changes

In a prospective study, two independent pathologists examined micrographs taken from punch biopsies and RCM images from 48 consecutive cases of facial/scalp AKs collected in a database; they also assessed two benign samples from one young patient with no sun-damaged skin and one elderly patient with severely sun-damaged skin, which served as the controls.

They graded the lesions/samples, classifying 38 as low- or moderate-grade AKs, 10 as high-grade AKs, and the two control samples as normal or lowest-grade sun-damaged skin.

Then three “raters” (two dermatopathologists and Dr. Pellacani) evaluated the RCM images, which showed a representative horizontal section of the epidermis at the stratum spinosum, while the two dermatopathologist raters evaluated photomicrographs taken at histopathology examination, grading the keratinocyte atypia they observed.

RCM grading of keratinocyte atypia strongly correlated among the three RCM raters, and the correlations were strongest for higher-grade lesions. Histopathologic grading also strongly correlated between two pathologist raters. Most important, grading of keratinocytic atypia strongly correlated between these two groups: Raters of the RCM images consistently distinguished different grades of atypia accurately.

These findings show that RCM can allow noninvasive in vivo assessment of keratinocyte morphology that is comparable to that obtained with invasive histopathology, the investigators concluded (J Eur Acad Dermatol Venereol. 2015;29[11]: 2216-21).

“RCM enables one to quickly explore several lesions and skin areas, offering a quasi-histological view of the epidermis useful for the study of AKs. This may lead, in the future, to the use of noninvasive technologies, such as RCM, for studying and monitoring of AKs and other diseases characterized by alterations of keratinocyte morphology thus avoiding the burden of invasive biopsies in clinical trials,” Dr. Pellacani and his associates said.

“Other advantages of noninvasive skin assessments are the possibility to evaluate a larger number of lesions and perilesional areas, and to collect dynamic information on quasi-histological changes occurring during the course of the disease, without alteration induced by the healing process following skin biopsy. This may also facilitate the evaluation of the efficacy of the treatments for AK and field cancerization at cellular level of keratinocytes,” they added.

Reflectance Confocal Microscopy (RCM) images of actinic keratoses (AKs) accord well with histopatholgy images, and trained dermatologists can readily distinguish different grades of cytological atypia in the lesions using RCM images alone, according to a report published in the November issue of Journal of the European Academy of Dermatology and Venereology.

RCM is a noninvasive optical technology that enhances clinical diagnostic accuracy, permitting clinicians to assess cytologic and architectural aspects of the epidermis in vivo. Researchers hypothesized that RCM could be used to grade AKs by allowing clinicians to assess “the irregularity of the honeycombed pattern reflecting the architectural disarray of the epidermal spinous layer,” said Dr. Giovanni Pellacani of the department of dermatology, University of Modena and Reggio Emilia, Modena, Italy, and his associates.

Future FamDoc/Wikimedia Commons/CC BY-SA 4.0/No changes

In a prospective study, two independent pathologists examined micrographs taken from punch biopsies and RCM images from 48 consecutive cases of facial/scalp AKs collected in a database; they also assessed two benign samples from one young patient with no sun-damaged skin and one elderly patient with severely sun-damaged skin, which served as the controls.

They graded the lesions/samples, classifying 38 as low- or moderate-grade AKs, 10 as high-grade AKs, and the two control samples as normal or lowest-grade sun-damaged skin.

Then three “raters” (two dermatopathologists and Dr. Pellacani) evaluated the RCM images, which showed a representative horizontal section of the epidermis at the stratum spinosum, while the two dermatopathologist raters evaluated photomicrographs taken at histopathology examination, grading the keratinocyte atypia they observed.

RCM grading of keratinocyte atypia strongly correlated among the three RCM raters, and the correlations were strongest for higher-grade lesions. Histopathologic grading also strongly correlated between two pathologist raters. Most important, grading of keratinocytic atypia strongly correlated between these two groups: Raters of the RCM images consistently distinguished different grades of atypia accurately.

These findings show that RCM can allow noninvasive in vivo assessment of keratinocyte morphology that is comparable to that obtained with invasive histopathology, the investigators concluded (J Eur Acad Dermatol Venereol. 2015;29[11]: 2216-21).

“RCM enables one to quickly explore several lesions and skin areas, offering a quasi-histological view of the epidermis useful for the study of AKs. This may lead, in the future, to the use of noninvasive technologies, such as RCM, for studying and monitoring of AKs and other diseases characterized by alterations of keratinocyte morphology thus avoiding the burden of invasive biopsies in clinical trials,” Dr. Pellacani and his associates said.

“Other advantages of noninvasive skin assessments are the possibility to evaluate a larger number of lesions and perilesional areas, and to collect dynamic information on quasi-histological changes occurring during the course of the disease, without alteration induced by the healing process following skin biopsy. This may also facilitate the evaluation of the efficacy of the treatments for AK and field cancerization at cellular level of keratinocytes,” they added.

Reflectance Confocal Microscopy (RCM) images of actinic keratoses (AKs) accord well with histopatholgy images, and trained dermatologists can readily distinguish different grades of cytological atypia in the lesions using RCM images alone, according to a report published in the November issue of Journal of the European Academy of Dermatology and Venereology.

RCM is a noninvasive optical technology that enhances clinical diagnostic accuracy, permitting clinicians to assess cytologic and architectural aspects of the epidermis in vivo. Researchers hypothesized that RCM could be used to grade AKs by allowing clinicians to assess “the irregularity of the honeycombed pattern reflecting the architectural disarray of the epidermal spinous layer,” said Dr. Giovanni Pellacani of the department of dermatology, University of Modena and Reggio Emilia, Modena, Italy, and his associates.

Future FamDoc/Wikimedia Commons/CC BY-SA 4.0/No changes

In a prospective study, two independent pathologists examined micrographs taken from punch biopsies and RCM images from 48 consecutive cases of facial/scalp AKs collected in a database; they also assessed two benign samples from one young patient with no sun-damaged skin and one elderly patient with severely sun-damaged skin, which served as the controls.

They graded the lesions/samples, classifying 38 as low- or moderate-grade AKs, 10 as high-grade AKs, and the two control samples as normal or lowest-grade sun-damaged skin.

Then three “raters” (two dermatopathologists and Dr. Pellacani) evaluated the RCM images, which showed a representative horizontal section of the epidermis at the stratum spinosum, while the two dermatopathologist raters evaluated photomicrographs taken at histopathology examination, grading the keratinocyte atypia they observed.

RCM grading of keratinocyte atypia strongly correlated among the three RCM raters, and the correlations were strongest for higher-grade lesions. Histopathologic grading also strongly correlated between two pathologist raters. Most important, grading of keratinocytic atypia strongly correlated between these two groups: Raters of the RCM images consistently distinguished different grades of atypia accurately.

These findings show that RCM can allow noninvasive in vivo assessment of keratinocyte morphology that is comparable to that obtained with invasive histopathology, the investigators concluded (J Eur Acad Dermatol Venereol. 2015;29[11]: 2216-21).

“RCM enables one to quickly explore several lesions and skin areas, offering a quasi-histological view of the epidermis useful for the study of AKs. This may lead, in the future, to the use of noninvasive technologies, such as RCM, for studying and monitoring of AKs and other diseases characterized by alterations of keratinocyte morphology thus avoiding the burden of invasive biopsies in clinical trials,” Dr. Pellacani and his associates said.

“Other advantages of noninvasive skin assessments are the possibility to evaluate a larger number of lesions and perilesional areas, and to collect dynamic information on quasi-histological changes occurring during the course of the disease, without alteration induced by the healing process following skin biopsy. This may also facilitate the evaluation of the efficacy of the treatments for AK and field cancerization at cellular level of keratinocytes,” they added.

LAS VEGAS – Tinea pedis plagues millions of patients yearly, and treatment is lengthy, cumbersome, and often ineffective.

But two potent new antifungals promise an easier treatment regimen and a higher rate of successful treatment outcomes, according to Dr. David M. Pariser, who shared data about luliconazole and a new formulation of naftifine as topical treatments for tinea infections, at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Dr. Pariser, professor in the department of dermatology at Eastern Virginia Medical School, Norfolk, pointed out that most antifungals currently approved for tinea pedis require at least daily – and sometimes twice daily – application for at least 4 weeks. Terbinafine and tolnaftate are the exceptions, with treatment periods ranging from 1-6 weeks for the two products, depending on clinical response.

A new formulation of naftifine hydrochloride 2%, (Naftin), a potent prescription topical allylamine antifungal available as a cream or a gel, has shown equivalent efficacy with just two weeks of treatment. Naftifine has lipophilic and keratinophilic properties; further, it has clinically significant anti-inflammatory and antibacterial effects, in addition to its potent fungicidal and fungistatic effects against dermatophytes, Dr. Pariser said at the meeting. The preparations are currently approved for topical treatment of tinea pedis, tinea cruris, and tinea corporis.

Notably, naftifine maintains a “clinically relevant therapeutic reservoir effect after treatment completion, with naftifine detected in the stratum corneum for up to 4 weeks posttreatment,” he said. This reservoir effect permits a significantly easier treatment regimen, with topical application of either formulation daily for just 2 weeks.

The clinical trials of naftifine HCl 2% with daily administration for 2 weeks showed equivalence with the 1% formulation administered for 4 weeks; the higher concentration was well tolerated and was effective in both the moccasin and interdigital distributions of tinea pedis involvement. Trials also showed the mycologic and clinical cure rates of naftifine 2% to be equivalent or superior to those of terbinafine, econazole, clotrimazole, miconazole, and tolnaftate.

Clinical trials showed treatment effectiveness – defined as 90% improvement over baseline and achieving “essentially normal skin” – in 52% of patients receiving naftifine 2%, compared with 20% of patients receiving vehicle only. Overall clinical success – defined as mycologic cure and either clinical cure of effective clinical treatment – was seen in 78% of the naftifine 2% patients, compared with 49% of the vehicle patients.

The second antifungal Dr. Pariser discussed is luliconazole (Luzu), a prescription topical imidazole that is available as a 1% cream. Luliconazole is also a broad-spectrum, potent antifungal with effects that persist several weeks after treatment. The preparation is at least as effective as bifonazole, terbinafine, and lanoconazole, both in vitro and in vivo, Dr. Pariser said.

In two parallel clinical trials comparing luliconazole 1% cream to its vehicle, treatment was effective (at least 90% clearing and with normal-appearing skin) in 48% and 33% of patients receiving luliconazole, compared with 10% and 15% of patients receiving vehicle alone.

An advantage of the topical agents is that there are generally no major systemic side effects, since there is minimal systemic absorption, Dr. Pariser noted. Allergic contact dermatitis may be a local reaction, but tends to be mild and transient, he said.

Clinicians should always be alert for tinea pedis when treating onychomycosis, said Dr. Pariser, and untreated tinea can contribute to recurrence of nail fungus. “If you don’t look for tinea, you might not find it, and you’ve missed a treatment opportunity,” he said.

Dr. Pariser disclosed that he is an investigator and consultant for Valeant and an investigator for Anacor Pharmaceuticals.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Tinea pedis plagues millions of patients yearly, and treatment is lengthy, cumbersome, and often ineffective.

But two potent new antifungals promise an easier treatment regimen and a higher rate of successful treatment outcomes, according to Dr. David M. Pariser, who shared data about luliconazole and a new formulation of naftifine as topical treatments for tinea infections, at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Dr. Pariser, professor in the department of dermatology at Eastern Virginia Medical School, Norfolk, pointed out that most antifungals currently approved for tinea pedis require at least daily – and sometimes twice daily – application for at least 4 weeks. Terbinafine and tolnaftate are the exceptions, with treatment periods ranging from 1-6 weeks for the two products, depending on clinical response.

A new formulation of naftifine hydrochloride 2%, (Naftin), a potent prescription topical allylamine antifungal available as a cream or a gel, has shown equivalent efficacy with just two weeks of treatment. Naftifine has lipophilic and keratinophilic properties; further, it has clinically significant anti-inflammatory and antibacterial effects, in addition to its potent fungicidal and fungistatic effects against dermatophytes, Dr. Pariser said at the meeting. The preparations are currently approved for topical treatment of tinea pedis, tinea cruris, and tinea corporis.

Notably, naftifine maintains a “clinically relevant therapeutic reservoir effect after treatment completion, with naftifine detected in the stratum corneum for up to 4 weeks posttreatment,” he said. This reservoir effect permits a significantly easier treatment regimen, with topical application of either formulation daily for just 2 weeks.

The clinical trials of naftifine HCl 2% with daily administration for 2 weeks showed equivalence with the 1% formulation administered for 4 weeks; the higher concentration was well tolerated and was effective in both the moccasin and interdigital distributions of tinea pedis involvement. Trials also showed the mycologic and clinical cure rates of naftifine 2% to be equivalent or superior to those of terbinafine, econazole, clotrimazole, miconazole, and tolnaftate.

Clinical trials showed treatment effectiveness – defined as 90% improvement over baseline and achieving “essentially normal skin” – in 52% of patients receiving naftifine 2%, compared with 20% of patients receiving vehicle only. Overall clinical success – defined as mycologic cure and either clinical cure of effective clinical treatment – was seen in 78% of the naftifine 2% patients, compared with 49% of the vehicle patients.

The second antifungal Dr. Pariser discussed is luliconazole (Luzu), a prescription topical imidazole that is available as a 1% cream. Luliconazole is also a broad-spectrum, potent antifungal with effects that persist several weeks after treatment. The preparation is at least as effective as bifonazole, terbinafine, and lanoconazole, both in vitro and in vivo, Dr. Pariser said.

In two parallel clinical trials comparing luliconazole 1% cream to its vehicle, treatment was effective (at least 90% clearing and with normal-appearing skin) in 48% and 33% of patients receiving luliconazole, compared with 10% and 15% of patients receiving vehicle alone.

An advantage of the topical agents is that there are generally no major systemic side effects, since there is minimal systemic absorption, Dr. Pariser noted. Allergic contact dermatitis may be a local reaction, but tends to be mild and transient, he said.

Clinicians should always be alert for tinea pedis when treating onychomycosis, said Dr. Pariser, and untreated tinea can contribute to recurrence of nail fungus. “If you don’t look for tinea, you might not find it, and you’ve missed a treatment opportunity,” he said.

Dr. Pariser disclosed that he is an investigator and consultant for Valeant and an investigator for Anacor Pharmaceuticals.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Tinea pedis plagues millions of patients yearly, and treatment is lengthy, cumbersome, and often ineffective.

But two potent new antifungals promise an easier treatment regimen and a higher rate of successful treatment outcomes, according to Dr. David M. Pariser, who shared data about luliconazole and a new formulation of naftifine as topical treatments for tinea infections, at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Dr. Pariser, professor in the department of dermatology at Eastern Virginia Medical School, Norfolk, pointed out that most antifungals currently approved for tinea pedis require at least daily – and sometimes twice daily – application for at least 4 weeks. Terbinafine and tolnaftate are the exceptions, with treatment periods ranging from 1-6 weeks for the two products, depending on clinical response.

A new formulation of naftifine hydrochloride 2%, (Naftin), a potent prescription topical allylamine antifungal available as a cream or a gel, has shown equivalent efficacy with just two weeks of treatment. Naftifine has lipophilic and keratinophilic properties; further, it has clinically significant anti-inflammatory and antibacterial effects, in addition to its potent fungicidal and fungistatic effects against dermatophytes, Dr. Pariser said at the meeting. The preparations are currently approved for topical treatment of tinea pedis, tinea cruris, and tinea corporis.

Notably, naftifine maintains a “clinically relevant therapeutic reservoir effect after treatment completion, with naftifine detected in the stratum corneum for up to 4 weeks posttreatment,” he said. This reservoir effect permits a significantly easier treatment regimen, with topical application of either formulation daily for just 2 weeks.

The clinical trials of naftifine HCl 2% with daily administration for 2 weeks showed equivalence with the 1% formulation administered for 4 weeks; the higher concentration was well tolerated and was effective in both the moccasin and interdigital distributions of tinea pedis involvement. Trials also showed the mycologic and clinical cure rates of naftifine 2% to be equivalent or superior to those of terbinafine, econazole, clotrimazole, miconazole, and tolnaftate.

Clinical trials showed treatment effectiveness – defined as 90% improvement over baseline and achieving “essentially normal skin” – in 52% of patients receiving naftifine 2%, compared with 20% of patients receiving vehicle only. Overall clinical success – defined as mycologic cure and either clinical cure of effective clinical treatment – was seen in 78% of the naftifine 2% patients, compared with 49% of the vehicle patients.

The second antifungal Dr. Pariser discussed is luliconazole (Luzu), a prescription topical imidazole that is available as a 1% cream. Luliconazole is also a broad-spectrum, potent antifungal with effects that persist several weeks after treatment. The preparation is at least as effective as bifonazole, terbinafine, and lanoconazole, both in vitro and in vivo, Dr. Pariser said.

In two parallel clinical trials comparing luliconazole 1% cream to its vehicle, treatment was effective (at least 90% clearing and with normal-appearing skin) in 48% and 33% of patients receiving luliconazole, compared with 10% and 15% of patients receiving vehicle alone.

An advantage of the topical agents is that there are generally no major systemic side effects, since there is minimal systemic absorption, Dr. Pariser noted. Allergic contact dermatitis may be a local reaction, but tends to be mild and transient, he said.

Clinicians should always be alert for tinea pedis when treating onychomycosis, said Dr. Pariser, and untreated tinea can contribute to recurrence of nail fungus. “If you don’t look for tinea, you might not find it, and you’ve missed a treatment opportunity,” he said.

Dr. Pariser disclosed that he is an investigator and consultant for Valeant and an investigator for Anacor Pharmaceuticals.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

Apheresis donation

Photo by ec-jpr

ANAHEIM, CA—A newer, more streamlined apheresis system yields more CD34+ cells from stem cell transplant donors than a previous system, according to a new study.

Researchers used both tools—the COBE Spectra Apheresis System and the Spectra Optia Apheresis System—to collect mononuclear cells (MNCs) from healthy donors and found the collection efficiency and yield was superior with the Spectra Optia.

There were no unanticipated or serious adverse events with either system, and the frequency of treatment-emergent adverse events did not differ according to the system used.

Jose A. Cancelas, MD, PhD, of Hoxworth Blood Center in Cincinnati, Ohio, presented the results of this research at the 2015 AABB Annual Meeting (abstract S21-020A). The study was supported by Terumo BCT, the company that makes both systems.

The COBE Spectra Apheresis System collects MNCs via single-step processing and separation. It has been the gold standard for hematopoietic stem and progenitor cell collection since 1987, Dr Cancelas noted.

The newer Spectra Optia Apheresis System uses optical sensors for tracking the separation process and real-time electronic adjustment of plasma pump velocity (automatic interface management). A single-step, continuous MNC collection (CMNC) protocol, which was recently approved for use with this system in the US, is intended to increase automation and MNC collection reproducibility.

To compare the 2 systems, Dr Cancelas and his colleagues conducted a prospective, randomized, crossover study of 22 healthy donors. They had a mean age of 35 and a mean body mass index of 34.2 kg/m².

The donors underwent 2 MNC collections, first with one apheresis system and then the other. Both times, the donors underwent apheresis on Days 5 and 6 after standard MNC mobilization with granulocyte colony-stimulating factor (G-CSF at 10 mg/kg/day) through Day 5. After the first collection, there was a 2-week washout period.

The study’s primary endpoint was CD34+ cell collection efficiency, which was the percentage of cells collected using the averaged pre/post-collection cell counts as the denominator (CE1). The secondary endpoint was also CD34+ cell collection efficiency, but this was the percentage of cells collected using only the pre-collection cell count as a denominator (CE2).

The researchers also assessed the CD34+ cell yield (CD34+ cells/kg), MNC product contamination/purity, procedure time, product volume, the need for operator involvement, and safety.

Results

All collections processed 1.5 times the total blood volume, and the procedures took nearly 2.5 hours, with no real time difference between the 2 systems.

The average flow rates were 66 mL/minute with the Spectra Optia and 68 mL/minute with COBE Spectra. Product volumes were 143 mL and 139 mL, respectively.

The Optia proved significantly superior to the COBE system with regard to CE1, CE2, and the CD34+ yield.

The mean CD34+ CE1 was 85% with Optia and 66.2% with COBE (P<0.001). The mean CD34+ CE2 was 62% and 48.4%, respectively (P<0.001). And the mean CD34+ yield (cells/kg) was 4.5 and 3.58, respectively (P=0.001).

In addition, granulocyte contamination was lower with the Optia system than the COBE system. The mean granulocyte yield was 7.7 x10⁹ and 10.6 x10⁹ granulocytes per unit, respectively (P=0.022).

However, red blood cell and platelet contaminations were similar between the systems. The mean red blood cell volume was 7.4 mL with Optia and 7.0 mL with COBE (P=0.660). And the mean platelet yield was 4.3 x10¹¹ and 4.6 x10¹¹, respectively (P=0.081).

Overall, there was no significant difference between the Optia and COBE systems in the need for operator adjustments, although there was a trend toward fewer adjustments with the Optia system. It required a median of 5.5 adjustments (range, 0-12), and the COBE system required a median of 6.5 adjustments (range, 1-14).

Dr Cancelas said the frequency of treatment-emergent adverse events did not differ according to the system used. And there were no unanticipated or serious adverse events.

The most frequently reported pre-collection treatment-emergent adverse events were back pain (n=10, 44%), bone pain (n=9, 39%), and fatigue (n=5, 22%).

“These results demonstrate that the Optia CMNC procedure is a safe and efficient means of collecting CD34+ cells in G-CSF mobilized donors,” Dr Cancelas said.

“The Optia collection efficiencies for CD34+ cells were significantly superior to the COBE . . . . And the Optia with automatic interface management system represents a technological advance in our ability to collect CD34+ cells.”

Apheresis donation

Photo by ec-jpr

ANAHEIM, CA—A newer, more streamlined apheresis system yields more CD34+ cells from stem cell transplant donors than a previous system, according to a new study.

Researchers used both tools—the COBE Spectra Apheresis System and the Spectra Optia Apheresis System—to collect mononuclear cells (MNCs) from healthy donors and found the collection efficiency and yield was superior with the Spectra Optia.

There were no unanticipated or serious adverse events with either system, and the frequency of treatment-emergent adverse events did not differ according to the system used.

Jose A. Cancelas, MD, PhD, of Hoxworth Blood Center in Cincinnati, Ohio, presented the results of this research at the 2015 AABB Annual Meeting (abstract S21-020A). The study was supported by Terumo BCT, the company that makes both systems.

The COBE Spectra Apheresis System collects MNCs via single-step processing and separation. It has been the gold standard for hematopoietic stem and progenitor cell collection since 1987, Dr Cancelas noted.

The newer Spectra Optia Apheresis System uses optical sensors for tracking the separation process and real-time electronic adjustment of plasma pump velocity (automatic interface management). A single-step, continuous MNC collection (CMNC) protocol, which was recently approved for use with this system in the US, is intended to increase automation and MNC collection reproducibility.

To compare the 2 systems, Dr Cancelas and his colleagues conducted a prospective, randomized, crossover study of 22 healthy donors. They had a mean age of 35 and a mean body mass index of 34.2 kg/m².

The donors underwent 2 MNC collections, first with one apheresis system and then the other. Both times, the donors underwent apheresis on Days 5 and 6 after standard MNC mobilization with granulocyte colony-stimulating factor (G-CSF at 10 mg/kg/day) through Day 5. After the first collection, there was a 2-week washout period.

The study’s primary endpoint was CD34+ cell collection efficiency, which was the percentage of cells collected using the averaged pre/post-collection cell counts as the denominator (CE1). The secondary endpoint was also CD34+ cell collection efficiency, but this was the percentage of cells collected using only the pre-collection cell count as a denominator (CE2).

The researchers also assessed the CD34+ cell yield (CD34+ cells/kg), MNC product contamination/purity, procedure time, product volume, the need for operator involvement, and safety.

Results

All collections processed 1.5 times the total blood volume, and the procedures took nearly 2.5 hours, with no real time difference between the 2 systems.

The average flow rates were 66 mL/minute with the Spectra Optia and 68 mL/minute with COBE Spectra. Product volumes were 143 mL and 139 mL, respectively.

The Optia proved significantly superior to the COBE system with regard to CE1, CE2, and the CD34+ yield.

The mean CD34+ CE1 was 85% with Optia and 66.2% with COBE (P<0.001). The mean CD34+ CE2 was 62% and 48.4%, respectively (P<0.001). And the mean CD34+ yield (cells/kg) was 4.5 and 3.58, respectively (P=0.001).

In addition, granulocyte contamination was lower with the Optia system than the COBE system. The mean granulocyte yield was 7.7 x10⁹ and 10.6 x10⁹ granulocytes per unit, respectively (P=0.022).

However, red blood cell and platelet contaminations were similar between the systems. The mean red blood cell volume was 7.4 mL with Optia and 7.0 mL with COBE (P=0.660). And the mean platelet yield was 4.3 x10¹¹ and 4.6 x10¹¹, respectively (P=0.081).

Overall, there was no significant difference between the Optia and COBE systems in the need for operator adjustments, although there was a trend toward fewer adjustments with the Optia system. It required a median of 5.5 adjustments (range, 0-12), and the COBE system required a median of 6.5 adjustments (range, 1-14).

Dr Cancelas said the frequency of treatment-emergent adverse events did not differ according to the system used. And there were no unanticipated or serious adverse events.

The most frequently reported pre-collection treatment-emergent adverse events were back pain (n=10, 44%), bone pain (n=9, 39%), and fatigue (n=5, 22%).

“These results demonstrate that the Optia CMNC procedure is a safe and efficient means of collecting CD34+ cells in G-CSF mobilized donors,” Dr Cancelas said.

“The Optia collection efficiencies for CD34+ cells were significantly superior to the COBE . . . . And the Optia with automatic interface management system represents a technological advance in our ability to collect CD34+ cells.”

Apheresis donation

Photo by ec-jpr

ANAHEIM, CA—A newer, more streamlined apheresis system yields more CD34+ cells from stem cell transplant donors than a previous system, according to a new study.

Researchers used both tools—the COBE Spectra Apheresis System and the Spectra Optia Apheresis System—to collect mononuclear cells (MNCs) from healthy donors and found the collection efficiency and yield was superior with the Spectra Optia.

There were no unanticipated or serious adverse events with either system, and the frequency of treatment-emergent adverse events did not differ according to the system used.

Jose A. Cancelas, MD, PhD, of Hoxworth Blood Center in Cincinnati, Ohio, presented the results of this research at the 2015 AABB Annual Meeting (abstract S21-020A). The study was supported by Terumo BCT, the company that makes both systems.

The COBE Spectra Apheresis System collects MNCs via single-step processing and separation. It has been the gold standard for hematopoietic stem and progenitor cell collection since 1987, Dr Cancelas noted.

The newer Spectra Optia Apheresis System uses optical sensors for tracking the separation process and real-time electronic adjustment of plasma pump velocity (automatic interface management). A single-step, continuous MNC collection (CMNC) protocol, which was recently approved for use with this system in the US, is intended to increase automation and MNC collection reproducibility.

To compare the 2 systems, Dr Cancelas and his colleagues conducted a prospective, randomized, crossover study of 22 healthy donors. They had a mean age of 35 and a mean body mass index of 34.2 kg/m².

The donors underwent 2 MNC collections, first with one apheresis system and then the other. Both times, the donors underwent apheresis on Days 5 and 6 after standard MNC mobilization with granulocyte colony-stimulating factor (G-CSF at 10 mg/kg/day) through Day 5. After the first collection, there was a 2-week washout period.

The study’s primary endpoint was CD34+ cell collection efficiency, which was the percentage of cells collected using the averaged pre/post-collection cell counts as the denominator (CE1). The secondary endpoint was also CD34+ cell collection efficiency, but this was the percentage of cells collected using only the pre-collection cell count as a denominator (CE2).

The researchers also assessed the CD34+ cell yield (CD34+ cells/kg), MNC product contamination/purity, procedure time, product volume, the need for operator involvement, and safety.

Results

All collections processed 1.5 times the total blood volume, and the procedures took nearly 2.5 hours, with no real time difference between the 2 systems.

The average flow rates were 66 mL/minute with the Spectra Optia and 68 mL/minute with COBE Spectra. Product volumes were 143 mL and 139 mL, respectively.

The Optia proved significantly superior to the COBE system with regard to CE1, CE2, and the CD34+ yield.

The mean CD34+ CE1 was 85% with Optia and 66.2% with COBE (P<0.001). The mean CD34+ CE2 was 62% and 48.4%, respectively (P<0.001). And the mean CD34+ yield (cells/kg) was 4.5 and 3.58, respectively (P=0.001).

In addition, granulocyte contamination was lower with the Optia system than the COBE system. The mean granulocyte yield was 7.7 x10⁹ and 10.6 x10⁹ granulocytes per unit, respectively (P=0.022).

However, red blood cell and platelet contaminations were similar between the systems. The mean red blood cell volume was 7.4 mL with Optia and 7.0 mL with COBE (P=0.660). And the mean platelet yield was 4.3 x10¹¹ and 4.6 x10¹¹, respectively (P=0.081).

Overall, there was no significant difference between the Optia and COBE systems in the need for operator adjustments, although there was a trend toward fewer adjustments with the Optia system. It required a median of 5.5 adjustments (range, 0-12), and the COBE system required a median of 6.5 adjustments (range, 1-14).

Dr Cancelas said the frequency of treatment-emergent adverse events did not differ according to the system used. And there were no unanticipated or serious adverse events.

The most frequently reported pre-collection treatment-emergent adverse events were back pain (n=10, 44%), bone pain (n=9, 39%), and fatigue (n=5, 22%).

“These results demonstrate that the Optia CMNC procedure is a safe and efficient means of collecting CD34+ cells in G-CSF mobilized donors,” Dr Cancelas said.

“The Optia collection efficiencies for CD34+ cells were significantly superior to the COBE . . . . And the Optia with automatic interface management system represents a technological advance in our ability to collect CD34+ cells.”