Mary Ann Moon

Postoperative hyperglycemia, independent of the presence of diabetes, appears to be the single most important risk factor for surgical site infection in general and colorectal procedures, according to a report in the September issue of the Archives of Surgery.

Hyperglycemia is a recognized risk for infection in cardiac and surgical intensive care units, and intensive insulin therapy is frequently used to prevent infection in those settings. This study found that serum glucose levels higher than 110 mg/dL also increased the rate of surgical site infection (SSI) in patients undergoing general and colorectal surgery and that the risk of infection rose dramatically at even higher glucose levels, said Dr. Ashar Ata and associates at Albany (N.Y.) Medical Center.

The investigators examined the relationship between hyperglycemia and SSI using information in the American College of Surgeons’ National Surgical Quality Improvement Program database. They assessed the records of 2,090 surgery patients aged 16 years and older who were treated at the medical center between 2006 and 2009.

The rate of superficial, deep incisional, or organ space infection was 1.8% among patients with postoperative glucose levels of 110 mg/dL or less. That rate rose with increasing glucose levels to a high of 17.7% in patients with levels of 220 mg/dL or higher.

Compared with patients whose first postoperative glucose level was 110 mg/dL or less, those whose first level was 111-140 mg/dL had 3.6 times the risk of developing SSI, and those whose first level was 220 mg/dL or higher had 12 times the risk.

Analysis of the subgroup of patients without diabetes showed similar results: increasing postoperative glucose levels were significantly associated with increasing risk of SSI in a dose-response fashion.

Similarly, analysis of the subgroup of patients undergoing colorectal surgery showed that postoperative serum glucose levels of 140 mg/dL or higher were the only significant predictor of surgical site infection. The rate of infection was three times higher in patients with that level of hyperglycemia (21%) than in patients with serum glucose levels below 140 mg/dL (7%).

Initial analysis showed that several other variables – including patient age, severity of illness, need for emergency surgery, need for transfusion, and operative time – also raised the risk of SSI. However, after the data were adjusted to account for serum glucose levels, all those risk factors except for operative time ceased to be significant predictors of SSI. This suggests that the effect of these other risk factors may be exerted through the alteration of serum glucose levels, Dr. Ata and colleagues said.

In contrast to the findings with general and colorectal surgery, postoperative serum glucose level showed no association with infection risk in vascular surgery. The reason for this discrepancy is not yet known, they said (Arch. Surg. 2010;145:858-64).

For vascular surgery, the rates of SSI were relatively high across all categories of serum glucose level, from 13.2% in the lowest category to 20% in the highest category. After adjustment, the likelihood of SSI in vascular surgery patients increased by 6% for every 10 minutes increase in operative time. Patients with diabetes were 1.84 times more likely to develop SSI in vascular surgery than were nondiabetic patients.

These results must be confirmed in larger, prospective, multicenter studies, the researchers noted. Meanwhile, “based on the results of this study, a revised protocol targeted at achieving glucose levels less than 140 mg/dL will be considered for a future prospective study.”

If the findings are confirmed, it is possible that clinicians may be able to reduce the risk of postsurgical infection by managing perioperative hyperglycemia, they added.

Postoperative hyperglycemia, independent of the presence of diabetes, appears to be the single most important risk factor for surgical site infection in general and colorectal procedures, according to a report in the September issue of the Archives of Surgery.

Hyperglycemia is a recognized risk for infection in cardiac and surgical intensive care units, and intensive insulin therapy is frequently used to prevent infection in those settings. This study found that serum glucose levels higher than 110 mg/dL also increased the rate of surgical site infection (SSI) in patients undergoing general and colorectal surgery and that the risk of infection rose dramatically at even higher glucose levels, said Dr. Ashar Ata and associates at Albany (N.Y.) Medical Center.

The investigators examined the relationship between hyperglycemia and SSI using information in the American College of Surgeons’ National Surgical Quality Improvement Program database. They assessed the records of 2,090 surgery patients aged 16 years and older who were treated at the medical center between 2006 and 2009.

The rate of superficial, deep incisional, or organ space infection was 1.8% among patients with postoperative glucose levels of 110 mg/dL or less. That rate rose with increasing glucose levels to a high of 17.7% in patients with levels of 220 mg/dL or higher.

Compared with patients whose first postoperative glucose level was 110 mg/dL or less, those whose first level was 111-140 mg/dL had 3.6 times the risk of developing SSI, and those whose first level was 220 mg/dL or higher had 12 times the risk.

Analysis of the subgroup of patients without diabetes showed similar results: increasing postoperative glucose levels were significantly associated with increasing risk of SSI in a dose-response fashion.

Similarly, analysis of the subgroup of patients undergoing colorectal surgery showed that postoperative serum glucose levels of 140 mg/dL or higher were the only significant predictor of surgical site infection. The rate of infection was three times higher in patients with that level of hyperglycemia (21%) than in patients with serum glucose levels below 140 mg/dL (7%).

Initial analysis showed that several other variables – including patient age, severity of illness, need for emergency surgery, need for transfusion, and operative time – also raised the risk of SSI. However, after the data were adjusted to account for serum glucose levels, all those risk factors except for operative time ceased to be significant predictors of SSI. This suggests that the effect of these other risk factors may be exerted through the alteration of serum glucose levels, Dr. Ata and colleagues said.

In contrast to the findings with general and colorectal surgery, postoperative serum glucose level showed no association with infection risk in vascular surgery. The reason for this discrepancy is not yet known, they said (Arch. Surg. 2010;145:858-64).

For vascular surgery, the rates of SSI were relatively high across all categories of serum glucose level, from 13.2% in the lowest category to 20% in the highest category. After adjustment, the likelihood of SSI in vascular surgery patients increased by 6% for every 10 minutes increase in operative time. Patients with diabetes were 1.84 times more likely to develop SSI in vascular surgery than were nondiabetic patients.

These results must be confirmed in larger, prospective, multicenter studies, the researchers noted. Meanwhile, “based on the results of this study, a revised protocol targeted at achieving glucose levels less than 140 mg/dL will be considered for a future prospective study.”

If the findings are confirmed, it is possible that clinicians may be able to reduce the risk of postsurgical infection by managing perioperative hyperglycemia, they added.

Postoperative hyperglycemia, independent of the presence of diabetes, appears to be the single most important risk factor for surgical site infection in general and colorectal procedures, according to a report in the September issue of the Archives of Surgery.

Hyperglycemia is a recognized risk for infection in cardiac and surgical intensive care units, and intensive insulin therapy is frequently used to prevent infection in those settings. This study found that serum glucose levels higher than 110 mg/dL also increased the rate of surgical site infection (SSI) in patients undergoing general and colorectal surgery and that the risk of infection rose dramatically at even higher glucose levels, said Dr. Ashar Ata and associates at Albany (N.Y.) Medical Center.

The investigators examined the relationship between hyperglycemia and SSI using information in the American College of Surgeons’ National Surgical Quality Improvement Program database. They assessed the records of 2,090 surgery patients aged 16 years and older who were treated at the medical center between 2006 and 2009.

The rate of superficial, deep incisional, or organ space infection was 1.8% among patients with postoperative glucose levels of 110 mg/dL or less. That rate rose with increasing glucose levels to a high of 17.7% in patients with levels of 220 mg/dL or higher.

Compared with patients whose first postoperative glucose level was 110 mg/dL or less, those whose first level was 111-140 mg/dL had 3.6 times the risk of developing SSI, and those whose first level was 220 mg/dL or higher had 12 times the risk.

Analysis of the subgroup of patients without diabetes showed similar results: increasing postoperative glucose levels were significantly associated with increasing risk of SSI in a dose-response fashion.

Similarly, analysis of the subgroup of patients undergoing colorectal surgery showed that postoperative serum glucose levels of 140 mg/dL or higher were the only significant predictor of surgical site infection. The rate of infection was three times higher in patients with that level of hyperglycemia (21%) than in patients with serum glucose levels below 140 mg/dL (7%).

Initial analysis showed that several other variables – including patient age, severity of illness, need for emergency surgery, need for transfusion, and operative time – also raised the risk of SSI. However, after the data were adjusted to account for serum glucose levels, all those risk factors except for operative time ceased to be significant predictors of SSI. This suggests that the effect of these other risk factors may be exerted through the alteration of serum glucose levels, Dr. Ata and colleagues said.

In contrast to the findings with general and colorectal surgery, postoperative serum glucose level showed no association with infection risk in vascular surgery. The reason for this discrepancy is not yet known, they said (Arch. Surg. 2010;145:858-64).

For vascular surgery, the rates of SSI were relatively high across all categories of serum glucose level, from 13.2% in the lowest category to 20% in the highest category. After adjustment, the likelihood of SSI in vascular surgery patients increased by 6% for every 10 minutes increase in operative time. Patients with diabetes were 1.84 times more likely to develop SSI in vascular surgery than were nondiabetic patients.

These results must be confirmed in larger, prospective, multicenter studies, the researchers noted. Meanwhile, “based on the results of this study, a revised protocol targeted at achieving glucose levels less than 140 mg/dL will be considered for a future prospective study.”

If the findings are confirmed, it is possible that clinicians may be able to reduce the risk of postsurgical infection by managing perioperative hyperglycemia, they added.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts, Worcester, and her associates.

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

This study was supported in part by the National Cancer Institute. Dr. Pagoto and her associates reported no financial conflicts of interest.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts, Worcester, and her associates.

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

This study was supported in part by the National Cancer Institute. Dr. Pagoto and her associates reported no financial conflicts of interest.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts, Worcester, and her associates.

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

This study was supported in part by the National Cancer Institute. Dr. Pagoto and her associates reported no financial conflicts of interest.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

An intervention promoting the use of a “sunless” tanning product among women at a beach reduced their sunbathing behavior and sunburns acquired for the remainder of the summer, according to a report in the September issue of the Archives of Dermatology.

The intervention also had a long-term effect, as many of the women reported that they decreased their sunbathing and used the fake tanning product again the following summer, said Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and her associates

The researchers assessed the intervention in women who visited two public beaches in Massachusetts in June and July of 2006 and agreed to participate in a study of sunbathing. A total of 125 subjects at one beach were assigned to the intervention and 125 at the other beach served as a control group. The mean age was 31 years.

The intervention included completing a brief questionnaire on sunbathing behavior, receiving written and verbal instructions on the use of a sunless tanning product and free samples of the product, receiving a pamphlet about skin cancer, having their photograph taken with an instant UV-filtered camera to demonstrate sun damage on their skin, receiving free samples of sunscreen, and being strongly encouraged to use sunless tanning rather than sunbathing. The control subjects completed the questionnaire, had their picture taken with a regular instant camera, and were given free cosmetic samples unrelated to skin health.

All study subjects had a 2-month follow-up for assessment of the short-term effects of the intervention, as well as at 1 year for long-term assessment.

At short-term follow-up, women in the intervention group reported that they had reduced their sunbathing by 33%, compared with a 10% decrease reported by the control subjects. The intervention group also said they had acquired 73% fewer sunburns, compared with 37% fewer reported by the control subjects. In addition, the intervention group said they had increased their use of protective clothing by 32%, while the control group said they had done so by only 2%. All of these between-group differences were statistically significant.

At long-term follow-up, the intervention group still reported a significant decrease in sunbathing behavior and showed a significant increase in the use of sunless tanning products, compared with the control group. The differences in the number of sunburns and the use of protective clothing did not persist.

The use of sunscreen increased slightly in both groups at short-term follow-up, but the difference between groups was not significant. And the increased use of sunscreen did not persist the following year.

These findings suggest that “promoting sunless tanning to sunbathers in the context of a skin cancer prevention public health message may be helpful in reducing sunbathing and sunburns and in promoting the use of protective clothing,” Dr. Pagoto and her colleagues wrote (Arch. Dermatol. 2010;146:979-84).

“Physicians might be reluctant to recommend sunless tanning due to concerns that it might inadvertently reinforce the patient’s desire to be tan,” they noted. However, these results suggest that instead, physicians should encourage patients who sunbathe to consider safer alternatives such as sunless tanning.

This study was limited in that nearly half of the women who were approached to participate in the study refused to do so, which could have contributed to selection bias. Also, the outcome measures relied on self-report, which may have contributed to social desirability bias. Finally, studies on the safety of the long-term use of sunless tanning products are lacking, and the long-term effects on the epidermis of dihydroxyacetone, the principal component of such products, remain unknown, the investigators noted.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.

The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.

“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.

The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.

Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.

For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).

Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.

And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.

The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.

A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.

Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.

The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.

Major Finding: High initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status.

Data Source: Plasma samples and neuropsychological tests from 880 participants in a prospective, population-based study of aging and dementia in northern Manhattan.

Disclosures: The study was funded by grants from the National Institutes of Health. The investigators had no relevant disclosures to report.

When plasma levels of beta-amyloid rise above normal and then decrease or stabilize in healthy elderly patients, it signals the onset of a rapid decline in several cognitive domains, a study has shown.

In most patients, that decline takes the form of Alzheimer's disease. In the minority who don't develop full-blown dementia, there is a marked cognitive decline that primarily affects memory rather than language or visuospatial domains, said Stephanie A. Cosentino, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, and her associates.

Studies have shown a correlation between elevated plasma beta-amyloid (Abeta) levels and the development of mild amnestic cognitive impairment or frank Alzheimer's disease (AD) within a few years. But other studies have found that decreasing, rather than elevated levels, correlate with these cognitive declines.

Dr. Cosentino's study suggests that the timing of the plasma sampling and of the subjects' disease stage may account for these discrepant results.

The investigators used data from a population-based study of aging to examine the link between plasma levels of the soluble oligomers Abeta-40 and −42 and cognitive changes. A total of 880 nondemented study subjects provided one blood sample at baseline in 1999 and a second sample 4.5 years later. They underwent a battery of neuropsychological tests at 18-month intervals.

During follow-up, 481 remained cognitively healthy, 329 developed cognitive or functional impairment but no dementia, and 70 developed AD. The cohort involved nearly equal percentages of Hispanics (37%), whites (31%), and African Americans (31%).

“Overall, high initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status,” Dr. Cosentino and her associates wrote (Arch. Neurol. 2010 Aug. 9 [doi:10.1001/archneurol.2010.189]).

Subjects whose initial Abeta-40 and Abeta-42 levels were in the top three quartiles had significantly faster cognitive decline than did those in the lowest quartile. Those with either decreasing or stable Abeta-42 levels at the second measurement had significantly faster cognitive decline than other subjects.

An elevated level of Abeta-42 at baseline predicted cognitive decline in memory, language, and visuospatial domains, with subjects in the highest quartile of beta-amyloid level consistently declining significantly faster than subjects in the lowest quartile. However, in the subgroup of subjects who remained cognitively unimpaired, those with high baseline levels of Abeta-42 showed declines only in the memory domain.

The researchers suggested that these subjects may be in the early stages of AD but have not yet shown sufficient decline in nonmemory domains to meet the criteria for dementia. Alternatively, they may remain free of dementia due to biological factors such as the ability to clear high levels of beta-amyloid or psychosocial factors such as the presence of cognitive reserve.

“Another interpretation of the association between plasma Abeta-42 and memory is that amyloid changes are an important factor in cognitive aging, independent of underlying AD. Stated differently, the observable change in both plasma Abeta and memory in this group could be a fundamentally different process than that involved in AD or might fall short of a critical threshold beyond which the full pathological presentation and clinical dementia syndrome of AD would unfold,” they wrote.

Future studies must “determine more definitively the specificity of Abeta profiles for predicting dementia vs their significance for cognitive aging more generally,” they added.

The study was funded by the National Institutes of Health. The researchers had no conflicts to report.

Major Finding: High initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status.

Data Source: Plasma samples and neuropsychological tests from 880 participants in a prospective, population-based study of aging and dementia in northern Manhattan.

Disclosures: The study was funded by grants from the National Institutes of Health. The investigators had no relevant disclosures to report.

When plasma levels of beta-amyloid rise above normal and then decrease or stabilize in healthy elderly patients, it signals the onset of a rapid decline in several cognitive domains, a study has shown.

In most patients, that decline takes the form of Alzheimer's disease. In the minority who don't develop full-blown dementia, there is a marked cognitive decline that primarily affects memory rather than language or visuospatial domains, said Stephanie A. Cosentino, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, and her associates.

Studies have shown a correlation between elevated plasma beta-amyloid (Abeta) levels and the development of mild amnestic cognitive impairment or frank Alzheimer's disease (AD) within a few years. But other studies have found that decreasing, rather than elevated levels, correlate with these cognitive declines.

Dr. Cosentino's study suggests that the timing of the plasma sampling and of the subjects' disease stage may account for these discrepant results.

The investigators used data from a population-based study of aging to examine the link between plasma levels of the soluble oligomers Abeta-40 and −42 and cognitive changes. A total of 880 nondemented study subjects provided one blood sample at baseline in 1999 and a second sample 4.5 years later. They underwent a battery of neuropsychological tests at 18-month intervals.

During follow-up, 481 remained cognitively healthy, 329 developed cognitive or functional impairment but no dementia, and 70 developed AD. The cohort involved nearly equal percentages of Hispanics (37%), whites (31%), and African Americans (31%).

“Overall, high initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status,” Dr. Cosentino and her associates wrote (Arch. Neurol. 2010 Aug. 9 [doi:10.1001/archneurol.2010.189]).

Subjects whose initial Abeta-40 and Abeta-42 levels were in the top three quartiles had significantly faster cognitive decline than did those in the lowest quartile. Those with either decreasing or stable Abeta-42 levels at the second measurement had significantly faster cognitive decline than other subjects.

An elevated level of Abeta-42 at baseline predicted cognitive decline in memory, language, and visuospatial domains, with subjects in the highest quartile of beta-amyloid level consistently declining significantly faster than subjects in the lowest quartile. However, in the subgroup of subjects who remained cognitively unimpaired, those with high baseline levels of Abeta-42 showed declines only in the memory domain.

The researchers suggested that these subjects may be in the early stages of AD but have not yet shown sufficient decline in nonmemory domains to meet the criteria for dementia. Alternatively, they may remain free of dementia due to biological factors such as the ability to clear high levels of beta-amyloid or psychosocial factors such as the presence of cognitive reserve.

“Another interpretation of the association between plasma Abeta-42 and memory is that amyloid changes are an important factor in cognitive aging, independent of underlying AD. Stated differently, the observable change in both plasma Abeta and memory in this group could be a fundamentally different process than that involved in AD or might fall short of a critical threshold beyond which the full pathological presentation and clinical dementia syndrome of AD would unfold,” they wrote.

Future studies must “determine more definitively the specificity of Abeta profiles for predicting dementia vs their significance for cognitive aging more generally,” they added.

The study was funded by the National Institutes of Health. The researchers had no conflicts to report.

Major Finding: High initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status.

Data Source: Plasma samples and neuropsychological tests from 880 participants in a prospective, population-based study of aging and dementia in northern Manhattan.

Disclosures: The study was funded by grants from the National Institutes of Health. The investigators had no relevant disclosures to report.

When plasma levels of beta-amyloid rise above normal and then decrease or stabilize in healthy elderly patients, it signals the onset of a rapid decline in several cognitive domains, a study has shown.

In most patients, that decline takes the form of Alzheimer's disease. In the minority who don't develop full-blown dementia, there is a marked cognitive decline that primarily affects memory rather than language or visuospatial domains, said Stephanie A. Cosentino, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, and her associates.

Studies have shown a correlation between elevated plasma beta-amyloid (Abeta) levels and the development of mild amnestic cognitive impairment or frank Alzheimer's disease (AD) within a few years. But other studies have found that decreasing, rather than elevated levels, correlate with these cognitive declines.

Dr. Cosentino's study suggests that the timing of the plasma sampling and of the subjects' disease stage may account for these discrepant results.

The investigators used data from a population-based study of aging to examine the link between plasma levels of the soluble oligomers Abeta-40 and −42 and cognitive changes. A total of 880 nondemented study subjects provided one blood sample at baseline in 1999 and a second sample 4.5 years later. They underwent a battery of neuropsychological tests at 18-month intervals.

During follow-up, 481 remained cognitively healthy, 329 developed cognitive or functional impairment but no dementia, and 70 developed AD. The cohort involved nearly equal percentages of Hispanics (37%), whites (31%), and African Americans (31%).

“Overall, high initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status,” Dr. Cosentino and her associates wrote (Arch. Neurol. 2010 Aug. 9 [doi:10.1001/archneurol.2010.189]).

Subjects whose initial Abeta-40 and Abeta-42 levels were in the top three quartiles had significantly faster cognitive decline than did those in the lowest quartile. Those with either decreasing or stable Abeta-42 levels at the second measurement had significantly faster cognitive decline than other subjects.

An elevated level of Abeta-42 at baseline predicted cognitive decline in memory, language, and visuospatial domains, with subjects in the highest quartile of beta-amyloid level consistently declining significantly faster than subjects in the lowest quartile. However, in the subgroup of subjects who remained cognitively unimpaired, those with high baseline levels of Abeta-42 showed declines only in the memory domain.

The researchers suggested that these subjects may be in the early stages of AD but have not yet shown sufficient decline in nonmemory domains to meet the criteria for dementia. Alternatively, they may remain free of dementia due to biological factors such as the ability to clear high levels of beta-amyloid or psychosocial factors such as the presence of cognitive reserve.

“Another interpretation of the association between plasma Abeta-42 and memory is that amyloid changes are an important factor in cognitive aging, independent of underlying AD. Stated differently, the observable change in both plasma Abeta and memory in this group could be a fundamentally different process than that involved in AD or might fall short of a critical threshold beyond which the full pathological presentation and clinical dementia syndrome of AD would unfold,” they wrote.

Future studies must “determine more definitively the specificity of Abeta profiles for predicting dementia vs their significance for cognitive aging more generally,” they added.

The study was funded by the National Institutes of Health. The researchers had no conflicts to report.

Major Finding: Sixteen percent of those in the 2 + 1 dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report in the Sept. 8 issue of JAMA.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV-7) immunization in several countries.

However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV-7 vaccine.

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV-7 in nasopharyngeal acquisition of serotype 19A,” said Dr. Elske J. M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

“In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. van Gils and her associates.

The researchers performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV-7 vaccines were first introduced.

The 948 study subjects had been randomly assigned to receive PCV-7 at ages 2 and 4 months (the 2-dose group), or PCV-7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV-7 (the unvaccinated control group).

Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, Dr. van Gils and her colleagues reported (JAMA 2010;304:1099-106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, Dr. van Gils and her colleagues noted.

One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand,” they proposed.

Major Finding: Sixteen percent of those in the 2 + 1 dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report in the Sept. 8 issue of JAMA.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV-7) immunization in several countries.

However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV-7 vaccine.

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV-7 in nasopharyngeal acquisition of serotype 19A,” said Dr. Elske J. M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

“In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. van Gils and her associates.

The researchers performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV-7 vaccines were first introduced.

The 948 study subjects had been randomly assigned to receive PCV-7 at ages 2 and 4 months (the 2-dose group), or PCV-7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV-7 (the unvaccinated control group).

Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, Dr. van Gils and her colleagues reported (JAMA 2010;304:1099-106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, Dr. van Gils and her colleagues noted.

One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand,” they proposed.

Major Finding: Sixteen percent of those in the 2 + 1 dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

Data Source: A post hoc analysis of data from a randomized controlled trial of vaccination in 948 children in the western Netherlands.

Disclosures: This study was supported by the Dutch Ministry of Health. Dr. van Gils' associates reported ties to GlaxoSmithKline, Wyeth/Pfizer, Baxter, and Novartis.

Introducing the heptavalent pneumococcal conjugant vaccine into routine infant immunization programs appears to raise the rate of nasopharyngeal acquisition of pneumococcal serotype 19A strains in the first 2 years of life, according to a report in the Sept. 8 issue of JAMA.

Researchers had noted a rapid increase in the presence of serotype 19A strains, which are often multidrug resistant, soon after the widespread implementation of heptavalent pneumococcal conjugant vaccine (PCV-7) immunization in several countries.

However, they were unsure of a definite link between the vaccine and the emergence of 19A strains because those strains have also increased in some countries without the PCV-7 vaccine.

“We now have demonstrated, to our knowledge for the first time, the facilitating role of PCV-7 in nasopharyngeal acquisition of serotype 19A,” said Dr. Elske J. M. van Gils of Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and her associates.

“In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and its observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid pneumococcal disease prevention,” said Dr. van Gils and her associates.

The researchers performed a post hoc analysis of data from a randomized controlled trial in the western Netherlands when PCV-7 vaccines were first introduced.

The 948 study subjects had been randomly assigned to receive PCV-7 at ages 2 and 4 months (the 2-dose group), or PCV-7 at ages 2, 4, and 11 months (the 2 + 1–dose group), or no PCV-7 (the unvaccinated control group).

Nasopharyngeal swabs were then obtained at ages 6 weeks and 6, 12, 18, and 24 months to test for the presence of S. pneumoniae and its susceptibility to antibiotics.

The cumulative proportion of children with serotype 19A was significantly higher at the age of 12 and 18 months in both the 2-dose and 2 + 1–dose groups than in the unvaccinated group, but not at 6 months, Dr. van Gils and her colleagues reported (JAMA 2010;304:1099-106).

Sixteen percent of those in the 2 + 1–dose group tested positive for new serotype 19A acquisition, which was significantly higher than the 9% rate in the control group; 13% of children in the 2-dose group did so, but this was not significantly higher than in the control group.

This included the diffuse proliferation of several serotype 19A strains as well as the appearance of new strains.

“Antibiotic resistance or antibiotic consumption could not account for the observed increase,” as both resistance and use of antibiotics were extremely low in this population, Dr. van Gils and her colleagues noted.

One possible explanation is that the reduction in colonization of covered serotypes after vaccination “creates a vacant nasopharyngeal niche where other nonvaccine serotypes, in particular certain 19A clones, may expand,” they proposed.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.

The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.

Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.

Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.

Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.

The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.

Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.

It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).

The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.

Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.

Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.

More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.

Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.

“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.

Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.

“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.

This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.

Insulin resistance in cognitively normal subjects is associated with a pattern of reduced regional cerebral glucose metabolism that is characteristic of mild cognitive impairment and early Alzheimer’s disease, according to a study published online Sept. 13 in the Archives of Neurology.

On PET scanning, subjects with insulin resistance also showed an unusual activation pattern in the brain during a memory encoding task. This coincided with their poorer performance in recalling words, compared with healthy adults who were not insulin resistant.

“Taken together, these results suggest that increased insulin resistance may be a marker of AD [Alzheimer’s disease] risk that is associated with reduced regional cerebral glucose metabolism and subtle cognitive impairments at the earliest stage of disease, even before the onset of MCI [mild cognitive impairment],” wrote Laura D. Baker, Ph.D., of the Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, and her associates.

Since insulin resistance is known to cause type 2 diabetes and to raise the risk of Alzheimer’s disease, Dr. Baker and her colleagues tested the hypothesis that cognitively normal adults with newly diagnosed prediabetes or type 2 diabetes and insulin resistance would already show abnormal cerebral glucose metabolism in regions known to predict susceptibility to AD.

The study subjects were adults with newly diagnosed, as-yet untreated prediabetes (11 patients) or type 2 diabetes (12 patients) – all of whom had insulin resistance – as well as a control group of 6 adults matched for age and education level who had normal glucose values and no insulin resistance. The subjects underwent PET imaging in a resting state and during a 35-minute memory-encoding task, and were tested for delayed free recall after the scanning was completed.

Insulin resistance was associated with reduced glucose metabolism in the posterior cingulate cortex, precuneus region, parietal cortices, temporal/angular gyri, and anterior and inferior prefrontal cortices. In contrast, no such impairment was seen in the control subjects.

“This pattern of hypometabolism has also been observed in patients with MCI and AD, in middle-aged carriers of the APOE e4 genetic risk factor who do not have dementia, and in presymptomatic adults with the AD-causative presenilin-1 gene,” Dr. Baker and her colleagues wrote (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.225]).

The link between insulin resistance and reduced glucose metabolism in this study was not affected by subjects’ age, fasting glucose values obtained just before PET scanning, degree of hyperglycemia after oral glucose tolerance testing, or APOE e4 allele status.

In addition, patients with insulin resistance showed a diffuse rather than a more focused pattern of brain activation during the memory encoding task, including activation of areas adjacent to the regions that were activated in the control group. They also showed activation or hyperactivation of areas “not typically engaged in a cognitive task,” a finding that has been reported in patients with prodromal or early AD and non-symptomatic carriers of the APOE e4 allele. This pattern may represent “a compensatory mechanism invoked following dysfunction of the neuroarchitectural network that typically would support a cognitive task,” the researchers noted.

Although the insulin-resistant subjects were not cognitively impaired according to current criteria, their recall ability was poorer than was that of the control group in the post-scanning test.

This study was limited by its small sample size, according to Dr. Baker and her associates. “Clearly, our results need to be replicated with a larger sample.”

This study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and by the U.S. Department of Veterans Affairs. The investigators reported no financial conflicts of interest.

Insulin resistance in cognitively normal subjects is associated with a pattern of reduced regional cerebral glucose metabolism that is characteristic of mild cognitive impairment and early Alzheimer’s disease, according to a study published online Sept. 13 in the Archives of Neurology.

On PET scanning, subjects with insulin resistance also showed an unusual activation pattern in the brain during a memory encoding task. This coincided with their poorer performance in recalling words, compared with healthy adults who were not insulin resistant.

“Taken together, these results suggest that increased insulin resistance may be a marker of AD [Alzheimer’s disease] risk that is associated with reduced regional cerebral glucose metabolism and subtle cognitive impairments at the earliest stage of disease, even before the onset of MCI [mild cognitive impairment],” wrote Laura D. Baker, Ph.D., of the Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, and her associates.

Since insulin resistance is known to cause type 2 diabetes and to raise the risk of Alzheimer’s disease, Dr. Baker and her colleagues tested the hypothesis that cognitively normal adults with newly diagnosed prediabetes or type 2 diabetes and insulin resistance would already show abnormal cerebral glucose metabolism in regions known to predict susceptibility to AD.

The study subjects were adults with newly diagnosed, as-yet untreated prediabetes (11 patients) or type 2 diabetes (12 patients) – all of whom had insulin resistance – as well as a control group of 6 adults matched for age and education level who had normal glucose values and no insulin resistance. The subjects underwent PET imaging in a resting state and during a 35-minute memory-encoding task, and were tested for delayed free recall after the scanning was completed.

Insulin resistance was associated with reduced glucose metabolism in the posterior cingulate cortex, precuneus region, parietal cortices, temporal/angular gyri, and anterior and inferior prefrontal cortices. In contrast, no such impairment was seen in the control subjects.

“This pattern of hypometabolism has also been observed in patients with MCI and AD, in middle-aged carriers of the APOE e4 genetic risk factor who do not have dementia, and in presymptomatic adults with the AD-causative presenilin-1 gene,” Dr. Baker and her colleagues wrote (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.225]).

The link between insulin resistance and reduced glucose metabolism in this study was not affected by subjects’ age, fasting glucose values obtained just before PET scanning, degree of hyperglycemia after oral glucose tolerance testing, or APOE e4 allele status.

In addition, patients with insulin resistance showed a diffuse rather than a more focused pattern of brain activation during the memory encoding task, including activation of areas adjacent to the regions that were activated in the control group. They also showed activation or hyperactivation of areas “not typically engaged in a cognitive task,” a finding that has been reported in patients with prodromal or early AD and non-symptomatic carriers of the APOE e4 allele. This pattern may represent “a compensatory mechanism invoked following dysfunction of the neuroarchitectural network that typically would support a cognitive task,” the researchers noted.

Although the insulin-resistant subjects were not cognitively impaired according to current criteria, their recall ability was poorer than was that of the control group in the post-scanning test.

This study was limited by its small sample size, according to Dr. Baker and her associates. “Clearly, our results need to be replicated with a larger sample.”

This study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and by the U.S. Department of Veterans Affairs. The investigators reported no financial conflicts of interest.

Insulin resistance in cognitively normal subjects is associated with a pattern of reduced regional cerebral glucose metabolism that is characteristic of mild cognitive impairment and early Alzheimer’s disease, according to a study published online Sept. 13 in the Archives of Neurology.

On PET scanning, subjects with insulin resistance also showed an unusual activation pattern in the brain during a memory encoding task. This coincided with their poorer performance in recalling words, compared with healthy adults who were not insulin resistant.

“Taken together, these results suggest that increased insulin resistance may be a marker of AD [Alzheimer’s disease] risk that is associated with reduced regional cerebral glucose metabolism and subtle cognitive impairments at the earliest stage of disease, even before the onset of MCI [mild cognitive impairment],” wrote Laura D. Baker, Ph.D., of the Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, and her associates.

Since insulin resistance is known to cause type 2 diabetes and to raise the risk of Alzheimer’s disease, Dr. Baker and her colleagues tested the hypothesis that cognitively normal adults with newly diagnosed prediabetes or type 2 diabetes and insulin resistance would already show abnormal cerebral glucose metabolism in regions known to predict susceptibility to AD.

The study subjects were adults with newly diagnosed, as-yet untreated prediabetes (11 patients) or type 2 diabetes (12 patients) – all of whom had insulin resistance – as well as a control group of 6 adults matched for age and education level who had normal glucose values and no insulin resistance. The subjects underwent PET imaging in a resting state and during a 35-minute memory-encoding task, and were tested for delayed free recall after the scanning was completed.

Insulin resistance was associated with reduced glucose metabolism in the posterior cingulate cortex, precuneus region, parietal cortices, temporal/angular gyri, and anterior and inferior prefrontal cortices. In contrast, no such impairment was seen in the control subjects.

“This pattern of hypometabolism has also been observed in patients with MCI and AD, in middle-aged carriers of the APOE e4 genetic risk factor who do not have dementia, and in presymptomatic adults with the AD-causative presenilin-1 gene,” Dr. Baker and her colleagues wrote (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.225]).

The link between insulin resistance and reduced glucose metabolism in this study was not affected by subjects’ age, fasting glucose values obtained just before PET scanning, degree of hyperglycemia after oral glucose tolerance testing, or APOE e4 allele status.

In addition, patients with insulin resistance showed a diffuse rather than a more focused pattern of brain activation during the memory encoding task, including activation of areas adjacent to the regions that were activated in the control group. They also showed activation or hyperactivation of areas “not typically engaged in a cognitive task,” a finding that has been reported in patients with prodromal or early AD and non-symptomatic carriers of the APOE e4 allele. This pattern may represent “a compensatory mechanism invoked following dysfunction of the neuroarchitectural network that typically would support a cognitive task,” the researchers noted.

Although the insulin-resistant subjects were not cognitively impaired according to current criteria, their recall ability was poorer than was that of the control group in the post-scanning test.

This study was limited by its small sample size, according to Dr. Baker and her associates. “Clearly, our results need to be replicated with a larger sample.”

This study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and by the U.S. Department of Veterans Affairs. The investigators reported no financial conflicts of interest.