Kate Johnson

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.

MONTREAL — Topical 5-fluorouracil used for the treatment of actinic keratosis can also promote dermal remodeling in photoaged skin, according to a small study.

For years, clinicians and patients have noted that, in addition to treating actinic keratosis (AK), topical 5-fluorouracil (5-FU) treatment can result in skin softening and smoothing, Dr. Sewon Kang of Johns Hopkins University, Baltimore, said at the annual meeting of the Society for Investigative Dermatology.

"We knew this anecdotally, but it had never been documented or studied at a molecular level," he said in an interview. "We did this study to confirm people's clinical observation that this happens, and added a few lab measurements to support how it might be happening."

The nonrandomized, non-vehicle-controlled study was funded by Valeant Pharmaceuticals, and Dr. Kang did not disclose any conflicts of interest.

The study included 21 subjects, aged 56–85 years, who received 5% topical 5-FU cream twice daily for 2 weeks for the treatment of facial AK. In addition to AK lesions, all patients had moderate to severe photodamage.

The subjects underwent a baseline clinical skin examination, which was repeated 1 day after the last treatment application and again at 4, 10, and 24 weeks post treatment.

Photographic evaluation was performed, and photoaging parameters were assessed according to a photonumeric scale that included wrinkling, roughness, lentigines, hyperpigmentation, and sallowness. Biopsies were also taken at the same time points.

At the end of the study, the number of AKs was reduced from almost 12 to less than 2 per patient. In addition, photoaging scores dropped from slightly less than 5.5 to about 4.6, he reported.

Biopsies were used to examine the molecular end points of epidermal injury, inflammation, dermal matrix degradation, and collagen, Dr. Kang said.

"Epidermal injury causes an inflammatory reaction in the skin, which triggers collagen repair, and we believe this is the mechanism by which topical 5-FU might improve wrinkles," he explained at the meeting.

Biopsies taken at the end of the study showed a seven-fold increase from baseline in keratin 16, a marker of epidermal injury, and a two-fold increase in inflammatory cytokine expression. Additionally, there was a statistically significant increase in the induction of collagenase (MMP-1) and stromelysin (MMP-3), markers of dermal matrix degradation, he said.

Finally, procollagen protein levels increased significantly from baseline, indicating collagen repair.

"Topical 5-FU induces epidermal wounding by a mechanism similar to microdermabrasion and certain lasers used for the treatment of photoaging. Agents that produce irritation could improve photoaging," Dr. Kang concluded.

MONTREAL — The incidence of melanoma in the United States increased rapidly over a 10-year period, regardless of tumor thickness and socioeconomic status, reported Dr. Eleni Linos.

"This has implications for preventive screening and primary care," she said at the annual meeting of the Society for Investigative Dermatology.

Dr. Linos and her coinvestigators examined data from the Surveillance, Epidemiology, and End Results (SEER) registry between 1992 and 2004 (J. Invest. Derm. 2009 Jan. 8 [doi:10.1038/jid.2008.423

During the study period, the incidence of melanoma of all thicknesses increased from 18 per 100,000 in 1992 to 26 per 100,000 in 2004—an annual increase of 3%, said Dr. Linos of Stanford (Calif.) University. The steepest increase was seen in men aged 65 years and older, in whom the incidence rose from 73 to 126 new cases per 100,000. "The vast majority of melanomas that are diagnosed are thin, and that is why we have not seen such a dramatic increase in mortality rates," she explained. Overall mortality rose by 0.4% annually.

Melanoma trends were examined according to socioeconomic status to determine whether the findings could be explained by better screening in those with a higher status. Similarly, tumor thickness was examined to determine whether the increased incidence could be explained by more diagnoses of thin, clinically insignificant tumors.

"We found parallel increases across all socioeconomic groups and thicknesses, representing a true increase in clinically significant tumors," she said.

MONTREAL — The incidence of melanoma in the United States increased rapidly over a 10-year period, regardless of tumor thickness and socioeconomic status, reported Dr. Eleni Linos.

"This has implications for preventive screening and primary care," she said at the annual meeting of the Society for Investigative Dermatology.

Dr. Linos and her coinvestigators examined data from the Surveillance, Epidemiology, and End Results (SEER) registry between 1992 and 2004 (J. Invest. Derm. 2009 Jan. 8 [doi:10.1038/jid.2008.423

During the study period, the incidence of melanoma of all thicknesses increased from 18 per 100,000 in 1992 to 26 per 100,000 in 2004—an annual increase of 3%, said Dr. Linos of Stanford (Calif.) University. The steepest increase was seen in men aged 65 years and older, in whom the incidence rose from 73 to 126 new cases per 100,000. "The vast majority of melanomas that are diagnosed are thin, and that is why we have not seen such a dramatic increase in mortality rates," she explained. Overall mortality rose by 0.4% annually.

Melanoma trends were examined according to socioeconomic status to determine whether the findings could be explained by better screening in those with a higher status. Similarly, tumor thickness was examined to determine whether the increased incidence could be explained by more diagnoses of thin, clinically insignificant tumors.

"We found parallel increases across all socioeconomic groups and thicknesses, representing a true increase in clinically significant tumors," she said.

MONTREAL — The incidence of melanoma in the United States increased rapidly over a 10-year period, regardless of tumor thickness and socioeconomic status, reported Dr. Eleni Linos.

"This has implications for preventive screening and primary care," she said at the annual meeting of the Society for Investigative Dermatology.

Dr. Linos and her coinvestigators examined data from the Surveillance, Epidemiology, and End Results (SEER) registry between 1992 and 2004 (J. Invest. Derm. 2009 Jan. 8 [doi:10.1038/jid.2008.423

During the study period, the incidence of melanoma of all thicknesses increased from 18 per 100,000 in 1992 to 26 per 100,000 in 2004—an annual increase of 3%, said Dr. Linos of Stanford (Calif.) University. The steepest increase was seen in men aged 65 years and older, in whom the incidence rose from 73 to 126 new cases per 100,000. "The vast majority of melanomas that are diagnosed are thin, and that is why we have not seen such a dramatic increase in mortality rates," she explained. Overall mortality rose by 0.4% annually.

Melanoma trends were examined according to socioeconomic status to determine whether the findings could be explained by better screening in those with a higher status. Similarly, tumor thickness was examined to determine whether the increased incidence could be explained by more diagnoses of thin, clinically insignificant tumors.

"We found parallel increases across all socioeconomic groups and thicknesses, representing a true increase in clinically significant tumors," she said.

MONTREAL — Actinic keratoses are dynamic lesions and their expression varies over time, based on the results of an 11-month study of the natural course of the lesions in people with extensive actinic damage.

"At any one time, less than half of the lesions are evident clinically," said Dr. Craig Elmets, who reported his findings at the annual meeting of the Society for Investigative Dermatology.

The pattern of regression and recurrence of actinic keratoses (AK) has implications for the treatment of the lesions, said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

"If one is going to treat individual lesions, then they need to be treated aggressively because at any one time only a minority of the [visible] AKs are present," he said. "In patients with extensive actinic damage, peel treatment may be a very good approach to treating these lesions."

Dr. Elmets did not disclose any conflicts of interest in regard to this study, but he serves on the advisory boards of several pharmaceutical companies.

The study followed AK lesions for 11 months in 26 individuals with extensive actinic damage.

At baseline, the subjects had 10–40 actinic lesions and at least one prior histological diagnosis of an AK or a nonmelanoma skin cancer.

The subjects' AKs were mapped at baseline and again at 3, 6, 9, and 11 months.

The lesions also were biopsied at baseline and the end of the study. "If a lesion that had been selected for biopsy was no longer present clinically, the site where it had been was still biopsied," Dr. Elmets explained.

At baseline, there were a total of 610 AKs in the study group (mean 23.5 per individual). At the end of the study, this number was not significantly different despite the development of 973 new lesions over the 11-month period.

About 40% of the lesions present at baseline had regressed by month 11, and nearly 200 of the lesions that were present at baseline regressed and then recurred, he said. "A total of 51 of the lesions regressed twice."

Using a histologic grading scheme that was based on a cervical dysplasia model, Dr. Elmets noted little progression in the severity of lesions in terms of proliferation, atypia, or both features. "The histologic appearance seems to accurately correlate with the clinical appearance, and over the course of 11 months there was little evidence of histologic progression."

AKs have been thought to be precursors to squamous cell carcinomas in some cases.

The presence of AKs is strongly predictive of individuals who are at increased risk for basal cell and squamous cell carcinomas, noted Dr. Elmets.

The pattern of regression and recurrence of actinic keratoses may have implications for the treatment of the lesions. Courtesy Dr. Roger I. Ceilley

MONTREAL — Actinic keratoses are dynamic lesions and their expression varies over time, based on the results of an 11-month study of the natural course of the lesions in people with extensive actinic damage.

"At any one time, less than half of the lesions are evident clinically," said Dr. Craig Elmets, who reported his findings at the annual meeting of the Society for Investigative Dermatology.

The pattern of regression and recurrence of actinic keratoses (AK) has implications for the treatment of the lesions, said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

"If one is going to treat individual lesions, then they need to be treated aggressively because at any one time only a minority of the [visible] AKs are present," he said. "In patients with extensive actinic damage, peel treatment may be a very good approach to treating these lesions."

Dr. Elmets did not disclose any conflicts of interest in regard to this study, but he serves on the advisory boards of several pharmaceutical companies.

The study followed AK lesions for 11 months in 26 individuals with extensive actinic damage.

At baseline, the subjects had 10–40 actinic lesions and at least one prior histological diagnosis of an AK or a nonmelanoma skin cancer.

The subjects' AKs were mapped at baseline and again at 3, 6, 9, and 11 months.

The lesions also were biopsied at baseline and the end of the study. "If a lesion that had been selected for biopsy was no longer present clinically, the site where it had been was still biopsied," Dr. Elmets explained.

At baseline, there were a total of 610 AKs in the study group (mean 23.5 per individual). At the end of the study, this number was not significantly different despite the development of 973 new lesions over the 11-month period.

About 40% of the lesions present at baseline had regressed by month 11, and nearly 200 of the lesions that were present at baseline regressed and then recurred, he said. "A total of 51 of the lesions regressed twice."

Using a histologic grading scheme that was based on a cervical dysplasia model, Dr. Elmets noted little progression in the severity of lesions in terms of proliferation, atypia, or both features. "The histologic appearance seems to accurately correlate with the clinical appearance, and over the course of 11 months there was little evidence of histologic progression."

AKs have been thought to be precursors to squamous cell carcinomas in some cases.

The presence of AKs is strongly predictive of individuals who are at increased risk for basal cell and squamous cell carcinomas, noted Dr. Elmets.

The pattern of regression and recurrence of actinic keratoses may have implications for the treatment of the lesions. Courtesy Dr. Roger I. Ceilley

MONTREAL — Actinic keratoses are dynamic lesions and their expression varies over time, based on the results of an 11-month study of the natural course of the lesions in people with extensive actinic damage.

"At any one time, less than half of the lesions are evident clinically," said Dr. Craig Elmets, who reported his findings at the annual meeting of the Society for Investigative Dermatology.

The pattern of regression and recurrence of actinic keratoses (AK) has implications for the treatment of the lesions, said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

"If one is going to treat individual lesions, then they need to be treated aggressively because at any one time only a minority of the [visible] AKs are present," he said. "In patients with extensive actinic damage, peel treatment may be a very good approach to treating these lesions."

Dr. Elmets did not disclose any conflicts of interest in regard to this study, but he serves on the advisory boards of several pharmaceutical companies.

The study followed AK lesions for 11 months in 26 individuals with extensive actinic damage.

At baseline, the subjects had 10–40 actinic lesions and at least one prior histological diagnosis of an AK or a nonmelanoma skin cancer.

The subjects' AKs were mapped at baseline and again at 3, 6, 9, and 11 months.

The lesions also were biopsied at baseline and the end of the study. "If a lesion that had been selected for biopsy was no longer present clinically, the site where it had been was still biopsied," Dr. Elmets explained.

At baseline, there were a total of 610 AKs in the study group (mean 23.5 per individual). At the end of the study, this number was not significantly different despite the development of 973 new lesions over the 11-month period.

About 40% of the lesions present at baseline had regressed by month 11, and nearly 200 of the lesions that were present at baseline regressed and then recurred, he said. "A total of 51 of the lesions regressed twice."

Using a histologic grading scheme that was based on a cervical dysplasia model, Dr. Elmets noted little progression in the severity of lesions in terms of proliferation, atypia, or both features. "The histologic appearance seems to accurately correlate with the clinical appearance, and over the course of 11 months there was little evidence of histologic progression."

AKs have been thought to be precursors to squamous cell carcinomas in some cases.

The presence of AKs is strongly predictive of individuals who are at increased risk for basal cell and squamous cell carcinomas, noted Dr. Elmets.

The pattern of regression and recurrence of actinic keratoses may have implications for the treatment of the lesions. Courtesy Dr. Roger I. Ceilley

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR

MONTREAL — Mortality rates are significantly increased in patients with severe psoriasis compared with the general population, according to two new studies.

But studies have conflicting results regarding the cause of death, researchers reported at the annual meeting of the Society for Investigative Dermatology. A study by Dr. Rahat Azfar showed an age-dependent, significantly increased risk of cardiovascular death with severe psoriasis, compared with patients without psoriasis.

“Severe psoriasis may be an independent risk factor for cardiovascular mortality,” noted Dr. Azfar of the University of Pennsylvania, Philadelphia, whose study showed a 50% increase in cardiovascular death.

Her findings are in direct contrast to another study presented in the same session and conflict with a growing body of evidence. Dr. Robert Stern presented results from the 30-year PUVA Follow-Up Study, which showed no increase in cardiovascular death risk in severe psoriasis patients, all of whom had undergone PUVA.

“In patients with extremely severe psoriasis, there is an increased risk of death from noncardiovascular, but not cardiovascular causes,” said Dr. Stern, professor of dermatology at Harvard Medical School and vice chair of dermatology at Beth Israel Deaconess Medical Center in Boston.

“Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done,” commented Dr. Azfar, who declared no conflicts of interest.

Her study, which she presented at the meeting, was funded by the National Institutes of Health and a grant from Centocor. It examined more than 3,000 patients with severe psoriasis, matched to more than 14,000 controls from the United Kingdom's General Practice Research Database.

Compared with controls, patients with severe psoriasis had a significantly increased risk of all-cause mortality (odds ratio 1.78), she said. After the researchers controlled for traditional cardiovascular risk factors, psoriasis patients had a clinically significant increased risk of cardiovascular death (hazard ratio [HR] 1.55). This risk was modified by age, with patients aged 40 and younger being at greater risk (HR 2.65) than patients aged between 41 and 60 (HR 1.90). This translated to an excess risk of 5.78 cardiovascular deaths per 10,000 person-years at age 40, and 58.9 per 10,000 person-years at age 60, she said.

Dr. Stern, who declared no conflicts of interest, agreed that cardiovascular risk factors are important, but his data suggest they are no more important than other risk factors.

The data show “that liver disease and nonmelanoma skin cancer accounted for more than half the approximately 70 excess deaths we observed,” he said. His prospective study followed 1,376 patients from the PUVA Follow-Up for 28 years, from 1976 to 2004. The patients had participated in a therapeutic PUVA study in 1975–1976 in 16 tertiary care academic centers across the United States.

Comparing the observed and expected mortality rates among patients and controls, the researchers found an increased all-cause mortality rate (HR 1.51) among only those patients with the most severe psoriasis. When cause of death was examined in this group, noncardiovascular reasons explained the increased risk (HR 1.74), and there was a nonsignificant increase in the rate of cardiovascular deaths, compared with controls (HR 1.29), Dr. Stern said.

“Dr. Stern's study results need to be interpreted with extreme caution due to the inherent bias in his study design,” warned Dr. Joel Gelfand, also of the University of Pennsylvania, and principal investigator on Dr. Azfar's study.

Dr. Stern's study design compares apples to oranges, commented Dr. Gelfand. “Patients who participate in psoriasis clinical trials at tertiary care medical centers may be healthier, better educated, and have better access to medical care than the general U.S. population,” he noted. “Our study … was population based.”

'Previous studies of cardiovascular mortality have not controlled for traditional CV risk factors, as our work has done.' DR. AZFAR

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 [cyclo-oxygenase-2] is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” reported Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

“There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10–40 actinic keratoses (AK), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, as well as between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, said Dr. Elmets. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared to placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction, compared to placebo-treated controls,” he said.

Looking at the two types of lesions separately, treatment with celecoxib resulted in a 58% reduction in squamous cell carcinomas (SCC), and a 62% reduction in basal cell carcinomas (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study.

“We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than” placebo patients.

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

Of the 238 patients enrolled, 36 withdrew from the treatment group and 24 withdrew from the placebo group. The major reasons for withdrawal were disease progression, withdrawal of consent, the use of an excluded medication, an adverse event, and loss to follow up.

“The data is very compelling,” said Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2–5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results.

A study that she has just completed found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. And a previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100[13]:967–71).

In addition, she said celecoxib's lack of effect on AKs is a puzzling result. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 [cyclo-oxygenase-2] is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” reported Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

“There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10–40 actinic keratoses (AK), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, as well as between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, said Dr. Elmets. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared to placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction, compared to placebo-treated controls,” he said.

Looking at the two types of lesions separately, treatment with celecoxib resulted in a 58% reduction in squamous cell carcinomas (SCC), and a 62% reduction in basal cell carcinomas (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study.

“We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than” placebo patients.

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

Of the 238 patients enrolled, 36 withdrew from the treatment group and 24 withdrew from the placebo group. The major reasons for withdrawal were disease progression, withdrawal of consent, the use of an excluded medication, an adverse event, and loss to follow up.

“The data is very compelling,” said Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2–5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results.

A study that she has just completed found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. And a previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100[13]:967–71).

In addition, she said celecoxib's lack of effect on AKs is a puzzling result. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 [cyclo-oxygenase-2] is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” reported Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham.

“There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10–40 actinic keratoses (AK), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, as well as between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, said Dr. Elmets. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared to placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction, compared to placebo-treated controls,” he said.

Looking at the two types of lesions separately, treatment with celecoxib resulted in a 58% reduction in squamous cell carcinomas (SCC), and a 62% reduction in basal cell carcinomas (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study.

“We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than” placebo patients.

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

Of the 238 patients enrolled, 36 withdrew from the treatment group and 24 withdrew from the placebo group. The major reasons for withdrawal were disease progression, withdrawal of consent, the use of an excluded medication, an adverse event, and loss to follow up.

“The data is very compelling,” said Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2–5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results.

A study that she has just completed found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. And a previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100[13]:967–71).

In addition, she said celecoxib's lack of effect on AKs is a puzzling result. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

MONTREAL — A genetic signature involving 18 genes can reliably predict response to pegylated interferon α plus ribavirin therapy in patients infected with hepatitis C, reported Dr. Limin Chen at Canadian Digestive Diseases Week.

This finding “could form the basis for a diagnostic tool to encourage treatment compliance,” Dr. Chen said in an interview. The results also confirm the findings of in vitro studies by Dr. Chen's group from the University of Toronto.

His group previously identified gene expression differences in the pretreatment liver biopsies of hepatitis C virus (HCV) patients who subsequently responded and those who failed to respond to pegylated interferon α plus ribavirin, showing that these two groups “differ fundamentally in their innate [interferon] response to HCV infection” (Gastroenterology 2005;128:1437-44).

Upregulation of an 18-gene signature known as USP18 predicted lack of response to treatment, and another study by the same group showed that silencing this gene signature in vitro could improve treatment response.

“We were able to show that if we silence this USP18 gene, the virus actually gets more sensitive to interferon. In other words, we can use much less interferon to kill the virus,” Dr. Chen said.

The group's latest work validates the findings from a prospective cohort study of 78 HCV patients (mean age, 51 years): 23 nonresponders and 55 responders. Using pretreatment liver biopsies, “we confirmed that USP18 is more highly expressed in nonresponders,” he said.

The study showed that the genetic evaluation of pretreatment liver biopsies with regard to this gene signature can predict treatment response with a positive predictive value of 96%. However, the sensitivity was only 50%. “Therefore, you cannot use it to exclude patients from treatment,” he said.

Current combination treatment with pegylated interferon α plus ribavirin has only a 50% success rate, and patient compliance is jeopardized by the significant side effects and expense, Dr. Chen explained. Genetic markers such as USP18 that predict good treatment response might help physicians encourage compliance in certain patients, he said at the meeting, sponsored by the Canadian Association of Gastroenterology.

MONTREAL — A genetic signature involving 18 genes can reliably predict response to pegylated interferon α plus ribavirin therapy in patients infected with hepatitis C, reported Dr. Limin Chen at Canadian Digestive Diseases Week.

This finding “could form the basis for a diagnostic tool to encourage treatment compliance,” Dr. Chen said in an interview. The results also confirm the findings of in vitro studies by Dr. Chen's group from the University of Toronto.

His group previously identified gene expression differences in the pretreatment liver biopsies of hepatitis C virus (HCV) patients who subsequently responded and those who failed to respond to pegylated interferon α plus ribavirin, showing that these two groups “differ fundamentally in their innate [interferon] response to HCV infection” (Gastroenterology 2005;128:1437-44).

Upregulation of an 18-gene signature known as USP18 predicted lack of response to treatment, and another study by the same group showed that silencing this gene signature in vitro could improve treatment response.

“We were able to show that if we silence this USP18 gene, the virus actually gets more sensitive to interferon. In other words, we can use much less interferon to kill the virus,” Dr. Chen said.

The group's latest work validates the findings from a prospective cohort study of 78 HCV patients (mean age, 51 years): 23 nonresponders and 55 responders. Using pretreatment liver biopsies, “we confirmed that USP18 is more highly expressed in nonresponders,” he said.

The study showed that the genetic evaluation of pretreatment liver biopsies with regard to this gene signature can predict treatment response with a positive predictive value of 96%. However, the sensitivity was only 50%. “Therefore, you cannot use it to exclude patients from treatment,” he said.

Current combination treatment with pegylated interferon α plus ribavirin has only a 50% success rate, and patient compliance is jeopardized by the significant side effects and expense, Dr. Chen explained. Genetic markers such as USP18 that predict good treatment response might help physicians encourage compliance in certain patients, he said at the meeting, sponsored by the Canadian Association of Gastroenterology.

MONTREAL — A genetic signature involving 18 genes can reliably predict response to pegylated interferon α plus ribavirin therapy in patients infected with hepatitis C, reported Dr. Limin Chen at Canadian Digestive Diseases Week.

This finding “could form the basis for a diagnostic tool to encourage treatment compliance,” Dr. Chen said in an interview. The results also confirm the findings of in vitro studies by Dr. Chen's group from the University of Toronto.

His group previously identified gene expression differences in the pretreatment liver biopsies of hepatitis C virus (HCV) patients who subsequently responded and those who failed to respond to pegylated interferon α plus ribavirin, showing that these two groups “differ fundamentally in their innate [interferon] response to HCV infection” (Gastroenterology 2005;128:1437-44).

Upregulation of an 18-gene signature known as USP18 predicted lack of response to treatment, and another study by the same group showed that silencing this gene signature in vitro could improve treatment response.

“We were able to show that if we silence this USP18 gene, the virus actually gets more sensitive to interferon. In other words, we can use much less interferon to kill the virus,” Dr. Chen said.

The group's latest work validates the findings from a prospective cohort study of 78 HCV patients (mean age, 51 years): 23 nonresponders and 55 responders. Using pretreatment liver biopsies, “we confirmed that USP18 is more highly expressed in nonresponders,” he said.

The study showed that the genetic evaluation of pretreatment liver biopsies with regard to this gene signature can predict treatment response with a positive predictive value of 96%. However, the sensitivity was only 50%. “Therefore, you cannot use it to exclude patients from treatment,” he said.

Current combination treatment with pegylated interferon α plus ribavirin has only a 50% success rate, and patient compliance is jeopardized by the significant side effects and expense, Dr. Chen explained. Genetic markers such as USP18 that predict good treatment response might help physicians encourage compliance in certain patients, he said at the meeting, sponsored by the Canadian Association of Gastroenterology.

MONTREAL — When rating the impact of ulcerative colitis, patients and physicians are not always on the same page, according to a study presented in two posters at the Canadian Digestive Diseases Week.

Adult patients with ulcerative colitis (UC) report a heavier psychological burden than do adult patients with rheumatoid arthritis (RA), migraine, or asthma, but gastroenterologists often underestimate the impact of this disease, reported Dr. David T. Rubin of the University of Chicago Medical Center, and his colleagues.

The UC: New Observations on Remission Management and Lifestyle (NORMAL) study, sponsored by Shire Pharmaceuticals, included 451 adult UC patients and 300 gastroenterologists. The participants completed an online survey in February and March 2007. The survey also included 309 RA patients, 305 migraine patients, and 305 asthma patients, all of whom were adults.

The UC patients were not necessarily being treated by the physicians in the study, as both groups were recruited separately.

Based on discussions with their physicians, 20% of the UC patients reported mild disease, 63% reported moderate disease, and 13% reported severe disease. Gastroenterologists tended to underestimate the frequency of disease flares in these patient groups, with 58% estimating only one flare per year in the mild UC group (patients self-reported a mean of five).

For the moderate UC group, 70% of the physicians estimated two or three flares, whereas patients self-reported a mean of eight. For the severe UC group, 22% of the physicians estimated 6 or more flares, whereas patients self-reported a mean of 11.

Furthermore, gastroenterologists underestimated how many patients thought that feeling unwell was a part of normal life, predicting this would be true for 37% of patients, when actually 73% of patients reported this, the authors wrote.

Compared with patients who had other illnesses, a significantly higher proportion (53%) of UC patients felt that their disease was controlling their lives, compared with RA patients (44%), migraine patients (37%), or asthma patients (19%). Stress, depression, and embarrassment were reported by 82%, 62%, and 70% of UC patients, respectively, compared with significantly lower proportions among all the other patients.

Physicians and patients had more similar views regarding the challenges of treatment with 5-aminosalicylic acid (5-ASA) medications. Whereas 41% of physicians believed patients were not adherent, 46% of patients reported that they had missed taking some of their medication in the previous week. Almost all (90%) of the gastroenterologists and 42% of the patients reported that it was difficult to take the medication at the prescribed intervals. Most patients (89%) reported that they would be interested in trying a once-daily 5-ASA medication.

“Patients with UC may benefit from improved disease management strategies (including simplified therapeutic regimens), disease education, and enhanced communication with gastroenterologists,” the authors concluded.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — When rating the impact of ulcerative colitis, patients and physicians are not always on the same page, according to a study presented in two posters at the Canadian Digestive Diseases Week.

Adult patients with ulcerative colitis (UC) report a heavier psychological burden than do adult patients with rheumatoid arthritis (RA), migraine, or asthma, but gastroenterologists often underestimate the impact of this disease, reported Dr. David T. Rubin of the University of Chicago Medical Center, and his colleagues.

The UC: New Observations on Remission Management and Lifestyle (NORMAL) study, sponsored by Shire Pharmaceuticals, included 451 adult UC patients and 300 gastroenterologists. The participants completed an online survey in February and March 2007. The survey also included 309 RA patients, 305 migraine patients, and 305 asthma patients, all of whom were adults.

The UC patients were not necessarily being treated by the physicians in the study, as both groups were recruited separately.

Based on discussions with their physicians, 20% of the UC patients reported mild disease, 63% reported moderate disease, and 13% reported severe disease. Gastroenterologists tended to underestimate the frequency of disease flares in these patient groups, with 58% estimating only one flare per year in the mild UC group (patients self-reported a mean of five).

For the moderate UC group, 70% of the physicians estimated two or three flares, whereas patients self-reported a mean of eight. For the severe UC group, 22% of the physicians estimated 6 or more flares, whereas patients self-reported a mean of 11.

Furthermore, gastroenterologists underestimated how many patients thought that feeling unwell was a part of normal life, predicting this would be true for 37% of patients, when actually 73% of patients reported this, the authors wrote.

Compared with patients who had other illnesses, a significantly higher proportion (53%) of UC patients felt that their disease was controlling their lives, compared with RA patients (44%), migraine patients (37%), or asthma patients (19%). Stress, depression, and embarrassment were reported by 82%, 62%, and 70% of UC patients, respectively, compared with significantly lower proportions among all the other patients.

Physicians and patients had more similar views regarding the challenges of treatment with 5-aminosalicylic acid (5-ASA) medications. Whereas 41% of physicians believed patients were not adherent, 46% of patients reported that they had missed taking some of their medication in the previous week. Almost all (90%) of the gastroenterologists and 42% of the patients reported that it was difficult to take the medication at the prescribed intervals. Most patients (89%) reported that they would be interested in trying a once-daily 5-ASA medication.

“Patients with UC may benefit from improved disease management strategies (including simplified therapeutic regimens), disease education, and enhanced communication with gastroenterologists,” the authors concluded.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — When rating the impact of ulcerative colitis, patients and physicians are not always on the same page, according to a study presented in two posters at the Canadian Digestive Diseases Week.

Adult patients with ulcerative colitis (UC) report a heavier psychological burden than do adult patients with rheumatoid arthritis (RA), migraine, or asthma, but gastroenterologists often underestimate the impact of this disease, reported Dr. David T. Rubin of the University of Chicago Medical Center, and his colleagues.

The UC: New Observations on Remission Management and Lifestyle (NORMAL) study, sponsored by Shire Pharmaceuticals, included 451 adult UC patients and 300 gastroenterologists. The participants completed an online survey in February and March 2007. The survey also included 309 RA patients, 305 migraine patients, and 305 asthma patients, all of whom were adults.

The UC patients were not necessarily being treated by the physicians in the study, as both groups were recruited separately.

Based on discussions with their physicians, 20% of the UC patients reported mild disease, 63% reported moderate disease, and 13% reported severe disease. Gastroenterologists tended to underestimate the frequency of disease flares in these patient groups, with 58% estimating only one flare per year in the mild UC group (patients self-reported a mean of five).

For the moderate UC group, 70% of the physicians estimated two or three flares, whereas patients self-reported a mean of eight. For the severe UC group, 22% of the physicians estimated 6 or more flares, whereas patients self-reported a mean of 11.

Furthermore, gastroenterologists underestimated how many patients thought that feeling unwell was a part of normal life, predicting this would be true for 37% of patients, when actually 73% of patients reported this, the authors wrote.

Compared with patients who had other illnesses, a significantly higher proportion (53%) of UC patients felt that their disease was controlling their lives, compared with RA patients (44%), migraine patients (37%), or asthma patients (19%). Stress, depression, and embarrassment were reported by 82%, 62%, and 70% of UC patients, respectively, compared with significantly lower proportions among all the other patients.

Physicians and patients had more similar views regarding the challenges of treatment with 5-aminosalicylic acid (5-ASA) medications. Whereas 41% of physicians believed patients were not adherent, 46% of patients reported that they had missed taking some of their medication in the previous week. Almost all (90%) of the gastroenterologists and 42% of the patients reported that it was difficult to take the medication at the prescribed intervals. Most patients (89%) reported that they would be interested in trying a once-daily 5-ASA medication.

“Patients with UC may benefit from improved disease management strategies (including simplified therapeutic regimens), disease education, and enhanced communication with gastroenterologists,” the authors concluded.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — Several noninvasive tests used in combination may be a more sensitive method for monitoring celiac disease activity and patient compliance with the gluten-free diet than are current approaches.

At Canadian Digestive Diseases Week, Dr. Alaa Rostom said that the majority of his celiac disease patients make every effort to avoid gluten, but hidden sources of this protein—found in wheat, rye, and barley—are often responsible for persistent symptoms. Dr. Rostom, from the University of Calgary (Alta.), presented his research in a poster at the meeting.

“The gold standard for diagnosis is positive serology and a consistent biopsy. But once a gluten-free diet is started, it takes large dietary indiscretions to turn the serology positive again,” he said.

Dr. Rostom polled a celiac disease expert panel regarding the accuracy of various noninvasive tests for monitoring disease activity and dietary adherence. The experts were asked to rank their top six tests, and tests were included in a final list if they were ranked by more than 50% of panel members. Univariate analysis revealed that the use of serology, the lactulose/mannitol test for intestinal permeability, body mass index, triceps skinfold thickness, the gastrointestinal symptom rating score (GSRS), and a quality of life measure were all considered useful by panel members.

Dr. Rostom then calculated the sensitivity and specificity of the various tests based on a retrospective data set of about 200 patients. “Serology has important sensitivity, about 90%, but the specificity is less than 90%, which explains why it won't detect small amounts of gluten exposure,” he said. “On the other hand, the lactulose/mannitol test isn't very sensitive but it has a pretty high specificity.” Therefore, combining results from both of these tests proved more useful than relying on either one alone, and yielded both a sensitivity of 92% and a specificity of 92%, which is comparable to results obtained from intestinal biopsy, he explained.

By using these results, Dr. Rostom compiled the Celiac Disease Activity Scoring System (CeDARS), which is now being validated in two randomized controlled trials. “I think probably the best assessment will likely come from combining serology, plus the lactulose/mannitol test, plus GSRS,” he suggested, pointing out that the beauty of this particular combination of tests is that it can capture different stages of response to gluten exposure.

Dr. Rostom emphasized that the goal of CeDARS is not to replace, but rather to enhance annual serology, which is currently recommended for monitoring celiac disease patients.

MONTREAL — Several noninvasive tests used in combination may be a more sensitive method for monitoring celiac disease activity and patient compliance with the gluten-free diet than are current approaches.

At Canadian Digestive Diseases Week, Dr. Alaa Rostom said that the majority of his celiac disease patients make every effort to avoid gluten, but hidden sources of this protein—found in wheat, rye, and barley—are often responsible for persistent symptoms. Dr. Rostom, from the University of Calgary (Alta.), presented his research in a poster at the meeting.

“The gold standard for diagnosis is positive serology and a consistent biopsy. But once a gluten-free diet is started, it takes large dietary indiscretions to turn the serology positive again,” he said.

Dr. Rostom polled a celiac disease expert panel regarding the accuracy of various noninvasive tests for monitoring disease activity and dietary adherence. The experts were asked to rank their top six tests, and tests were included in a final list if they were ranked by more than 50% of panel members. Univariate analysis revealed that the use of serology, the lactulose/mannitol test for intestinal permeability, body mass index, triceps skinfold thickness, the gastrointestinal symptom rating score (GSRS), and a quality of life measure were all considered useful by panel members.

Dr. Rostom then calculated the sensitivity and specificity of the various tests based on a retrospective data set of about 200 patients. “Serology has important sensitivity, about 90%, but the specificity is less than 90%, which explains why it won't detect small amounts of gluten exposure,” he said. “On the other hand, the lactulose/mannitol test isn't very sensitive but it has a pretty high specificity.” Therefore, combining results from both of these tests proved more useful than relying on either one alone, and yielded both a sensitivity of 92% and a specificity of 92%, which is comparable to results obtained from intestinal biopsy, he explained.

By using these results, Dr. Rostom compiled the Celiac Disease Activity Scoring System (CeDARS), which is now being validated in two randomized controlled trials. “I think probably the best assessment will likely come from combining serology, plus the lactulose/mannitol test, plus GSRS,” he suggested, pointing out that the beauty of this particular combination of tests is that it can capture different stages of response to gluten exposure.

Dr. Rostom emphasized that the goal of CeDARS is not to replace, but rather to enhance annual serology, which is currently recommended for monitoring celiac disease patients.

MONTREAL — Several noninvasive tests used in combination may be a more sensitive method for monitoring celiac disease activity and patient compliance with the gluten-free diet than are current approaches.

At Canadian Digestive Diseases Week, Dr. Alaa Rostom said that the majority of his celiac disease patients make every effort to avoid gluten, but hidden sources of this protein—found in wheat, rye, and barley—are often responsible for persistent symptoms. Dr. Rostom, from the University of Calgary (Alta.), presented his research in a poster at the meeting.

“The gold standard for diagnosis is positive serology and a consistent biopsy. But once a gluten-free diet is started, it takes large dietary indiscretions to turn the serology positive again,” he said.

Dr. Rostom polled a celiac disease expert panel regarding the accuracy of various noninvasive tests for monitoring disease activity and dietary adherence. The experts were asked to rank their top six tests, and tests were included in a final list if they were ranked by more than 50% of panel members. Univariate analysis revealed that the use of serology, the lactulose/mannitol test for intestinal permeability, body mass index, triceps skinfold thickness, the gastrointestinal symptom rating score (GSRS), and a quality of life measure were all considered useful by panel members.

Dr. Rostom then calculated the sensitivity and specificity of the various tests based on a retrospective data set of about 200 patients. “Serology has important sensitivity, about 90%, but the specificity is less than 90%, which explains why it won't detect small amounts of gluten exposure,” he said. “On the other hand, the lactulose/mannitol test isn't very sensitive but it has a pretty high specificity.” Therefore, combining results from both of these tests proved more useful than relying on either one alone, and yielded both a sensitivity of 92% and a specificity of 92%, which is comparable to results obtained from intestinal biopsy, he explained.

By using these results, Dr. Rostom compiled the Celiac Disease Activity Scoring System (CeDARS), which is now being validated in two randomized controlled trials. “I think probably the best assessment will likely come from combining serology, plus the lactulose/mannitol test, plus GSRS,” he suggested, pointing out that the beauty of this particular combination of tests is that it can capture different stages of response to gluten exposure.

Dr. Rostom emphasized that the goal of CeDARS is not to replace, but rather to enhance annual serology, which is currently recommended for monitoring celiac disease patients.

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were 2 cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” said Dr. Williams at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16 to 78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male, 74% presented with dysphagia, and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, said Dr. Williams. In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Overall, this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” he said, recommending medical treatment with fluticasone as the first-line therapy.

An endoscopic image shows the typical appearance of eosinophilic esophagitis. Courtesy Dr. Chad Williams

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were 2 cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” said Dr. Williams at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16 to 78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male, 74% presented with dysphagia, and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, said Dr. Williams. In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Overall, this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” he said, recommending medical treatment with fluticasone as the first-line therapy.

An endoscopic image shows the typical appearance of eosinophilic esophagitis. Courtesy Dr. Chad Williams

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were 2 cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” said Dr. Williams at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16 to 78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male, 74% presented with dysphagia, and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, said Dr. Williams. In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Overall, this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” he said, recommending medical treatment with fluticasone as the first-line therapy.

An endoscopic image shows the typical appearance of eosinophilic esophagitis. Courtesy Dr. Chad Williams

Emergency on-call coverage from specialist physicians, including dermatologists, is "unraveling" at hospitals across the country, resulting in delayed treatment, patient transfers, permanent injuries, and even death, according to a study from the Center for Studying Health System Change, a nonpartisan policy research group in Washington.

While the problem is predominantly an issue for hospital emergency departments, it also is becoming increasingly problematic for inpatients who need urgent specialty care, according to the report. The findings are based on 2007 data from 12 nationally representative communities: Boston; Cleveland; Greenville, S.C.; Indianapolis; Lansing, Mich.; Little Rock, Ark.; Miami; Northern New Jersey; Orange County, Calif; Phoenix; Seattle; and Syracuse, N.Y.

The picture is particularly grim given the fact that overall ED utilization rates have risen by 7% in the past decade, from 36.9 to 39.6 visits per 100 people, according to the report. While insured people account for the vast majority of ED visits, "the proportion of visits by uninsured people is rising at a relatively higher rate," the study's authors wrote.

Citing a 2006 paper from the American College of Emergency Physicians, the study reported that 73% of emergency departments in the United States report inadequate on-call coverage by specialist physicians. In particularly short supply are plastic surgeons, ophthalmologists, dermatologists, orthopedic surgeons, neurosurgeons, trauma surgeons, hand surgeons, obstetrician-gynecologists, and neurologists, While an actual shortage of such physicians may sometimes be to blame, "physician unwillingness to take call appears to be a more pressing issue for many hospitals," the study authors stated.

Although unwillingness to accept on-call duty is largely influenced by quality of life issues, the requirement to provide on-call coverage has traditionally been mandated by hospitals under the Emergency Medical Treatment and Labor Act. However, many specialists are now shifting their practices away from the hospital setting, and are no longer obligated by medical staff privileges, noted the report's authors.

Many physicians also believe payment for on-call care is inadequate, especially when they are caring for uninsured patients. Specialists are also concerned that providing emergency care may increase their exposure to medical liability and drive up the cost of their malpractice premiums, according to the report.

As a result, adverse patient outcomes are reported. One study found that 21% of patient deaths or permanent injuries related to ED treatment delays are attributed to lack of specialists' availability, noted the report. Complete lack of access to specialty care in some EDs is forcing either travel or transfer of patients. And for the physicians who continue to provide on-call coverage, increasing workload and decreasing morale may put patients further at risk.

Crisis May Drive Docs Away

"It's not a surprise that we're having this problem—it's a surprise to me that we have any on-call specialists at all," Dr. Todd Taylor, previously an emergency physician and speaker for the ACEP Council, said in an interview. Dr. Taylor left clinical medicine last summer to work in the computer industry, he said, because the risks of liability were more than he could justify.

For Dr. Taylor, it is these very liability risks that are at the root of the current on-call crisis. "The liability issue has become the overriding barrier to physicians being willing to put themselves at risk," he said. "Until and unless you solve the liability crisis in emergency care and health care in general, nothing else you do matters."

Most on-call specialists have a private practice outside of the emergency department—they don't need the ED—so it's not a big surprise they were the first to leave, he explained. "But now that core emergency physicians, who were trained to practice only emergency medicine, are making the same choices, that should be a wake-up call," Dr. Taylor said. "That's what's different now compared to 2 or 3 years ago."

On-Call Shortage Cripples Trauma Care

Lack of optimal on-call coverage is what will ultimately "cripple" trauma and emergency care, agreed Dr. L. D. Britt, professor of surgery at the Eastern Virginia Medical School in Norfolk. "Some of the specialists are asking for unbelievably exorbitant fees to provide coverage, and hospitals are being held hostage," he said in an interview.

While Dr. Britt sympathizes with physicians' struggles with payment and liability issues, he believes the true bottom line is simply that obligations are being overlooked. "It cannot be everyone saying, 'I can't do this.' Something has to give," Dr. Britt said. "Speaking for myself, I consider it my obligation to provide emergency coverage if I am on call. I know that's my responsibility—and I'm a chairman of a department. Some people can find ways out of it, but I'm saying we cannot have all those options out there."

In addition, high fees charged by specialists and paid by hospitals for on-call coverage are not justified based on the premise that on-call coverage increases a physician's liability exposure, he said. "Being on call doesn't give you more litigation than being in general surgery—that's well documented," he said.

Dr. Taylor disagreed. "The literature is very clear that emergency care is one of the highest liability environments in health care," he said. "You only have to look at what's happened to emergency physician malpractice premiums relative to others not involved in emergency care. Mine almost doubled the last 3 years I worked."

Emergency on-call coverage from specialist physicians, including dermatologists, is "unraveling" at hospitals across the country, resulting in delayed treatment, patient transfers, permanent injuries, and even death, according to a study from the Center for Studying Health System Change, a nonpartisan policy research group in Washington.

While the problem is predominantly an issue for hospital emergency departments, it also is becoming increasingly problematic for inpatients who need urgent specialty care, according to the report. The findings are based on 2007 data from 12 nationally representative communities: Boston; Cleveland; Greenville, S.C.; Indianapolis; Lansing, Mich.; Little Rock, Ark.; Miami; Northern New Jersey; Orange County, Calif; Phoenix; Seattle; and Syracuse, N.Y.

The picture is particularly grim given the fact that overall ED utilization rates have risen by 7% in the past decade, from 36.9 to 39.6 visits per 100 people, according to the report. While insured people account for the vast majority of ED visits, "the proportion of visits by uninsured people is rising at a relatively higher rate," the study's authors wrote.

Citing a 2006 paper from the American College of Emergency Physicians, the study reported that 73% of emergency departments in the United States report inadequate on-call coverage by specialist physicians. In particularly short supply are plastic surgeons, ophthalmologists, dermatologists, orthopedic surgeons, neurosurgeons, trauma surgeons, hand surgeons, obstetrician-gynecologists, and neurologists, While an actual shortage of such physicians may sometimes be to blame, "physician unwillingness to take call appears to be a more pressing issue for many hospitals," the study authors stated.

Although unwillingness to accept on-call duty is largely influenced by quality of life issues, the requirement to provide on-call coverage has traditionally been mandated by hospitals under the Emergency Medical Treatment and Labor Act. However, many specialists are now shifting their practices away from the hospital setting, and are no longer obligated by medical staff privileges, noted the report's authors.

Many physicians also believe payment for on-call care is inadequate, especially when they are caring for uninsured patients. Specialists are also concerned that providing emergency care may increase their exposure to medical liability and drive up the cost of their malpractice premiums, according to the report.

As a result, adverse patient outcomes are reported. One study found that 21% of patient deaths or permanent injuries related to ED treatment delays are attributed to lack of specialists' availability, noted the report. Complete lack of access to specialty care in some EDs is forcing either travel or transfer of patients. And for the physicians who continue to provide on-call coverage, increasing workload and decreasing morale may put patients further at risk.

Crisis May Drive Docs Away

"It's not a surprise that we're having this problem—it's a surprise to me that we have any on-call specialists at all," Dr. Todd Taylor, previously an emergency physician and speaker for the ACEP Council, said in an interview. Dr. Taylor left clinical medicine last summer to work in the computer industry, he said, because the risks of liability were more than he could justify.

For Dr. Taylor, it is these very liability risks that are at the root of the current on-call crisis. "The liability issue has become the overriding barrier to physicians being willing to put themselves at risk," he said. "Until and unless you solve the liability crisis in emergency care and health care in general, nothing else you do matters."

Most on-call specialists have a private practice outside of the emergency department—they don't need the ED—so it's not a big surprise they were the first to leave, he explained. "But now that core emergency physicians, who were trained to practice only emergency medicine, are making the same choices, that should be a wake-up call," Dr. Taylor said. "That's what's different now compared to 2 or 3 years ago."

On-Call Shortage Cripples Trauma Care

Lack of optimal on-call coverage is what will ultimately "cripple" trauma and emergency care, agreed Dr. L. D. Britt, professor of surgery at the Eastern Virginia Medical School in Norfolk. "Some of the specialists are asking for unbelievably exorbitant fees to provide coverage, and hospitals are being held hostage," he said in an interview.

While Dr. Britt sympathizes with physicians' struggles with payment and liability issues, he believes the true bottom line is simply that obligations are being overlooked. "It cannot be everyone saying, 'I can't do this.' Something has to give," Dr. Britt said. "Speaking for myself, I consider it my obligation to provide emergency coverage if I am on call. I know that's my responsibility—and I'm a chairman of a department. Some people can find ways out of it, but I'm saying we cannot have all those options out there."

In addition, high fees charged by specialists and paid by hospitals for on-call coverage are not justified based on the premise that on-call coverage increases a physician's liability exposure, he said. "Being on call doesn't give you more litigation than being in general surgery—that's well documented," he said.

Dr. Taylor disagreed. "The literature is very clear that emergency care is one of the highest liability environments in health care," he said. "You only have to look at what's happened to emergency physician malpractice premiums relative to others not involved in emergency care. Mine almost doubled the last 3 years I worked."

Emergency on-call coverage from specialist physicians, including dermatologists, is "unraveling" at hospitals across the country, resulting in delayed treatment, patient transfers, permanent injuries, and even death, according to a study from the Center for Studying Health System Change, a nonpartisan policy research group in Washington.

While the problem is predominantly an issue for hospital emergency departments, it also is becoming increasingly problematic for inpatients who need urgent specialty care, according to the report. The findings are based on 2007 data from 12 nationally representative communities: Boston; Cleveland; Greenville, S.C.; Indianapolis; Lansing, Mich.; Little Rock, Ark.; Miami; Northern New Jersey; Orange County, Calif; Phoenix; Seattle; and Syracuse, N.Y.

The picture is particularly grim given the fact that overall ED utilization rates have risen by 7% in the past decade, from 36.9 to 39.6 visits per 100 people, according to the report. While insured people account for the vast majority of ED visits, "the proportion of visits by uninsured people is rising at a relatively higher rate," the study's authors wrote.

Citing a 2006 paper from the American College of Emergency Physicians, the study reported that 73% of emergency departments in the United States report inadequate on-call coverage by specialist physicians. In particularly short supply are plastic surgeons, ophthalmologists, dermatologists, orthopedic surgeons, neurosurgeons, trauma surgeons, hand surgeons, obstetrician-gynecologists, and neurologists, While an actual shortage of such physicians may sometimes be to blame, "physician unwillingness to take call appears to be a more pressing issue for many hospitals," the study authors stated.

Although unwillingness to accept on-call duty is largely influenced by quality of life issues, the requirement to provide on-call coverage has traditionally been mandated by hospitals under the Emergency Medical Treatment and Labor Act. However, many specialists are now shifting their practices away from the hospital setting, and are no longer obligated by medical staff privileges, noted the report's authors.

Many physicians also believe payment for on-call care is inadequate, especially when they are caring for uninsured patients. Specialists are also concerned that providing emergency care may increase their exposure to medical liability and drive up the cost of their malpractice premiums, according to the report.

As a result, adverse patient outcomes are reported. One study found that 21% of patient deaths or permanent injuries related to ED treatment delays are attributed to lack of specialists' availability, noted the report. Complete lack of access to specialty care in some EDs is forcing either travel or transfer of patients. And for the physicians who continue to provide on-call coverage, increasing workload and decreasing morale may put patients further at risk.

Crisis May Drive Docs Away

"It's not a surprise that we're having this problem—it's a surprise to me that we have any on-call specialists at all," Dr. Todd Taylor, previously an emergency physician and speaker for the ACEP Council, said in an interview. Dr. Taylor left clinical medicine last summer to work in the computer industry, he said, because the risks of liability were more than he could justify.

For Dr. Taylor, it is these very liability risks that are at the root of the current on-call crisis. "The liability issue has become the overriding barrier to physicians being willing to put themselves at risk," he said. "Until and unless you solve the liability crisis in emergency care and health care in general, nothing else you do matters."

Most on-call specialists have a private practice outside of the emergency department—they don't need the ED—so it's not a big surprise they were the first to leave, he explained. "But now that core emergency physicians, who were trained to practice only emergency medicine, are making the same choices, that should be a wake-up call," Dr. Taylor said. "That's what's different now compared to 2 or 3 years ago."

On-Call Shortage Cripples Trauma Care

Lack of optimal on-call coverage is what will ultimately "cripple" trauma and emergency care, agreed Dr. L. D. Britt, professor of surgery at the Eastern Virginia Medical School in Norfolk. "Some of the specialists are asking for unbelievably exorbitant fees to provide coverage, and hospitals are being held hostage," he said in an interview.

While Dr. Britt sympathizes with physicians' struggles with payment and liability issues, he believes the true bottom line is simply that obligations are being overlooked. "It cannot be everyone saying, 'I can't do this.' Something has to give," Dr. Britt said. "Speaking for myself, I consider it my obligation to provide emergency coverage if I am on call. I know that's my responsibility—and I'm a chairman of a department. Some people can find ways out of it, but I'm saying we cannot have all those options out there."

In addition, high fees charged by specialists and paid by hospitals for on-call coverage are not justified based on the premise that on-call coverage increases a physician's liability exposure, he said. "Being on call doesn't give you more litigation than being in general surgery—that's well documented," he said.

Dr. Taylor disagreed. "The literature is very clear that emergency care is one of the highest liability environments in health care," he said. "You only have to look at what's happened to emergency physician malpractice premiums relative to others not involved in emergency care. Mine almost doubled the last 3 years I worked."