Robert Finn

Many patients with Clostridium difficile infection experience repeated bouts of the illness, and a rule has been developed to accurately predict a patient's risk of recurrence, reported Dr. Mary Y. Hu and her colleagues.

The simple prediction rule takes into account a patient's age, use of antibiotics, and severity of disease. The researchers showed that the rule has a diagnostic accuracy of 72%.

These factors had been shown previously to be significant independent predictors of recurrent C. difficile diarrhea, wrote Dr. Hu of Harvard Medical School, Boston, and her colleagues. A fourth independent predictor—the serum level of antitoxin A IgG—appeared to reduce the accuracy of the rule (Gastroenterology 2009 April [doi:10.1053j.gastro.2008.12.038]).

The investigators derived the rule from a study of 63 patients hospitalized with C. difficile infection between January and May 1998, and validated it with data collected prospectively from 64 patients hospitalized between December 2004 and May 2006.

The rule assigns 1 point to each of the following three characteristics: age greater than 65 years, disease judged to be severe or fulminant in intensity, and additional antibiotic use after the discontinuation of therapy for C. difficile infection. In the validation group, recurrence occurred in 7 of 19 patients scoring 2 points or higher (37%) but in 6 of 45 patients scoring 0 or 1 (13%).

In the validation cohort, the sensitivity of the rule was 54%, the specificity was 77%, the positive predictive value was 37%, and the negative predictive value was 87%. The diagnostic accuracy was 72%. This compared favorably to the original derivation cohort, in which the rule's diagnostic accuracy was 77%.

They also tested a combined rule that assigned an additional 2 points to a serum antitoxin A IgG level less than 1.29 ELISA units. With a threshold of 4 points or above, this combined rule appeared promising among the derivation cohort: Of these patients, 16 had antitoxin A IgG data available. Of those, all eight patients in the high-risk group had recurrent C. difficile infection, while only one of the eight patients in the low-risk group had recurrence. In this analysis, the sensitivity of the rule was 89%, specificity was 100%, and diagnostic accuracy was 94%. This rule proved to be far less predictive in the validation cohort, in which 26 patients had antitoxin A IgG data available. Infection recurred in 3 of 6 patients in the high-risk group and 5 of 20 patients in the low-risk group. This translates to a sensitivity of 38%, specificity of 83%, and diagnostic accuracy of 69%.

The researchers advanced several hypotheses for the disappointing performance of the combined rule, including few serum samples available for antibody measurement and variations in the timing of antibody measurement. Also, the epidemiology of C. difficile infection changed between 1998 and 2004–2006.

The three-factor prediction rule for recurrence was “simple, reliable, and accurate,” according to the investigators. “This rule is valuable in clinical practice as it defines a high-risk population in whom awareness of the risk can facilitate more prompt recognition, diagnosis, and treatment of recurrent [C. difficile infection]. These patients are also most likely to benefit from interventions to prevent recurrence, such as infection control precautions [or] prudent use of antibiotics.”

The study was supported by grants from the National Institutes of Health and the Irish Health Research Board. Coauthor Dr. Ciar´n P. Kelly of Harvard Medical School acknowledged acting as a scientific consultant for and receiving research funding from several companies producing or developing treatments for C. difficile infection.

A simple new rule can be used to predict recurrence of C. difficile infection, which can cause repeated bouts of diarrhea. CDC/Dr. Gilda Jones

Many patients with Clostridium difficile infection experience repeated bouts of the illness, and a rule has been developed to accurately predict a patient's risk of recurrence, reported Dr. Mary Y. Hu and her colleagues.

The simple prediction rule takes into account a patient's age, use of antibiotics, and severity of disease. The researchers showed that the rule has a diagnostic accuracy of 72%.

These factors had been shown previously to be significant independent predictors of recurrent C. difficile diarrhea, wrote Dr. Hu of Harvard Medical School, Boston, and her colleagues. A fourth independent predictor—the serum level of antitoxin A IgG—appeared to reduce the accuracy of the rule (Gastroenterology 2009 April [doi:10.1053j.gastro.2008.12.038]).

The investigators derived the rule from a study of 63 patients hospitalized with C. difficile infection between January and May 1998, and validated it with data collected prospectively from 64 patients hospitalized between December 2004 and May 2006.

The rule assigns 1 point to each of the following three characteristics: age greater than 65 years, disease judged to be severe or fulminant in intensity, and additional antibiotic use after the discontinuation of therapy for C. difficile infection. In the validation group, recurrence occurred in 7 of 19 patients scoring 2 points or higher (37%) but in 6 of 45 patients scoring 0 or 1 (13%).

In the validation cohort, the sensitivity of the rule was 54%, the specificity was 77%, the positive predictive value was 37%, and the negative predictive value was 87%. The diagnostic accuracy was 72%. This compared favorably to the original derivation cohort, in which the rule's diagnostic accuracy was 77%.

They also tested a combined rule that assigned an additional 2 points to a serum antitoxin A IgG level less than 1.29 ELISA units. With a threshold of 4 points or above, this combined rule appeared promising among the derivation cohort: Of these patients, 16 had antitoxin A IgG data available. Of those, all eight patients in the high-risk group had recurrent C. difficile infection, while only one of the eight patients in the low-risk group had recurrence. In this analysis, the sensitivity of the rule was 89%, specificity was 100%, and diagnostic accuracy was 94%. This rule proved to be far less predictive in the validation cohort, in which 26 patients had antitoxin A IgG data available. Infection recurred in 3 of 6 patients in the high-risk group and 5 of 20 patients in the low-risk group. This translates to a sensitivity of 38%, specificity of 83%, and diagnostic accuracy of 69%.

The researchers advanced several hypotheses for the disappointing performance of the combined rule, including few serum samples available for antibody measurement and variations in the timing of antibody measurement. Also, the epidemiology of C. difficile infection changed between 1998 and 2004–2006.

The three-factor prediction rule for recurrence was “simple, reliable, and accurate,” according to the investigators. “This rule is valuable in clinical practice as it defines a high-risk population in whom awareness of the risk can facilitate more prompt recognition, diagnosis, and treatment of recurrent [C. difficile infection]. These patients are also most likely to benefit from interventions to prevent recurrence, such as infection control precautions [or] prudent use of antibiotics.”

The study was supported by grants from the National Institutes of Health and the Irish Health Research Board. Coauthor Dr. Ciar´n P. Kelly of Harvard Medical School acknowledged acting as a scientific consultant for and receiving research funding from several companies producing or developing treatments for C. difficile infection.

A simple new rule can be used to predict recurrence of C. difficile infection, which can cause repeated bouts of diarrhea. CDC/Dr. Gilda Jones

Many patients with Clostridium difficile infection experience repeated bouts of the illness, and a rule has been developed to accurately predict a patient's risk of recurrence, reported Dr. Mary Y. Hu and her colleagues.

The simple prediction rule takes into account a patient's age, use of antibiotics, and severity of disease. The researchers showed that the rule has a diagnostic accuracy of 72%.

These factors had been shown previously to be significant independent predictors of recurrent C. difficile diarrhea, wrote Dr. Hu of Harvard Medical School, Boston, and her colleagues. A fourth independent predictor—the serum level of antitoxin A IgG—appeared to reduce the accuracy of the rule (Gastroenterology 2009 April [doi:10.1053j.gastro.2008.12.038]).

The investigators derived the rule from a study of 63 patients hospitalized with C. difficile infection between January and May 1998, and validated it with data collected prospectively from 64 patients hospitalized between December 2004 and May 2006.

The rule assigns 1 point to each of the following three characteristics: age greater than 65 years, disease judged to be severe or fulminant in intensity, and additional antibiotic use after the discontinuation of therapy for C. difficile infection. In the validation group, recurrence occurred in 7 of 19 patients scoring 2 points or higher (37%) but in 6 of 45 patients scoring 0 or 1 (13%).

In the validation cohort, the sensitivity of the rule was 54%, the specificity was 77%, the positive predictive value was 37%, and the negative predictive value was 87%. The diagnostic accuracy was 72%. This compared favorably to the original derivation cohort, in which the rule's diagnostic accuracy was 77%.

They also tested a combined rule that assigned an additional 2 points to a serum antitoxin A IgG level less than 1.29 ELISA units. With a threshold of 4 points or above, this combined rule appeared promising among the derivation cohort: Of these patients, 16 had antitoxin A IgG data available. Of those, all eight patients in the high-risk group had recurrent C. difficile infection, while only one of the eight patients in the low-risk group had recurrence. In this analysis, the sensitivity of the rule was 89%, specificity was 100%, and diagnostic accuracy was 94%. This rule proved to be far less predictive in the validation cohort, in which 26 patients had antitoxin A IgG data available. Infection recurred in 3 of 6 patients in the high-risk group and 5 of 20 patients in the low-risk group. This translates to a sensitivity of 38%, specificity of 83%, and diagnostic accuracy of 69%.

The researchers advanced several hypotheses for the disappointing performance of the combined rule, including few serum samples available for antibody measurement and variations in the timing of antibody measurement. Also, the epidemiology of C. difficile infection changed between 1998 and 2004–2006.

The three-factor prediction rule for recurrence was “simple, reliable, and accurate,” according to the investigators. “This rule is valuable in clinical practice as it defines a high-risk population in whom awareness of the risk can facilitate more prompt recognition, diagnosis, and treatment of recurrent [C. difficile infection]. These patients are also most likely to benefit from interventions to prevent recurrence, such as infection control precautions [or] prudent use of antibiotics.”

The study was supported by grants from the National Institutes of Health and the Irish Health Research Board. Coauthor Dr. Ciar´n P. Kelly of Harvard Medical School acknowledged acting as a scientific consultant for and receiving research funding from several companies producing or developing treatments for C. difficile infection.

A simple new rule can be used to predict recurrence of C. difficile infection, which can cause repeated bouts of diarrhea. CDC/Dr. Gilda Jones

SAN FRANCISCO — Don't ignore a seemingly simple case of diaper dermatitis, because this near-ubiquitous condition can mask something much more serious.

In fact, there are at least four "zebras" whose hoof beats may be sounding in diaper dermatitis, Dr. Sheila Fallon Friedlander said at a meeting sponsored by Skin Disease Education Foundation.

That's why diaper dermatitis should be treated. Failure to respond to treatment may be your first hint that something unusual is happening.

Zinc deficiency is the first of these zebras. The baby will present with dermatitis in an acral distribution: hands, feet, face, and genitals. The parent will often mention that the baby has diarrhea and is not growing as well as she should.

If you suspect a zinc deficiency, look at alkaline phosphatase while you're waiting for zinc levels to come back from the lab. A low alkaline phosphatase level should make you suspicious of zinc, said Dr. Friedlander of the University of California, San Diego.

Langerhans cell histiocytosis (LCH) is the next zebra. Thought by many to be a clonal proliferative disorder, LCH has a wide variability in presentation and prognosis.

Dr. Friedlander described one case in which the baby had rashes in his intertriginous areas. Her first thought was Candida and, indeed, antifungals seemed to help a little bit. Adding topical steroids helped a little bit more, but the rashes never fully cleared. On top of that, the mother was noticing some small pink papules elsewhere on the baby's body.

Upon questioning, the mother noted that the baby wasn't growing very well and also was experiencing some vomiting and diarrhea. When Dr. Friedlander did a physical exam, she noticed that the baby's liver was enlarged. (Other babies with LCH have enlarged spleens.) And those pink papules? Those were purpuric papules of petechiae.

"When you see that, you need to see Red Alert," Dr. Friedlander said. "You have scaly papules; hemorrhagic, purpuric, petechial lesions; and paronychial involvement." LCH sometimes looks like seborrheic dermatitis, but the physician's job is to recognize it and refer the child to a pediatric oncologist.

The third zebra goes by the unwieldy name "recurrent toxin-mediated perineal erythema." Dr. Friedlander described one little girl with a recurrent red, scaly eruption in her groin area that never responded to the typical diaper dermatitis treatments. The mother mentioned that the eruption often was accompanied by fever and a red tongue.

"Well, certainly when we see a red tongue, we think of a toxin-mediated disorder," Dr. Friedlander said. "If the patient is febrile and looks sick, you need to get blood culture; you need to get a [sedimentation] rate. And, certainly, get cultures of the pharynx, the perianal area, and lesional skin."

Of all the zebras, Kawasaki disease is the one you least want to miss. "If you recognize it early, you can save a life," Dr. Friedlander said. The first hint often is a red perianal rash. Start worrying if you learn that the child has had a high fever for 4 or 5 days, has a strawberry tongue, and is unusually crabby.

The child with Kawasaki disease will often have conjunctivitis but of a specific type. The eye will not be purulent, and there won't be an exudate. And if you look closely, you may see that the conjunctivitis is sparing the limbus—the area where the cornea meets the sclera. The child may have cervical lymphadenopathy, and the rash can be variable. "It's pretty much a polymorphous eruption, but [it doesn't] blister," Dr. Friedlander said.

Two lab values can be especially noteworthy in Kawasaki disease. The C-reactive protein level will be 3 mg/dL or higher, and the sedimentation rate will be 40 mm/hr or more. You also should order labs to rule out pyuria, meningitis, hepatitis, hypoalbuminemia, and thrombocytosis.

Dr. Friedlander disclosed serving as a consultant and a researcher for Barrier Therapeutics Inc., which makes a prescription ointment for diaper rash.

SDEF and this newspaper are owned by Elsevier.

SAN FRANCISCO — Don't ignore a seemingly simple case of diaper dermatitis, because this near-ubiquitous condition can mask something much more serious.

In fact, there are at least four "zebras" whose hoof beats may be sounding in diaper dermatitis, Dr. Sheila Fallon Friedlander said at a meeting sponsored by Skin Disease Education Foundation.

That's why diaper dermatitis should be treated. Failure to respond to treatment may be your first hint that something unusual is happening.

Zinc deficiency is the first of these zebras. The baby will present with dermatitis in an acral distribution: hands, feet, face, and genitals. The parent will often mention that the baby has diarrhea and is not growing as well as she should.

If you suspect a zinc deficiency, look at alkaline phosphatase while you're waiting for zinc levels to come back from the lab. A low alkaline phosphatase level should make you suspicious of zinc, said Dr. Friedlander of the University of California, San Diego.

Langerhans cell histiocytosis (LCH) is the next zebra. Thought by many to be a clonal proliferative disorder, LCH has a wide variability in presentation and prognosis.

Dr. Friedlander described one case in which the baby had rashes in his intertriginous areas. Her first thought was Candida and, indeed, antifungals seemed to help a little bit. Adding topical steroids helped a little bit more, but the rashes never fully cleared. On top of that, the mother was noticing some small pink papules elsewhere on the baby's body.

Upon questioning, the mother noted that the baby wasn't growing very well and also was experiencing some vomiting and diarrhea. When Dr. Friedlander did a physical exam, she noticed that the baby's liver was enlarged. (Other babies with LCH have enlarged spleens.) And those pink papules? Those were purpuric papules of petechiae.

"When you see that, you need to see Red Alert," Dr. Friedlander said. "You have scaly papules; hemorrhagic, purpuric, petechial lesions; and paronychial involvement." LCH sometimes looks like seborrheic dermatitis, but the physician's job is to recognize it and refer the child to a pediatric oncologist.

The third zebra goes by the unwieldy name "recurrent toxin-mediated perineal erythema." Dr. Friedlander described one little girl with a recurrent red, scaly eruption in her groin area that never responded to the typical diaper dermatitis treatments. The mother mentioned that the eruption often was accompanied by fever and a red tongue.

"Well, certainly when we see a red tongue, we think of a toxin-mediated disorder," Dr. Friedlander said. "If the patient is febrile and looks sick, you need to get blood culture; you need to get a [sedimentation] rate. And, certainly, get cultures of the pharynx, the perianal area, and lesional skin."

Of all the zebras, Kawasaki disease is the one you least want to miss. "If you recognize it early, you can save a life," Dr. Friedlander said. The first hint often is a red perianal rash. Start worrying if you learn that the child has had a high fever for 4 or 5 days, has a strawberry tongue, and is unusually crabby.

The child with Kawasaki disease will often have conjunctivitis but of a specific type. The eye will not be purulent, and there won't be an exudate. And if you look closely, you may see that the conjunctivitis is sparing the limbus—the area where the cornea meets the sclera. The child may have cervical lymphadenopathy, and the rash can be variable. "It's pretty much a polymorphous eruption, but [it doesn't] blister," Dr. Friedlander said.

Two lab values can be especially noteworthy in Kawasaki disease. The C-reactive protein level will be 3 mg/dL or higher, and the sedimentation rate will be 40 mm/hr or more. You also should order labs to rule out pyuria, meningitis, hepatitis, hypoalbuminemia, and thrombocytosis.

Dr. Friedlander disclosed serving as a consultant and a researcher for Barrier Therapeutics Inc., which makes a prescription ointment for diaper rash.

SDEF and this newspaper are owned by Elsevier.

SAN FRANCISCO — Don't ignore a seemingly simple case of diaper dermatitis, because this near-ubiquitous condition can mask something much more serious.

In fact, there are at least four "zebras" whose hoof beats may be sounding in diaper dermatitis, Dr. Sheila Fallon Friedlander said at a meeting sponsored by Skin Disease Education Foundation.

That's why diaper dermatitis should be treated. Failure to respond to treatment may be your first hint that something unusual is happening.

Zinc deficiency is the first of these zebras. The baby will present with dermatitis in an acral distribution: hands, feet, face, and genitals. The parent will often mention that the baby has diarrhea and is not growing as well as she should.

If you suspect a zinc deficiency, look at alkaline phosphatase while you're waiting for zinc levels to come back from the lab. A low alkaline phosphatase level should make you suspicious of zinc, said Dr. Friedlander of the University of California, San Diego.

Langerhans cell histiocytosis (LCH) is the next zebra. Thought by many to be a clonal proliferative disorder, LCH has a wide variability in presentation and prognosis.

Dr. Friedlander described one case in which the baby had rashes in his intertriginous areas. Her first thought was Candida and, indeed, antifungals seemed to help a little bit. Adding topical steroids helped a little bit more, but the rashes never fully cleared. On top of that, the mother was noticing some small pink papules elsewhere on the baby's body.

Upon questioning, the mother noted that the baby wasn't growing very well and also was experiencing some vomiting and diarrhea. When Dr. Friedlander did a physical exam, she noticed that the baby's liver was enlarged. (Other babies with LCH have enlarged spleens.) And those pink papules? Those were purpuric papules of petechiae.

"When you see that, you need to see Red Alert," Dr. Friedlander said. "You have scaly papules; hemorrhagic, purpuric, petechial lesions; and paronychial involvement." LCH sometimes looks like seborrheic dermatitis, but the physician's job is to recognize it and refer the child to a pediatric oncologist.

The third zebra goes by the unwieldy name "recurrent toxin-mediated perineal erythema." Dr. Friedlander described one little girl with a recurrent red, scaly eruption in her groin area that never responded to the typical diaper dermatitis treatments. The mother mentioned that the eruption often was accompanied by fever and a red tongue.

"Well, certainly when we see a red tongue, we think of a toxin-mediated disorder," Dr. Friedlander said. "If the patient is febrile and looks sick, you need to get blood culture; you need to get a [sedimentation] rate. And, certainly, get cultures of the pharynx, the perianal area, and lesional skin."

Of all the zebras, Kawasaki disease is the one you least want to miss. "If you recognize it early, you can save a life," Dr. Friedlander said. The first hint often is a red perianal rash. Start worrying if you learn that the child has had a high fever for 4 or 5 days, has a strawberry tongue, and is unusually crabby.

The child with Kawasaki disease will often have conjunctivitis but of a specific type. The eye will not be purulent, and there won't be an exudate. And if you look closely, you may see that the conjunctivitis is sparing the limbus—the area where the cornea meets the sclera. The child may have cervical lymphadenopathy, and the rash can be variable. "It's pretty much a polymorphous eruption, but [it doesn't] blister," Dr. Friedlander said.

Two lab values can be especially noteworthy in Kawasaki disease. The C-reactive protein level will be 3 mg/dL or higher, and the sedimentation rate will be 40 mm/hr or more. You also should order labs to rule out pyuria, meningitis, hepatitis, hypoalbuminemia, and thrombocytosis.

Dr. Friedlander disclosed serving as a consultant and a researcher for Barrier Therapeutics Inc., which makes a prescription ointment for diaper rash.

SDEF and this newspaper are owned by Elsevier.

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

A new preparation of 5% benzoyl peroxide solubilized in a gel proved better than a 5% benzoyl peroxide/1% clindamycin preparation for treating acne vulgaris, according to the results of a poster presented at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Dr. Leon H. Kircik of Louisville, Ky., and his colleagues followed 65 patients who applied solubilized benzoyl peroxide (BPO) gel to one side of their face and BPO/clindamycin to the other side twice daily for up to 12 weeks.

The patients were aged 11-45 years and had moderate acne. The solubilized BPO gel was associated with a significant reduction in noninflammatory lesions, compared with BPO/clindamycin at weeks 1, 2, 3, 4, and 12. At week 12, for example, the solubilized BPO gel was associated with a 57% reduction in noninflammatory lesions, compared with 46% for the BPO/clindamycin. There were no differences between the products in relation to the number of inflammatory lesions.

Levels of erythema, dryness, peeling, stinging/burning, and itching were reported more by patients with the solubilized BPO gel. While this difference was statistically significant, it was not clinically significant, Dr. Kircik said in an interview. Because of these study results, “I use the solubilized BPO gel anytime I need a benzoyl peroxide,” he said.

The new preparation is proprietary and is available commercially under the brand name SoluCLENZ Rx Gel from Obagi Medical. Dr. Kircik disclosed receiving research funding from the manufacturer.

SDEF and this news organization are owned by Elsevier.

A new preparation of 5% benzoyl peroxide solubilized in a gel proved better than a 5% benzoyl peroxide/1% clindamycin preparation for treating acne vulgaris, according to the results of a poster presented at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Dr. Leon H. Kircik of Louisville, Ky., and his colleagues followed 65 patients who applied solubilized benzoyl peroxide (BPO) gel to one side of their face and BPO/clindamycin to the other side twice daily for up to 12 weeks.

The patients were aged 11-45 years and had moderate acne. The solubilized BPO gel was associated with a significant reduction in noninflammatory lesions, compared with BPO/clindamycin at weeks 1, 2, 3, 4, and 12. At week 12, for example, the solubilized BPO gel was associated with a 57% reduction in noninflammatory lesions, compared with 46% for the BPO/clindamycin. There were no differences between the products in relation to the number of inflammatory lesions.

Levels of erythema, dryness, peeling, stinging/burning, and itching were reported more by patients with the solubilized BPO gel. While this difference was statistically significant, it was not clinically significant, Dr. Kircik said in an interview. Because of these study results, “I use the solubilized BPO gel anytime I need a benzoyl peroxide,” he said.

The new preparation is proprietary and is available commercially under the brand name SoluCLENZ Rx Gel from Obagi Medical. Dr. Kircik disclosed receiving research funding from the manufacturer.

SDEF and this news organization are owned by Elsevier.

A new preparation of 5% benzoyl peroxide solubilized in a gel proved better than a 5% benzoyl peroxide/1% clindamycin preparation for treating acne vulgaris, according to the results of a poster presented at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Dr. Leon H. Kircik of Louisville, Ky., and his colleagues followed 65 patients who applied solubilized benzoyl peroxide (BPO) gel to one side of their face and BPO/clindamycin to the other side twice daily for up to 12 weeks.

The patients were aged 11-45 years and had moderate acne. The solubilized BPO gel was associated with a significant reduction in noninflammatory lesions, compared with BPO/clindamycin at weeks 1, 2, 3, 4, and 12. At week 12, for example, the solubilized BPO gel was associated with a 57% reduction in noninflammatory lesions, compared with 46% for the BPO/clindamycin. There were no differences between the products in relation to the number of inflammatory lesions.

Levels of erythema, dryness, peeling, stinging/burning, and itching were reported more by patients with the solubilized BPO gel. While this difference was statistically significant, it was not clinically significant, Dr. Kircik said in an interview. Because of these study results, “I use the solubilized BPO gel anytime I need a benzoyl peroxide,” he said.

The new preparation is proprietary and is available commercially under the brand name SoluCLENZ Rx Gel from Obagi Medical. Dr. Kircik disclosed receiving research funding from the manufacturer.

SDEF and this news organization are owned by Elsevier.

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting last fall (INTERNAL MEDICINE NEWS, Dec. 1, 2008, p. 1). The AHA also sponsored the stroke conference.

The JUPITER investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time, 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported based on the additional analysis revealed that stroke risk in the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of in the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a press briefing.

“But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So I don't think you can view stroke in isolation when making a treatment decision,” said Dr. Glynn, who is a biostatistician at the Harvard School of Public Health, Boston, and one of the coauthors of the study.

Subgroup analyses showed significant reductions in the relative risk of stroke for men but not for women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

In commenting on the results, Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., noted that “C-reactive protein is elevated generally in people who are obese and do not exercise. The question is, are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we would be treating a lot of extra people with this therapy that we may not have otherwise treated,” he observed.

“There's a really important discussion that has to happen in terms of the risks and benefits of treatment, and the cost of giving C-reactive protein tests as well,” said Dr. Bushnell, who was not affiliated with the study.

Dr. Glynn received grant support for this investigation from AstraZeneca, which manufactures rosuvastatin under the brand name Crestor.

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting last fall (INTERNAL MEDICINE NEWS, Dec. 1, 2008, p. 1). The AHA also sponsored the stroke conference.

The JUPITER investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time, 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported based on the additional analysis revealed that stroke risk in the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of in the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a press briefing.

“But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So I don't think you can view stroke in isolation when making a treatment decision,” said Dr. Glynn, who is a biostatistician at the Harvard School of Public Health, Boston, and one of the coauthors of the study.

Subgroup analyses showed significant reductions in the relative risk of stroke for men but not for women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

In commenting on the results, Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., noted that “C-reactive protein is elevated generally in people who are obese and do not exercise. The question is, are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we would be treating a lot of extra people with this therapy that we may not have otherwise treated,” he observed.

“There's a really important discussion that has to happen in terms of the risks and benefits of treatment, and the cost of giving C-reactive protein tests as well,” said Dr. Bushnell, who was not affiliated with the study.

Dr. Glynn received grant support for this investigation from AstraZeneca, which manufactures rosuvastatin under the brand name Crestor.

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting last fall (INTERNAL MEDICINE NEWS, Dec. 1, 2008, p. 1). The AHA also sponsored the stroke conference.

The JUPITER investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time, 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported based on the additional analysis revealed that stroke risk in the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of in the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a press briefing.

“But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So I don't think you can view stroke in isolation when making a treatment decision,” said Dr. Glynn, who is a biostatistician at the Harvard School of Public Health, Boston, and one of the coauthors of the study.

Subgroup analyses showed significant reductions in the relative risk of stroke for men but not for women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

In commenting on the results, Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., noted that “C-reactive protein is elevated generally in people who are obese and do not exercise. The question is, are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we would be treating a lot of extra people with this therapy that we may not have otherwise treated,” he observed.

“There's a really important discussion that has to happen in terms of the risks and benefits of treatment, and the cost of giving C-reactive protein tests as well,” said Dr. Bushnell, who was not affiliated with the study.

Dr. Glynn received grant support for this investigation from AstraZeneca, which manufactures rosuvastatin under the brand name Crestor.

SAN DIEGO — Women have strokes more often than men, but they are significantly less likely to receive the best available treatment, according to two studies presented at the International Stroke Conference.

In a meta-analysis of 18 studies involving more than 2.3 million men and women who had a stroke, Dr. Archit Bhatt of Michigan State University, East Lansing, determined that women were 30% less likely than men to receive intravenous tissue plasminogen activator (TPA), the most effective treatment known. This difference was statistically significant.

Of the 21,503 patients who received TPA, 63% were male and 37% were female.

The sex disparity persisted even after Dr. Bhatt adjusted for differences in age and other confounders. In the adjusted analysis, women were 23% less likely to receive TPA than men were (Stroke 2009 Feb. 19 [doi:10.1161/STROKEAHA.108.543181

“At this point there are no gender-based guidelines to give TPA,” Dr. Bhatt noted during a news conference. “So clearly more research needs to be done to understand the barriers to acute stroke therapy in women, so that critical health disparities can be eliminated.”

In a separate study, Dr. Louise D. McCullough of the University of Connecticut, Farmington, and her colleagues determined that on average, women arrive at the emergency department 12 minutes later than men do.

In a retrospective analysis of 435 stroke patients, aged 45 years and older, who were treated at a single emergency department, the average man arrived 96.4 minutes after the onset of symptoms, compared with 108.8 minutes for women, a significant difference.

Later arrival can have a large impact on treatment and outcome, since TPA must be administered no later than 3 hours after the onset of stroke symptoms.

“The one encouraging thing in our study that we found is that once [women] were in our emergency room, they were treated exactly the same way as men,” Dr. McCullough said at the news conference. “They were treated with the same speed, and they were treated at the same rate as men. The problem was they were losing a lot of time getting there.”

Although the data did not allow the investigators to determine why women were arriving later, Dr. McCullough offered several hypotheses.

For one thing, women tend to be older than men when they have their stroke.

In addition, a woman may be living alone, having survived her husband, and there may not be anyone available to contact authorities.

Another factor may be that “they don't have the same level of urgency that men have, and it could be they're not identifying their own atypical presentations,” Dr. McCullough said.

“I think also women tend to minimize symptoms. We've seen that in heart disease,” she added.

Dr. Bhatt and Dr. McCullough both stated that they had no conflicts of interest to disclose.

SAN DIEGO — Women have strokes more often than men, but they are significantly less likely to receive the best available treatment, according to two studies presented at the International Stroke Conference.

In a meta-analysis of 18 studies involving more than 2.3 million men and women who had a stroke, Dr. Archit Bhatt of Michigan State University, East Lansing, determined that women were 30% less likely than men to receive intravenous tissue plasminogen activator (TPA), the most effective treatment known. This difference was statistically significant.

Of the 21,503 patients who received TPA, 63% were male and 37% were female.

The sex disparity persisted even after Dr. Bhatt adjusted for differences in age and other confounders. In the adjusted analysis, women were 23% less likely to receive TPA than men were (Stroke 2009 Feb. 19 [doi:10.1161/STROKEAHA.108.543181

“At this point there are no gender-based guidelines to give TPA,” Dr. Bhatt noted during a news conference. “So clearly more research needs to be done to understand the barriers to acute stroke therapy in women, so that critical health disparities can be eliminated.”

In a separate study, Dr. Louise D. McCullough of the University of Connecticut, Farmington, and her colleagues determined that on average, women arrive at the emergency department 12 minutes later than men do.

In a retrospective analysis of 435 stroke patients, aged 45 years and older, who were treated at a single emergency department, the average man arrived 96.4 minutes after the onset of symptoms, compared with 108.8 minutes for women, a significant difference.

Later arrival can have a large impact on treatment and outcome, since TPA must be administered no later than 3 hours after the onset of stroke symptoms.

“The one encouraging thing in our study that we found is that once [women] were in our emergency room, they were treated exactly the same way as men,” Dr. McCullough said at the news conference. “They were treated with the same speed, and they were treated at the same rate as men. The problem was they were losing a lot of time getting there.”

Although the data did not allow the investigators to determine why women were arriving later, Dr. McCullough offered several hypotheses.

For one thing, women tend to be older than men when they have their stroke.

In addition, a woman may be living alone, having survived her husband, and there may not be anyone available to contact authorities.

Another factor may be that “they don't have the same level of urgency that men have, and it could be they're not identifying their own atypical presentations,” Dr. McCullough said.

“I think also women tend to minimize symptoms. We've seen that in heart disease,” she added.

Dr. Bhatt and Dr. McCullough both stated that they had no conflicts of interest to disclose.

SAN DIEGO — Women have strokes more often than men, but they are significantly less likely to receive the best available treatment, according to two studies presented at the International Stroke Conference.

In a meta-analysis of 18 studies involving more than 2.3 million men and women who had a stroke, Dr. Archit Bhatt of Michigan State University, East Lansing, determined that women were 30% less likely than men to receive intravenous tissue plasminogen activator (TPA), the most effective treatment known. This difference was statistically significant.

Of the 21,503 patients who received TPA, 63% were male and 37% were female.

The sex disparity persisted even after Dr. Bhatt adjusted for differences in age and other confounders. In the adjusted analysis, women were 23% less likely to receive TPA than men were (Stroke 2009 Feb. 19 [doi:10.1161/STROKEAHA.108.543181

“At this point there are no gender-based guidelines to give TPA,” Dr. Bhatt noted during a news conference. “So clearly more research needs to be done to understand the barriers to acute stroke therapy in women, so that critical health disparities can be eliminated.”

In a separate study, Dr. Louise D. McCullough of the University of Connecticut, Farmington, and her colleagues determined that on average, women arrive at the emergency department 12 minutes later than men do.

In a retrospective analysis of 435 stroke patients, aged 45 years and older, who were treated at a single emergency department, the average man arrived 96.4 minutes after the onset of symptoms, compared with 108.8 minutes for women, a significant difference.

Later arrival can have a large impact on treatment and outcome, since TPA must be administered no later than 3 hours after the onset of stroke symptoms.

“The one encouraging thing in our study that we found is that once [women] were in our emergency room, they were treated exactly the same way as men,” Dr. McCullough said at the news conference. “They were treated with the same speed, and they were treated at the same rate as men. The problem was they were losing a lot of time getting there.”

Although the data did not allow the investigators to determine why women were arriving later, Dr. McCullough offered several hypotheses.

For one thing, women tend to be older than men when they have their stroke.

In addition, a woman may be living alone, having survived her husband, and there may not be anyone available to contact authorities.

Another factor may be that “they don't have the same level of urgency that men have, and it could be they're not identifying their own atypical presentations,” Dr. McCullough said.

“I think also women tend to minimize symptoms. We've seen that in heart disease,” she added.

Dr. Bhatt and Dr. McCullough both stated that they had no conflicts of interest to disclose.

SAN FRANCISCO — There is no reason to be hesitant in prescribing topical retinoids to women with acne, according to Dr. Hilary E. Baldwin.

While the teratogenic potential of oral isotretinoin is well known, topical retinoids appear to be safe for use in women of childbearing potential, said Dr. Baldwin of the State University of New York, Brooklyn.

According to data from Allergan Inc., which makes Tazorac (tazarotene gel), the normal, endogenous plasma level of retinoids is 6.6 ng/mL. These retinoids come from food sources such as carrots, red peppers, sweet potatoes, and fish, she said at a meeting sponsored by Skin Disease Education Foundation. Oral isotretinoin raises this level to 862 ng/mL, according to the Accutane package insert. In contrast, tretinoin 0.1% cream raises the endogenous plasma level by only 2.9 ng/mL, tazarotene 0.1% gel by 0.14 ng/mL, and adapalene 0.1% gel (Differin) by 0.04 ng/mL, she said.

Several studies looking at women who used topical retinoids during pregnancy found no increase in developmental anomalies among offspring, even though the Food and Drug Administration classifies tazarotene as category X. “My soapbox issue is that whether or not you decide to use it in women who are actively pregnant—and that's a completely different medical-legal concern—you can't ignore half of the world population with acne simply because they happen to have a uterus,” she said. Dr. Baldwin disclosed serving as a consultant to, and being on the speakers bureau of, Allergan and several other pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO — There is no reason to be hesitant in prescribing topical retinoids to women with acne, according to Dr. Hilary E. Baldwin.

While the teratogenic potential of oral isotretinoin is well known, topical retinoids appear to be safe for use in women of childbearing potential, said Dr. Baldwin of the State University of New York, Brooklyn.

According to data from Allergan Inc., which makes Tazorac (tazarotene gel), the normal, endogenous plasma level of retinoids is 6.6 ng/mL. These retinoids come from food sources such as carrots, red peppers, sweet potatoes, and fish, she said at a meeting sponsored by Skin Disease Education Foundation. Oral isotretinoin raises this level to 862 ng/mL, according to the Accutane package insert. In contrast, tretinoin 0.1% cream raises the endogenous plasma level by only 2.9 ng/mL, tazarotene 0.1% gel by 0.14 ng/mL, and adapalene 0.1% gel (Differin) by 0.04 ng/mL, she said.

Several studies looking at women who used topical retinoids during pregnancy found no increase in developmental anomalies among offspring, even though the Food and Drug Administration classifies tazarotene as category X. “My soapbox issue is that whether or not you decide to use it in women who are actively pregnant—and that's a completely different medical-legal concern—you can't ignore half of the world population with acne simply because they happen to have a uterus,” she said. Dr. Baldwin disclosed serving as a consultant to, and being on the speakers bureau of, Allergan and several other pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO — There is no reason to be hesitant in prescribing topical retinoids to women with acne, according to Dr. Hilary E. Baldwin.

While the teratogenic potential of oral isotretinoin is well known, topical retinoids appear to be safe for use in women of childbearing potential, said Dr. Baldwin of the State University of New York, Brooklyn.

According to data from Allergan Inc., which makes Tazorac (tazarotene gel), the normal, endogenous plasma level of retinoids is 6.6 ng/mL. These retinoids come from food sources such as carrots, red peppers, sweet potatoes, and fish, she said at a meeting sponsored by Skin Disease Education Foundation. Oral isotretinoin raises this level to 862 ng/mL, according to the Accutane package insert. In contrast, tretinoin 0.1% cream raises the endogenous plasma level by only 2.9 ng/mL, tazarotene 0.1% gel by 0.14 ng/mL, and adapalene 0.1% gel (Differin) by 0.04 ng/mL, she said.

Several studies looking at women who used topical retinoids during pregnancy found no increase in developmental anomalies among offspring, even though the Food and Drug Administration classifies tazarotene as category X. “My soapbox issue is that whether or not you decide to use it in women who are actively pregnant—and that's a completely different medical-legal concern—you can't ignore half of the world population with acne simply because they happen to have a uterus,” she said. Dr. Baldwin disclosed serving as a consultant to, and being on the speakers bureau of, Allergan and several other pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented, at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting in November 2008. The AHA also sponsored the stroke conference.

Investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported here revealed that the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a news conference. “But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So you can't view stroke in isolation when making a treatment decision.” Dr. Glynn is a biostatistician at the Harvard School of Public Health, Boston, and one of the co-authors of the study.

Subgroup analyses showed significant reductions in relative risk for men but not women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., commented that “C-reactive protein is elevated generally in people who are obese and do not exercise. Are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we'll be treating a lot of extra people who may not have otherwise been treated. There's a really important discussion that has to happen in terms of the risks and benefits of treatment, as well as the cost of giving C-reactive protein tests.”

Dr. Glynn received grant support for this study from AstraZeneca, which manufactures rosuvastatin (Crestor).

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented, at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting in November 2008. The AHA also sponsored the stroke conference.

Investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported here revealed that the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a news conference. “But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So you can't view stroke in isolation when making a treatment decision.” Dr. Glynn is a biostatistician at the Harvard School of Public Health, Boston, and one of the co-authors of the study.

Subgroup analyses showed significant reductions in relative risk for men but not women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., commented that “C-reactive protein is elevated generally in people who are obese and do not exercise. Are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we'll be treating a lot of extra people who may not have otherwise been treated. There's a really important discussion that has to happen in terms of the risks and benefits of treatment, as well as the cost of giving C-reactive protein tests.”

Dr. Glynn received grant support for this study from AstraZeneca, which manufactures rosuvastatin (Crestor).

SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented, at the International Stroke Conference.

These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting in November 2008. The AHA also sponsored the stroke conference.

Investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.

The Kaplan-Meier survival analysis reported here revealed that the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.

This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.

“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a news conference. “But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So you can't view stroke in isolation when making a treatment decision.” Dr. Glynn is a biostatistician at the Harvard School of Public Health, Boston, and one of the co-authors of the study.

Subgroup analyses showed significant reductions in relative risk for men but not women, for patients with a BMI of 29.9 kg/m

The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.

Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., commented that “C-reactive protein is elevated generally in people who are obese and do not exercise. Are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we'll be treating a lot of extra people who may not have otherwise been treated. There's a really important discussion that has to happen in terms of the risks and benefits of treatment, as well as the cost of giving C-reactive protein tests.”

Dr. Glynn received grant support for this study from AstraZeneca, which manufactures rosuvastatin (Crestor).

SAN DIEGO — Patients with ischemic stroke who arrive within 1 hour of symptom onset at a hospital participating in the Get With the Guidelines-Stroke program were significantly more likely to receive thrombolytic therapy, according to a study presented at the International Stroke Conference.

Only 28% of the 106,924 patients studied arrived within that “golden hour,” said lead investigator and vascular neurologist Jeffrey L. Saver of the University of California, Los Angeles. Of those, 27% eventually received intravenous tissue plasminogen activator (tPA), compared with 13% of the patients who arrived 1–3 hours after symptom onset.

Data from prior studies suggested that 25%–30% of golden-hour patients would be eligible for tPA treatment. “We're actually doing pretty well at these hospitals,” Dr. Saver said at a news briefing at the conference sponsored by the American Heart Association, which also sponsored the study.

Rapid treatment requires a “cultural revolution,” according to Dr. Saver. “We are changing our training techniques for the new generation of physicians who are going to be interventionally minded stroke physicians. Every stroke is a treatable emergency, and it is the stroke team member's responsibility to get treatment done as soon as possible. We tell our residents, 'Push the gurney yourself to the CT scanner. Don't wait for the critical care transport nurse. Run the bloods yourself over to the lab. Run and get the tPA [from the pharmacy].'”

The study was retrospective and used data collected between 2003 and 2007 from 905 hospitals. All participating hospitals were part of the Get With the Guidelines-Stroke (GWTG-S) program, and hospital staffs were thus among the most educated on the need for the rapid treatment of people with stroke.

In the golden-hour patients, the average time to thrombolytic treatment—the “door-to-needle” (DTN) time—was 91 minutes. The average DTN for later arriving patients was significantly shorter at 77 minutes, but still longer than the recommended 60-minute target DTN time.

“We do have some room for improvement,” Dr. Saver said. “It's a natural tendency when a patient gets to the hospital early for physicians to take time to make a more considered and deliberate decision. Unfortunately, deliberation comes at the expense of brain when you treat stroke. … Time is brain. Every minute that your patient is not treated, 2 million nerve cells die. We know that every 10 minutes in which [tPA] delivery is delayed, one less patient benefits from treatment.”

In Dr. Saver's view, two factors account for the smaller proportion of late-arriving patients who receive tPA. First, some of them arrive too late for the hospital to complete all the tests before 3 hours have elapsed from the onset of symptoms. tPA is approved only for patients who can be treated within that time limit.

Second, late-arriving patients are more likely to have neurologic deficits that are predicted to be moderate rather than severe. Therefore, a fewer late-arriving patients would be expected to benefit from thrombolytic therapy. It's difficult to tease out the relative contributions of those two factors, Dr. Saver said.

Dr. Saver disclosed relationships with Concentric Medical, CoAxia, Talecris Biotherapeutics, E.E. Smith, Mitsubishi, and Boehringer Ingelheim.

SAN DIEGO — Patients with ischemic stroke who arrive within 1 hour of symptom onset at a hospital participating in the Get With the Guidelines-Stroke program were significantly more likely to receive thrombolytic therapy, according to a study presented at the International Stroke Conference.

Only 28% of the 106,924 patients studied arrived within that “golden hour,” said lead investigator and vascular neurologist Jeffrey L. Saver of the University of California, Los Angeles. Of those, 27% eventually received intravenous tissue plasminogen activator (tPA), compared with 13% of the patients who arrived 1–3 hours after symptom onset.

Data from prior studies suggested that 25%–30% of golden-hour patients would be eligible for tPA treatment. “We're actually doing pretty well at these hospitals,” Dr. Saver said at a news briefing at the conference sponsored by the American Heart Association, which also sponsored the study.

Rapid treatment requires a “cultural revolution,” according to Dr. Saver. “We are changing our training techniques for the new generation of physicians who are going to be interventionally minded stroke physicians. Every stroke is a treatable emergency, and it is the stroke team member's responsibility to get treatment done as soon as possible. We tell our residents, 'Push the gurney yourself to the CT scanner. Don't wait for the critical care transport nurse. Run the bloods yourself over to the lab. Run and get the tPA [from the pharmacy].'”

The study was retrospective and used data collected between 2003 and 2007 from 905 hospitals. All participating hospitals were part of the Get With the Guidelines-Stroke (GWTG-S) program, and hospital staffs were thus among the most educated on the need for the rapid treatment of people with stroke.

In the golden-hour patients, the average time to thrombolytic treatment—the “door-to-needle” (DTN) time—was 91 minutes. The average DTN for later arriving patients was significantly shorter at 77 minutes, but still longer than the recommended 60-minute target DTN time.

“We do have some room for improvement,” Dr. Saver said. “It's a natural tendency when a patient gets to the hospital early for physicians to take time to make a more considered and deliberate decision. Unfortunately, deliberation comes at the expense of brain when you treat stroke. … Time is brain. Every minute that your patient is not treated, 2 million nerve cells die. We know that every 10 minutes in which [tPA] delivery is delayed, one less patient benefits from treatment.”

In Dr. Saver's view, two factors account for the smaller proportion of late-arriving patients who receive tPA. First, some of them arrive too late for the hospital to complete all the tests before 3 hours have elapsed from the onset of symptoms. tPA is approved only for patients who can be treated within that time limit.

Second, late-arriving patients are more likely to have neurologic deficits that are predicted to be moderate rather than severe. Therefore, a fewer late-arriving patients would be expected to benefit from thrombolytic therapy. It's difficult to tease out the relative contributions of those two factors, Dr. Saver said.

Dr. Saver disclosed relationships with Concentric Medical, CoAxia, Talecris Biotherapeutics, E.E. Smith, Mitsubishi, and Boehringer Ingelheim.

SAN DIEGO — Patients with ischemic stroke who arrive within 1 hour of symptom onset at a hospital participating in the Get With the Guidelines-Stroke program were significantly more likely to receive thrombolytic therapy, according to a study presented at the International Stroke Conference.

Only 28% of the 106,924 patients studied arrived within that “golden hour,” said lead investigator and vascular neurologist Jeffrey L. Saver of the University of California, Los Angeles. Of those, 27% eventually received intravenous tissue plasminogen activator (tPA), compared with 13% of the patients who arrived 1–3 hours after symptom onset.

Data from prior studies suggested that 25%–30% of golden-hour patients would be eligible for tPA treatment. “We're actually doing pretty well at these hospitals,” Dr. Saver said at a news briefing at the conference sponsored by the American Heart Association, which also sponsored the study.

Rapid treatment requires a “cultural revolution,” according to Dr. Saver. “We are changing our training techniques for the new generation of physicians who are going to be interventionally minded stroke physicians. Every stroke is a treatable emergency, and it is the stroke team member's responsibility to get treatment done as soon as possible. We tell our residents, 'Push the gurney yourself to the CT scanner. Don't wait for the critical care transport nurse. Run the bloods yourself over to the lab. Run and get the tPA [from the pharmacy].'”

The study was retrospective and used data collected between 2003 and 2007 from 905 hospitals. All participating hospitals were part of the Get With the Guidelines-Stroke (GWTG-S) program, and hospital staffs were thus among the most educated on the need for the rapid treatment of people with stroke.

In the golden-hour patients, the average time to thrombolytic treatment—the “door-to-needle” (DTN) time—was 91 minutes. The average DTN for later arriving patients was significantly shorter at 77 minutes, but still longer than the recommended 60-minute target DTN time.

“We do have some room for improvement,” Dr. Saver said. “It's a natural tendency when a patient gets to the hospital early for physicians to take time to make a more considered and deliberate decision. Unfortunately, deliberation comes at the expense of brain when you treat stroke. … Time is brain. Every minute that your patient is not treated, 2 million nerve cells die. We know that every 10 minutes in which [tPA] delivery is delayed, one less patient benefits from treatment.”

In Dr. Saver's view, two factors account for the smaller proportion of late-arriving patients who receive tPA. First, some of them arrive too late for the hospital to complete all the tests before 3 hours have elapsed from the onset of symptoms. tPA is approved only for patients who can be treated within that time limit.

Second, late-arriving patients are more likely to have neurologic deficits that are predicted to be moderate rather than severe. Therefore, a fewer late-arriving patients would be expected to benefit from thrombolytic therapy. It's difficult to tease out the relative contributions of those two factors, Dr. Saver said.

Dr. Saver disclosed relationships with Concentric Medical, CoAxia, Talecris Biotherapeutics, E.E. Smith, Mitsubishi, and Boehringer Ingelheim.

SAN FRANCISCO — Patients with hepatitis C who were given prophylactic escitalopram in advance of therapy with peginterferon and ribavirin had one-third the incidence of major depression as did those who were given a placebo, according to a randomized, controlled trial.

Depression is a common and serious complication of interferon therapy, occurring in 20%–40% of patients, said Dr. Thomas Berg at the annual meeting of the American Association for the Study of Liver Diseases. He and his colleagues undertook a study to see if some of these cases of depression can be prevented.

According to DSM-IV criteria, 49% of the 96 patients taking placebo had major depressive episodes during 24 or 48 weeks of therapy with peginterferon α-2a, compared with just 14% of the 108 patients who took 10 mg of escitalopram daily, a significant difference.

There was no significant difference between the groups in sustained virologic response rates. About half the patients in each group achieved a sustained virologic response, said Dr. Berg of the Virchow Clinic at Charité Medical University of Berlin.

The patients began taking escitalopram or placebo 2 weeks before the start of antiviral therapy. That therapy consisted of 180 mcg per week of peginterferon α-2a and 800–1,200 mg of ribavirin per day. Patients with HCV type 2 or type 3 underwent treatment for 24 weeks, and those with type 1 or type 4 underwent treatment for 48 weeks. Investigators followed all patients for 72 weeks.

In addition to determining if patients met DSM-IV criteria for major depressive episodes, researchers administered the Montgomery-Åsberg Depression Rating Scale (MADRS), defining a score of 15 or greater on that scale as indicating significant depression. Patients underwent psychiatric evaluations at baseline and at weeks 4, 12, 24, 48, and 72.

Patients in either group who developed clinically relevant depression received open-label treatment with mirtazapine in addition to either placebo or escitalopram.

At baseline, the patients' mean age was 47 years, 52% were male, and the mean HCV RNA was over 1,000,000 IU/mL.

As judged by MADRS scores, 35% of patients taking placebo and 17% of patients taking escitalopram had moderate to severe depression during the course of therapy, a significant difference. Significant differences emerged starting at week 12 and lasting to week 48. As late as week 72 (24–48 weeks following the end of antiviral therapy), the difference in MADRS scores trended toward statistical significance (P = .051).

Dr. Berg has received research grants and served as an investigator, advisory board member, and speaker for Hoffman-La Roche Ltd. and Schering-Plough Inc. Hoffman-La Roche provided financial support for the study.

SAN FRANCISCO — Patients with hepatitis C who were given prophylactic escitalopram in advance of therapy with peginterferon and ribavirin had one-third the incidence of major depression as did those who were given a placebo, according to a randomized, controlled trial.

Depression is a common and serious complication of interferon therapy, occurring in 20%–40% of patients, said Dr. Thomas Berg at the annual meeting of the American Association for the Study of Liver Diseases. He and his colleagues undertook a study to see if some of these cases of depression can be prevented.

According to DSM-IV criteria, 49% of the 96 patients taking placebo had major depressive episodes during 24 or 48 weeks of therapy with peginterferon α-2a, compared with just 14% of the 108 patients who took 10 mg of escitalopram daily, a significant difference.

There was no significant difference between the groups in sustained virologic response rates. About half the patients in each group achieved a sustained virologic response, said Dr. Berg of the Virchow Clinic at Charité Medical University of Berlin.

The patients began taking escitalopram or placebo 2 weeks before the start of antiviral therapy. That therapy consisted of 180 mcg per week of peginterferon α-2a and 800–1,200 mg of ribavirin per day. Patients with HCV type 2 or type 3 underwent treatment for 24 weeks, and those with type 1 or type 4 underwent treatment for 48 weeks. Investigators followed all patients for 72 weeks.

In addition to determining if patients met DSM-IV criteria for major depressive episodes, researchers administered the Montgomery-Åsberg Depression Rating Scale (MADRS), defining a score of 15 or greater on that scale as indicating significant depression. Patients underwent psychiatric evaluations at baseline and at weeks 4, 12, 24, 48, and 72.

Patients in either group who developed clinically relevant depression received open-label treatment with mirtazapine in addition to either placebo or escitalopram.

At baseline, the patients' mean age was 47 years, 52% were male, and the mean HCV RNA was over 1,000,000 IU/mL.

As judged by MADRS scores, 35% of patients taking placebo and 17% of patients taking escitalopram had moderate to severe depression during the course of therapy, a significant difference. Significant differences emerged starting at week 12 and lasting to week 48. As late as week 72 (24–48 weeks following the end of antiviral therapy), the difference in MADRS scores trended toward statistical significance (P = .051).

Dr. Berg has received research grants and served as an investigator, advisory board member, and speaker for Hoffman-La Roche Ltd. and Schering-Plough Inc. Hoffman-La Roche provided financial support for the study.

SAN FRANCISCO — Patients with hepatitis C who were given prophylactic escitalopram in advance of therapy with peginterferon and ribavirin had one-third the incidence of major depression as did those who were given a placebo, according to a randomized, controlled trial.

Depression is a common and serious complication of interferon therapy, occurring in 20%–40% of patients, said Dr. Thomas Berg at the annual meeting of the American Association for the Study of Liver Diseases. He and his colleagues undertook a study to see if some of these cases of depression can be prevented.

According to DSM-IV criteria, 49% of the 96 patients taking placebo had major depressive episodes during 24 or 48 weeks of therapy with peginterferon α-2a, compared with just 14% of the 108 patients who took 10 mg of escitalopram daily, a significant difference.

There was no significant difference between the groups in sustained virologic response rates. About half the patients in each group achieved a sustained virologic response, said Dr. Berg of the Virchow Clinic at Charité Medical University of Berlin.

The patients began taking escitalopram or placebo 2 weeks before the start of antiviral therapy. That therapy consisted of 180 mcg per week of peginterferon α-2a and 800–1,200 mg of ribavirin per day. Patients with HCV type 2 or type 3 underwent treatment for 24 weeks, and those with type 1 or type 4 underwent treatment for 48 weeks. Investigators followed all patients for 72 weeks.

In addition to determining if patients met DSM-IV criteria for major depressive episodes, researchers administered the Montgomery-Åsberg Depression Rating Scale (MADRS), defining a score of 15 or greater on that scale as indicating significant depression. Patients underwent psychiatric evaluations at baseline and at weeks 4, 12, 24, 48, and 72.

Patients in either group who developed clinically relevant depression received open-label treatment with mirtazapine in addition to either placebo or escitalopram.

At baseline, the patients' mean age was 47 years, 52% were male, and the mean HCV RNA was over 1,000,000 IU/mL.

As judged by MADRS scores, 35% of patients taking placebo and 17% of patients taking escitalopram had moderate to severe depression during the course of therapy, a significant difference. Significant differences emerged starting at week 12 and lasting to week 48. As late as week 72 (24–48 weeks following the end of antiviral therapy), the difference in MADRS scores trended toward statistical significance (P = .051).

Dr. Berg has received research grants and served as an investigator, advisory board member, and speaker for Hoffman-La Roche Ltd. and Schering-Plough Inc. Hoffman-La Roche provided financial support for the study.