Bruce Jancin

NEW ORLEANS – Depression appears to reverse the anti-inflammatory effect of light to moderate alcohol consumption in men but not in women.

"The findings in men and women are very different. These are relatively novel findings and, honestly, I was surprised by the significant differences and the pattern of the differences. I wasn’t prepared to see this kind of a pattern," Edward C. Suarez, Ph.D., said at the annual meeting of the Society of Behavioral Medicine.

He presented the results of a cross-sectional study that examined the relationship between alcohol, depression, and C-reactive protein (CRP) in 229 adults with a mean age of 29 years and a body mass index of 25.2 kg/m². A total of 22% of subjects had mild, moderate, or significant symptoms of depression based upon their Beck Depression Inventory scores. None of the participants was a problem drinker. Indeed, 25% were nondrinkers, 32% drank alcohol infrequently, and 43% were light to moderate drinkers, meaning they consumed anywhere from three drinks per week to two drinks per day.

In both men and women, mean CRP levels were highest in former or never drinkers and lowest in light to moderate drinkers, as has consistently been found in other epidemiologic studies. The mechanism involved in alcohol’s CRP-lowering effect is unclear, but the antioxidant properties of the polyphenols in alcohol are one good possibility. What’s new in this study is the finding that depressed men who were light to moderate drinkers had a mean CRP level fully 2.5 times greater than did nondepressed men who consumed similar quantities of alcohol, according to Dr. Suarez of Duke University in Durham, N.C.

Men who were teetotalers or infrequent drinkers had similar mean CRP levels, regardless of whether they were depressed.

In contrast, mean CRP levels in depressed women who were nondrinkers were threefold higher than in nondepressed nondrinking women. Unlike the men, however, there was no significant difference in mean CRP levels between depressed and nondepressed women who were light to moderate drinkers, nor in infrequent drinkers, the psychologist continued.

All of these results held true after adjustment for age, race, blood pressure, HDL level, and physical activity. This multivariate adjustment was carried out because the nondrinkers were significantly older and heavier than the drinkers.

Because Dr. Suarez hadn’t anticipated the finding that gender differences moderated the relationship between alcohol consumption, depression, and CRP, he went looking for confirmatory data from other studies to make sure he was onto something. He found it, after a fashion, in other investigators’ earlier analysis of the U.S. National Alcohol Survey, an epidemiologic study involving 5,777 men and women featuring 11 years of follow-up for all-cause mortality, which occurred in 540 subjects (Addiction 2002:97:29-38).

This earlier study showed the same gender-based pattern that Dr. Suarez found. For men, the highest relative risk of death was in heavy drinkers who were depressed. For women, the highest risk was in former drinkers who were depressed.

The National Alcohol Survey, however, didn’t collect CRP data, but a high CRP is evidence of a systemic inflammatory state that has been linked to increased mortality from cardiovascular disease, stroke, and other causes, so the increased CRP levels seen in currently depressed subjects in his own study could have long-term adverse consequences in terms of mortality risk, he said.

Dr. Suarez reported having no financial conflicts. His study was sponsored by the National Institutes of Health.

NEW ORLEANS – Depression appears to reverse the anti-inflammatory effect of light to moderate alcohol consumption in men but not in women.

"The findings in men and women are very different. These are relatively novel findings and, honestly, I was surprised by the significant differences and the pattern of the differences. I wasn’t prepared to see this kind of a pattern," Edward C. Suarez, Ph.D., said at the annual meeting of the Society of Behavioral Medicine.

He presented the results of a cross-sectional study that examined the relationship between alcohol, depression, and C-reactive protein (CRP) in 229 adults with a mean age of 29 years and a body mass index of 25.2 kg/m². A total of 22% of subjects had mild, moderate, or significant symptoms of depression based upon their Beck Depression Inventory scores. None of the participants was a problem drinker. Indeed, 25% were nondrinkers, 32% drank alcohol infrequently, and 43% were light to moderate drinkers, meaning they consumed anywhere from three drinks per week to two drinks per day.

In both men and women, mean CRP levels were highest in former or never drinkers and lowest in light to moderate drinkers, as has consistently been found in other epidemiologic studies. The mechanism involved in alcohol’s CRP-lowering effect is unclear, but the antioxidant properties of the polyphenols in alcohol are one good possibility. What’s new in this study is the finding that depressed men who were light to moderate drinkers had a mean CRP level fully 2.5 times greater than did nondepressed men who consumed similar quantities of alcohol, according to Dr. Suarez of Duke University in Durham, N.C.

Men who were teetotalers or infrequent drinkers had similar mean CRP levels, regardless of whether they were depressed.

In contrast, mean CRP levels in depressed women who were nondrinkers were threefold higher than in nondepressed nondrinking women. Unlike the men, however, there was no significant difference in mean CRP levels between depressed and nondepressed women who were light to moderate drinkers, nor in infrequent drinkers, the psychologist continued.

All of these results held true after adjustment for age, race, blood pressure, HDL level, and physical activity. This multivariate adjustment was carried out because the nondrinkers were significantly older and heavier than the drinkers.

Because Dr. Suarez hadn’t anticipated the finding that gender differences moderated the relationship between alcohol consumption, depression, and CRP, he went looking for confirmatory data from other studies to make sure he was onto something. He found it, after a fashion, in other investigators’ earlier analysis of the U.S. National Alcohol Survey, an epidemiologic study involving 5,777 men and women featuring 11 years of follow-up for all-cause mortality, which occurred in 540 subjects (Addiction 2002:97:29-38).

This earlier study showed the same gender-based pattern that Dr. Suarez found. For men, the highest relative risk of death was in heavy drinkers who were depressed. For women, the highest risk was in former drinkers who were depressed.

The National Alcohol Survey, however, didn’t collect CRP data, but a high CRP is evidence of a systemic inflammatory state that has been linked to increased mortality from cardiovascular disease, stroke, and other causes, so the increased CRP levels seen in currently depressed subjects in his own study could have long-term adverse consequences in terms of mortality risk, he said.

Dr. Suarez reported having no financial conflicts. His study was sponsored by the National Institutes of Health.

NEW ORLEANS – Depression appears to reverse the anti-inflammatory effect of light to moderate alcohol consumption in men but not in women.

"The findings in men and women are very different. These are relatively novel findings and, honestly, I was surprised by the significant differences and the pattern of the differences. I wasn’t prepared to see this kind of a pattern," Edward C. Suarez, Ph.D., said at the annual meeting of the Society of Behavioral Medicine.

He presented the results of a cross-sectional study that examined the relationship between alcohol, depression, and C-reactive protein (CRP) in 229 adults with a mean age of 29 years and a body mass index of 25.2 kg/m². A total of 22% of subjects had mild, moderate, or significant symptoms of depression based upon their Beck Depression Inventory scores. None of the participants was a problem drinker. Indeed, 25% were nondrinkers, 32% drank alcohol infrequently, and 43% were light to moderate drinkers, meaning they consumed anywhere from three drinks per week to two drinks per day.

In both men and women, mean CRP levels were highest in former or never drinkers and lowest in light to moderate drinkers, as has consistently been found in other epidemiologic studies. The mechanism involved in alcohol’s CRP-lowering effect is unclear, but the antioxidant properties of the polyphenols in alcohol are one good possibility. What’s new in this study is the finding that depressed men who were light to moderate drinkers had a mean CRP level fully 2.5 times greater than did nondepressed men who consumed similar quantities of alcohol, according to Dr. Suarez of Duke University in Durham, N.C.

Men who were teetotalers or infrequent drinkers had similar mean CRP levels, regardless of whether they were depressed.

In contrast, mean CRP levels in depressed women who were nondrinkers were threefold higher than in nondepressed nondrinking women. Unlike the men, however, there was no significant difference in mean CRP levels between depressed and nondepressed women who were light to moderate drinkers, nor in infrequent drinkers, the psychologist continued.

All of these results held true after adjustment for age, race, blood pressure, HDL level, and physical activity. This multivariate adjustment was carried out because the nondrinkers were significantly older and heavier than the drinkers.

Because Dr. Suarez hadn’t anticipated the finding that gender differences moderated the relationship between alcohol consumption, depression, and CRP, he went looking for confirmatory data from other studies to make sure he was onto something. He found it, after a fashion, in other investigators’ earlier analysis of the U.S. National Alcohol Survey, an epidemiologic study involving 5,777 men and women featuring 11 years of follow-up for all-cause mortality, which occurred in 540 subjects (Addiction 2002:97:29-38).

This earlier study showed the same gender-based pattern that Dr. Suarez found. For men, the highest relative risk of death was in heavy drinkers who were depressed. For women, the highest risk was in former drinkers who were depressed.

The National Alcohol Survey, however, didn’t collect CRP data, but a high CRP is evidence of a systemic inflammatory state that has been linked to increased mortality from cardiovascular disease, stroke, and other causes, so the increased CRP levels seen in currently depressed subjects in his own study could have long-term adverse consequences in terms of mortality risk, he said.

Dr. Suarez reported having no financial conflicts. His study was sponsored by the National Institutes of Health.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

RALEIGH, N.C. – Absolute differences in response rates for treatments of moderate to severe plaque psoriasis as commonly used in everyday clinical practice "are small and may not be clinically significant," Dr. Joy Wan said at the annual meeting of the Society for Investigative Dermatology.

The results of a multicenter, comparative effectiveness study provide a picture of how psoriasis treatments are performing in real-world practice as opposed to the setting of clinical trials, which typically feature a nonrepresentative patient population and physician investigators having expertise in the treatment under study, according to Dr. Wan.

The results suggest that the go-to treatments for moderate to severe plaque psoriasis aren’t as effective in routine practice as they were in randomized trials (Arch. Dermatol. 2012;148:487-94). For example, only 48% of patients on adalimumab (Humira) were clear or almost clear based on Physician Global Assessment (PGA) ratings, compared with a 73% rate in an earlier clinical trial, noted Dr. Wan of the University of Pennsylvania, Philadelphia.

The comparative effectiveness study was cross sectional, and involved 713 consecutive patients with moderate to severe plaque psoriasis seen for routine follow-up care in 10 practices participating in the Dermatology Clinical Effectiveness Research Network (DCERN), a nationwide network of private and academic dermatology practices established in 2010.

The study participants (mean age, 49 years; 50% men) had a median 19-year duration of psoriasis; 23% also had psoriatic arthritis. All patients in the study were on monotherapy with methotrexate, etanercept, adalimumab, ustekinumab, or narrow-band UVB phototherapy (NBUVB). In all, 27% of the patients were on etanercept, 24% on methotrexate, 21% on adalimumab, 17% on NBUVB, and the rest on ustekinumab. Patients had been on methotrexate, adalimumab, or etanercept for a median of 12 months; ustekinumab for 4 months; and NBUVB for 2 months. On average, participants had been on only one systemic therapy or phototherapy prior to their current treatment. Patients were evaluated using PGA ratings and the Dermatology Life Quality Index.

One striking finding, noted Dr. Wan, was that recommended dosing often was not optimal. Notably, 36% of patients on etanercept were on 50 mg twice weekly and 12% on adalimumab were on 40 mg once weekly; those are double the recommended maintenance doses based on clinical trial data. And only 11% of patients on NBUVB received the optimal dosing frequency of at least 12 sessions within the previous 4 weeks.

The primary study end point was the proportion of patients rated clear or almost clear on PGA. The rates were 24% with methotrexate, 48% with adalimumab, 34% with etanercept, 36% for ustekinumab, and 28% with NBUVB.

Using methotrexate as the reference standard in analyses adjusted for more than 20 factors, including patient age, gender, and treatment duration, patients on adalimumab were 2.15-fold more likely to have clear or almost clear skin. Patients on ustekinumab were 1.57-fold more likely and those on etanercept 1.45-fold more likely to have clear or almost clear skin than those on methotrexate. The response rate to NBUVB wasn’t significantly different from that for methotrexate.

The results suggest that the biologic agents are outperforming methotrexate. That being said, the median PGA scores for all of the therapies hovered in the range of 1.3-1.7 on a scale of 0 to 5. This indicates that the absolute differences in treatment effectiveness are "quite small," Dr. Wan said. Moreover, there were no significant differences between treatments in terms of quality of life.

"The proportion of patients who said psoriasis had no or only a small effect on their quality of life was generally high across the board, ranging from 68% with narrow-band UVB to 78% with adalimumab," she said.

The number of patients who would need to be treated with a given agent in order to achieve one additional "clear" or "almost clear" response beyond what would be expected if patients were treated with methotrexate – was 4 for adalimumab, 8 for ustekinumab, 10 for etanercept, and 12 for NBUVB.

This cross-sectional study provides a useful snapshot of how psoriasis therapies are performing in current practice. The next step will be to perform a longitudinal comparative effectiveness study, according to Dr. Wan.

The DCERN network was formed in response to the fact that comparative effectiveness research was becoming a hot research trend, she said. The Institute of Medicine has identified comparative effectiveness research as a top priority, with psoriasis and acne as the main diseases of interest within dermatology.

"Congress has spent billions of dollars to jump-start comparative effectiveness research efforts," Dr. Wan noted.

Dr. Alexa B. Kimball rose from the audience to comment on the interpretation of the study data.

"There’s a relatively consistent pattern in clinical practice: Many patients are started on methotrexate; then if need be they are moved to etanercept or adalimumab, then to ustekinumab. So in a sense, since you’re finding that the clinical improvement is not so different across these therapies, doesn’t that suggest that patients get to a certain level of improvement and then are no longer switched? In fact, it may be that what you’re really showing is the level of improvement patients tend to be satisfied at," said Dr. Kimball of Harvard Medical School, Boston.

The study was sponsored by the National Institutes of Health. Dr. Wan reported having no financial conflicts. Dr. Kimball is a clinical trial investigator of biologic agents.

CHICAGO – Women with mechanical heart valves who unintentionally become pregnant while on warfarin often expect their obstetricians to recommend pregnancy termination, but that’s not what contemporary practice guidelines advocate.

Neither the latest American College of Chest Physicians guidelines (CHEST 2012;141[2 suppl]: e691S-e736S doi 10.1378/chest.11-2300) nor the European Society of Cardiology guidelines (Eur. Heart J. 2011;32:3147-97) recommend pregnancy termination under those circumstances, Dr. Anthony R. Gregg noted at the annual meeting of the American College of Cardiology.

"Studies show the risk to the fetus is fairly low overall, so there’s no recommendation for pregnancy termination," said Dr. Gregg, professor of obstetrics and gynecology, chief of maternal-fetal medicine, and director of obstetrics at the University of Florida Shands Hospital, Gainesville.

This assertion may come as a surprise to many cardiologists and primary care physicians. After all, every medical student has heard of the fetal warfarin syndrome. But while it affects about 30% of pregnancies with first-trimester warfarin exposure, the degree of severity is highly variable, he explained.

Often a woman doesn’t realize she is pregnant until weeks 6-8 of gestation or even later. The fetus has already been exposed to warfarin. Under those circumstances, the guidelines uniformly recommend that the patient with a mechanical heart valve be switched to low-molecular-weight heparin or unfractionated heparin, then returned to warfarin after 13 weeks’ gestation. She is then maintained on that well-studied oral anticoagulant until week 34, when she should once again be switched to low-molecular-weight heparin or unfractionated heparin as the time of delivery draws closer.

In the case of a planned pregnancy, the recommendation is for a patient with a mechanical valve to be on low-molecular-weight heparin or unfractionated heparin from the time of conception through 13 weeks’ gestation before switching back to warfarin. But that guidance doesn’t apply to women with the older mechanical heart valves posing maximum thromboembolic risk; those patients are best managed on warfarin continuously throughout pregnancy until the week-34 switch to low-molecular-weight heparin or unfractionated heparin.

"We try to point out to patients that they’re not out of the woods despite the fact that we’re following professional organizations’ guidelines. Sometimes they assume that since we’re following guidelines there’s no risk at all. The bottom line is warfarin can cross the placenta in pregnancy. There are lots of documented cases of fetal intracranial bleeding. We follow our patients across pregnancy looking for any evidence of warfarin-induced fetal intracranial hemorrhage," he said.

Dr. Gregg reported having no financial conflicts.

CHICAGO – Women with mechanical heart valves who unintentionally become pregnant while on warfarin often expect their obstetricians to recommend pregnancy termination, but that’s not what contemporary practice guidelines advocate.

Neither the latest American College of Chest Physicians guidelines (CHEST 2012;141[2 suppl]: e691S-e736S doi 10.1378/chest.11-2300) nor the European Society of Cardiology guidelines (Eur. Heart J. 2011;32:3147-97) recommend pregnancy termination under those circumstances, Dr. Anthony R. Gregg noted at the annual meeting of the American College of Cardiology.

"Studies show the risk to the fetus is fairly low overall, so there’s no recommendation for pregnancy termination," said Dr. Gregg, professor of obstetrics and gynecology, chief of maternal-fetal medicine, and director of obstetrics at the University of Florida Shands Hospital, Gainesville.

This assertion may come as a surprise to many cardiologists and primary care physicians. After all, every medical student has heard of the fetal warfarin syndrome. But while it affects about 30% of pregnancies with first-trimester warfarin exposure, the degree of severity is highly variable, he explained.

Often a woman doesn’t realize she is pregnant until weeks 6-8 of gestation or even later. The fetus has already been exposed to warfarin. Under those circumstances, the guidelines uniformly recommend that the patient with a mechanical heart valve be switched to low-molecular-weight heparin or unfractionated heparin, then returned to warfarin after 13 weeks’ gestation. She is then maintained on that well-studied oral anticoagulant until week 34, when she should once again be switched to low-molecular-weight heparin or unfractionated heparin as the time of delivery draws closer.

In the case of a planned pregnancy, the recommendation is for a patient with a mechanical valve to be on low-molecular-weight heparin or unfractionated heparin from the time of conception through 13 weeks’ gestation before switching back to warfarin. But that guidance doesn’t apply to women with the older mechanical heart valves posing maximum thromboembolic risk; those patients are best managed on warfarin continuously throughout pregnancy until the week-34 switch to low-molecular-weight heparin or unfractionated heparin.

"We try to point out to patients that they’re not out of the woods despite the fact that we’re following professional organizations’ guidelines. Sometimes they assume that since we’re following guidelines there’s no risk at all. The bottom line is warfarin can cross the placenta in pregnancy. There are lots of documented cases of fetal intracranial bleeding. We follow our patients across pregnancy looking for any evidence of warfarin-induced fetal intracranial hemorrhage," he said.

Dr. Gregg reported having no financial conflicts.

CHICAGO – Women with mechanical heart valves who unintentionally become pregnant while on warfarin often expect their obstetricians to recommend pregnancy termination, but that’s not what contemporary practice guidelines advocate.

Neither the latest American College of Chest Physicians guidelines (CHEST 2012;141[2 suppl]: e691S-e736S doi 10.1378/chest.11-2300) nor the European Society of Cardiology guidelines (Eur. Heart J. 2011;32:3147-97) recommend pregnancy termination under those circumstances, Dr. Anthony R. Gregg noted at the annual meeting of the American College of Cardiology.

"Studies show the risk to the fetus is fairly low overall, so there’s no recommendation for pregnancy termination," said Dr. Gregg, professor of obstetrics and gynecology, chief of maternal-fetal medicine, and director of obstetrics at the University of Florida Shands Hospital, Gainesville.

This assertion may come as a surprise to many cardiologists and primary care physicians. After all, every medical student has heard of the fetal warfarin syndrome. But while it affects about 30% of pregnancies with first-trimester warfarin exposure, the degree of severity is highly variable, he explained.

Often a woman doesn’t realize she is pregnant until weeks 6-8 of gestation or even later. The fetus has already been exposed to warfarin. Under those circumstances, the guidelines uniformly recommend that the patient with a mechanical heart valve be switched to low-molecular-weight heparin or unfractionated heparin, then returned to warfarin after 13 weeks’ gestation. She is then maintained on that well-studied oral anticoagulant until week 34, when she should once again be switched to low-molecular-weight heparin or unfractionated heparin as the time of delivery draws closer.

In the case of a planned pregnancy, the recommendation is for a patient with a mechanical valve to be on low-molecular-weight heparin or unfractionated heparin from the time of conception through 13 weeks’ gestation before switching back to warfarin. But that guidance doesn’t apply to women with the older mechanical heart valves posing maximum thromboembolic risk; those patients are best managed on warfarin continuously throughout pregnancy until the week-34 switch to low-molecular-weight heparin or unfractionated heparin.

"We try to point out to patients that they’re not out of the woods despite the fact that we’re following professional organizations’ guidelines. Sometimes they assume that since we’re following guidelines there’s no risk at all. The bottom line is warfarin can cross the placenta in pregnancy. There are lots of documented cases of fetal intracranial bleeding. We follow our patients across pregnancy looking for any evidence of warfarin-induced fetal intracranial hemorrhage," he said.

Dr. Gregg reported having no financial conflicts.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

RALEIGH, N.C. – Climate and weather can be added to the short list of factors known to influence the prevalence of atopic dermatitis, according to Dr. Jonathan I. Silverberg.

He presented a first-of-its-kind analysis in which he merged data from the Department of Health and Human Services’ 2007 National Survey of Children’s Health with state-by-state data from the National Oceanic and Atmospheric Administration’s National Climatic Data Center and the National Weather Service.

The National Survey of Children’s Health involved in-depth telephone interviews with parents in 91,642 households having one or more children under age 18 years.

Among the key findings: The prevalence of eczema was significantly lower in areas of the country with high relative humidity during the previous 2 years, especially during the months of November through April. The prevalence of eczema was also lower in areas with a high-to-extreme UV index, and with a higher-than-average outdoor air temperature, noted Dr. Silverberg of St. Luke’s–Roosevelt Hospital Center, New York.

In contrast, eczema prevalence was increased in regions with a high heating degree day index, which is a statewide, population-based measure of the energy demand needed to heat indoor structures by 1° F for 1 day using a baseline temperature of 65° F.

Children living in areas in the top tertile nationally in terms of mean relative humidity had a 20% lower risk of having eczema than did those residing in the lowest tertile. Children living in the top tertile for mean annual outdoor air temperature had a 23% lower prevalence of eczema than did those in the lowest tertile. Similarly, children living in areas with a high-to-extreme UV index, a measure which incorporates clear-sky days, had a 24% lower eczema prevalence than did children living under the condition of a low-to-moderate UV index.

Children residing in regions in the top tertile in terms of heating degree days had a 30% higher prevalence of eczema than did those living in the lowest tertile.

The most likely explanation for the effects climactic factors exert upon eczema prevalence involves the environmental impact upon skin barrier function. However, this study can’t pinpoint causality. Other possible mechanisms that might account for the observed association include vitamin D status, immune responses, or allergen exposures, according to Dr. Silverberg.

Previously established risk factors for eczema include family history, race/ethnicity, urban living, and socioeconomic status.

This study was funded in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Silverberg reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.