Mary Ann Moon

Regular aspirin use has been linked to a lower risk of BRAF wild-type, but not BRAF mutated, colorectal cancer, according to a report in the June 26 issue of JAMA.

The absolute difference in risk was considered modest, so further investigation is required to clarify the clinical implications of these study findings. But the results do indicate that BRAF status may someday serve as a marker of sensitivity to aspirin therapy, said Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute and Harvard University, Boston, and her associates.

Activating mutations in the BRAF oncogene occur in 10%-15% of colorectal cancers, and are thought to play a role in the upregulation and synthesis of certain prostaglandins. Since aspirin is an antiprostaglandin, "we hypothesized that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin, whereas BRAF wild-type neoplastic cells might be more susceptible to its antitumor effects," they said.

© Darren Hester/Fotolia.com

The study findings also could lead to new treatment strategies that are better tailored to tumor characteristics. And they "enhance understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects," the investigators noted.

Dr. Nishihara and her colleagues examined the association between aspirin use and colorectal cancer’s BRAF mutation status using data from two large national prospective cohort studies that tracked participants’ aspirin use beginning in the 1980s. They analyzed data on 82,095 women in the Nurses' Health Study (NHS) and 45,770 men in the Health Professionals Follow-Up Study (HPFS), in which numerous dietary and other exposures were monitored in detail at 2-year intervals.

"Our detailed, updated exposure data allowed us to control for the effects of potential confounding by other dietary and lifestyle factors implicated in colorectal carcinogenesis," they said.

The study participants used aspirin primarily to prevent cardiovascular disease and to treat arthritis, other musculoskeletal pain, and headache.

During 28 years (more than 3 million person-years) of follow-up, 1,226 of these subjects developed colorectal cancer. As expected, both men and women who used aspirin regularly showed a significantly lower risk of developing the disease than did aspirin nonusers.

DNA tissue was extracted from stored samples of tumor tissue so that BRAF status could be determined.

Aspirin use was associated with a significantly lower risk of BRAF-wild-type cancer. For this tumor, the age-adjusted incidence was 40.2 per 100,000 person-years among aspirin nonusers, compared with 30.5 per 100,000 person-years for aspirin users.

In contrast, aspirin use showed no relation to the risk of BRAF-mutated cancer. The age-adjusted incidence was 5.0 per 100,000 person-years among nonusers and 5.7 per 100,000 among aspirin users (JAMA 2013;309:2563-71).

In a sensitivity analysis that accounted for the concomitant use of cholesterol-lowering agents, antihypertensive medications, and NSAIDs, the results were unchanged.

Further investigation showed that the risk of BRAF-wild-type colorectal cancer decreased as the weekly dose of aspirin increased. In addition, this risk decreased as the duration of aspirin therapy increased.

In contrast, neither dose nor duration of aspirin therapy affected the risk for BRAF-mutated cancer.

"These findings support the hypothesis that BRAF-mutated cells may show resistance to the anticancer effects of aspirin due to upregulation of the [prostaglandin] pathway," Dr. Nishihara and her associates said.

This study was supported by the National Institutes of Health, the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance. Dr. Nishihara reported no financial conflicts. An associate reported ties to Bayer Healthcare, Millenium Pharmaceuticals, Pfizer, and Pozen.

Regular aspirin use has been linked to a lower risk of BRAF wild-type, but not BRAF mutated, colorectal cancer, according to a report in the June 26 issue of JAMA.

The absolute difference in risk was considered modest, so further investigation is required to clarify the clinical implications of these study findings. But the results do indicate that BRAF status may someday serve as a marker of sensitivity to aspirin therapy, said Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute and Harvard University, Boston, and her associates.

Activating mutations in the BRAF oncogene occur in 10%-15% of colorectal cancers, and are thought to play a role in the upregulation and synthesis of certain prostaglandins. Since aspirin is an antiprostaglandin, "we hypothesized that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin, whereas BRAF wild-type neoplastic cells might be more susceptible to its antitumor effects," they said.

© Darren Hester/Fotolia.com

The study findings also could lead to new treatment strategies that are better tailored to tumor characteristics. And they "enhance understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects," the investigators noted.

Dr. Nishihara and her colleagues examined the association between aspirin use and colorectal cancer’s BRAF mutation status using data from two large national prospective cohort studies that tracked participants’ aspirin use beginning in the 1980s. They analyzed data on 82,095 women in the Nurses' Health Study (NHS) and 45,770 men in the Health Professionals Follow-Up Study (HPFS), in which numerous dietary and other exposures were monitored in detail at 2-year intervals.

"Our detailed, updated exposure data allowed us to control for the effects of potential confounding by other dietary and lifestyle factors implicated in colorectal carcinogenesis," they said.

The study participants used aspirin primarily to prevent cardiovascular disease and to treat arthritis, other musculoskeletal pain, and headache.

During 28 years (more than 3 million person-years) of follow-up, 1,226 of these subjects developed colorectal cancer. As expected, both men and women who used aspirin regularly showed a significantly lower risk of developing the disease than did aspirin nonusers.

DNA tissue was extracted from stored samples of tumor tissue so that BRAF status could be determined.

Aspirin use was associated with a significantly lower risk of BRAF-wild-type cancer. For this tumor, the age-adjusted incidence was 40.2 per 100,000 person-years among aspirin nonusers, compared with 30.5 per 100,000 person-years for aspirin users.

In contrast, aspirin use showed no relation to the risk of BRAF-mutated cancer. The age-adjusted incidence was 5.0 per 100,000 person-years among nonusers and 5.7 per 100,000 among aspirin users (JAMA 2013;309:2563-71).

In a sensitivity analysis that accounted for the concomitant use of cholesterol-lowering agents, antihypertensive medications, and NSAIDs, the results were unchanged.

Further investigation showed that the risk of BRAF-wild-type colorectal cancer decreased as the weekly dose of aspirin increased. In addition, this risk decreased as the duration of aspirin therapy increased.

In contrast, neither dose nor duration of aspirin therapy affected the risk for BRAF-mutated cancer.

"These findings support the hypothesis that BRAF-mutated cells may show resistance to the anticancer effects of aspirin due to upregulation of the [prostaglandin] pathway," Dr. Nishihara and her associates said.

This study was supported by the National Institutes of Health, the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance. Dr. Nishihara reported no financial conflicts. An associate reported ties to Bayer Healthcare, Millenium Pharmaceuticals, Pfizer, and Pozen.

Regular aspirin use has been linked to a lower risk of BRAF wild-type, but not BRAF mutated, colorectal cancer, according to a report in the June 26 issue of JAMA.

The absolute difference in risk was considered modest, so further investigation is required to clarify the clinical implications of these study findings. But the results do indicate that BRAF status may someday serve as a marker of sensitivity to aspirin therapy, said Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute and Harvard University, Boston, and her associates.

Activating mutations in the BRAF oncogene occur in 10%-15% of colorectal cancers, and are thought to play a role in the upregulation and synthesis of certain prostaglandins. Since aspirin is an antiprostaglandin, "we hypothesized that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin, whereas BRAF wild-type neoplastic cells might be more susceptible to its antitumor effects," they said.

© Darren Hester/Fotolia.com

The study findings also could lead to new treatment strategies that are better tailored to tumor characteristics. And they "enhance understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects," the investigators noted.

Dr. Nishihara and her colleagues examined the association between aspirin use and colorectal cancer’s BRAF mutation status using data from two large national prospective cohort studies that tracked participants’ aspirin use beginning in the 1980s. They analyzed data on 82,095 women in the Nurses' Health Study (NHS) and 45,770 men in the Health Professionals Follow-Up Study (HPFS), in which numerous dietary and other exposures were monitored in detail at 2-year intervals.

"Our detailed, updated exposure data allowed us to control for the effects of potential confounding by other dietary and lifestyle factors implicated in colorectal carcinogenesis," they said.

The study participants used aspirin primarily to prevent cardiovascular disease and to treat arthritis, other musculoskeletal pain, and headache.

During 28 years (more than 3 million person-years) of follow-up, 1,226 of these subjects developed colorectal cancer. As expected, both men and women who used aspirin regularly showed a significantly lower risk of developing the disease than did aspirin nonusers.

DNA tissue was extracted from stored samples of tumor tissue so that BRAF status could be determined.

Aspirin use was associated with a significantly lower risk of BRAF-wild-type cancer. For this tumor, the age-adjusted incidence was 40.2 per 100,000 person-years among aspirin nonusers, compared with 30.5 per 100,000 person-years for aspirin users.

In contrast, aspirin use showed no relation to the risk of BRAF-mutated cancer. The age-adjusted incidence was 5.0 per 100,000 person-years among nonusers and 5.7 per 100,000 among aspirin users (JAMA 2013;309:2563-71).

In a sensitivity analysis that accounted for the concomitant use of cholesterol-lowering agents, antihypertensive medications, and NSAIDs, the results were unchanged.

Further investigation showed that the risk of BRAF-wild-type colorectal cancer decreased as the weekly dose of aspirin increased. In addition, this risk decreased as the duration of aspirin therapy increased.

In contrast, neither dose nor duration of aspirin therapy affected the risk for BRAF-mutated cancer.

"These findings support the hypothesis that BRAF-mutated cells may show resistance to the anticancer effects of aspirin due to upregulation of the [prostaglandin] pathway," Dr. Nishihara and her associates said.

This study was supported by the National Institutes of Health, the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance. Dr. Nishihara reported no financial conflicts. An associate reported ties to Bayer Healthcare, Millenium Pharmaceuticals, Pfizer, and Pozen.

The use of the most advanced technologies for treating prostate cancer, such as intensity-modulated radiotherapy and robotic prostatectomy, is common and increasing among the very men least likely to benefit from treatment, according to a report published June 26 in JAMA.

In a retrospective cohort study involving nearly 56,000 men newly diagnosed with prostate cancer during a recent 5-year period, advanced treatment technologies steadily supplanted more conservative approaches in older men who had low-risk disease, a high risk of dying from some other cause, or both, said Dr. Bruce L. Jacobs of the University of Michigan, Ann Arbor, and his associates (JAMA 2013;309:2587-95).

Paradoxically, this increase occurred against a backdrop of "increasing awareness about the indolent nature of some prostate cancers and of growing dialogue about limiting treatment in these patients," the researchers noted.

"Our findings suggest that, even during this period of enhanced stewardship, incentives favoring the diffusion of these technologies outweighed those related to implementing a more conservative management strategy," they said.

Dr. Jacobs and his colleagues examined this issue using data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database after noting the rapid growth in the use of advanced treatment technologies, as well as the aggressive direct-to-consumer marketing and other "incentives" propelling that growth. They identified men aged 66 years and older whose prostate cancer was diagnosed during a 5-year period and who were followed for 1-6 years afterward.

The study population comprised 23,633 men who underwent intensity-modulated radiotherapy (IMRT) and 5,881 who had robotic prostatectomy, who were compared with 3,926 men who underwent traditional external-beam radiation therapy, 6,123 who had open radical prostatectomy, and 16,384 who opted for watchful waiting (observation).

The investigators estimated the study subjects’ probability of dying within 10 years based on age, race, comorbidity, socioeconomic class, type of residence (urban or rural), and the region of the country in which they lived.

As expected, the use of the advanced technologies increased over time in the entire study population. But it also increased among the men who "stood to gain the least in terms of survival."

During the 5-year study period, the use of both IMRT and robotic prostatectomy increased from 32% to 44% of men who had low-risk disease based on the clinical stage of their tumor, Gleason score, and prostate-specific antigen (PSA) level. The use of both also increased from 36% to 57% of men who were at high risk of dying from another cause. And it rose from 25% to 34% of men who had both low-risk disease and a high risk of noncancer mortality.

At the same time, the use of more conservative approaches declined to a similar degree in these low-risk patients.

In a further analysis of the data, the use of advanced treatment technologies in men who were the most unlikely to die of prostate cancer increased from 13% at the start of the 5-year period to 24% at the end, a relative increase of 85%, Dr. Jacobs and his associates said.

These trends are particularly concerning because both IMRT and robotic prostatectomy are considerably more expensive than the less aggressive approaches they are displacing, the researchers added.

Some clinicians and patients may believe that the more advanced technologies yield better outcomes, but "comparative studies have shown that the advantages of these newer treatments are marginal at best," Dr. Jacobs and his colleagues said.

"More diligence is needed to reduce the potentially unnecessary treatment of men with a low risk of dying from prostate cancer," they said.

The study was supported by the American Cancer Society, the National Institutes of Health, Blue Cross Blue Shield of Michigan, and the National Cancer Institute. Dr. Jacobs reported no financial conflicts of interest, and two of his associates reported ties to ArborMetrix and HistoSonics.

The use of the most advanced technologies for treating prostate cancer, such as intensity-modulated radiotherapy and robotic prostatectomy, is common and increasing among the very men least likely to benefit from treatment, according to a report published June 26 in JAMA.

In a retrospective cohort study involving nearly 56,000 men newly diagnosed with prostate cancer during a recent 5-year period, advanced treatment technologies steadily supplanted more conservative approaches in older men who had low-risk disease, a high risk of dying from some other cause, or both, said Dr. Bruce L. Jacobs of the University of Michigan, Ann Arbor, and his associates (JAMA 2013;309:2587-95).

Paradoxically, this increase occurred against a backdrop of "increasing awareness about the indolent nature of some prostate cancers and of growing dialogue about limiting treatment in these patients," the researchers noted.

"Our findings suggest that, even during this period of enhanced stewardship, incentives favoring the diffusion of these technologies outweighed those related to implementing a more conservative management strategy," they said.

Dr. Jacobs and his colleagues examined this issue using data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database after noting the rapid growth in the use of advanced treatment technologies, as well as the aggressive direct-to-consumer marketing and other "incentives" propelling that growth. They identified men aged 66 years and older whose prostate cancer was diagnosed during a 5-year period and who were followed for 1-6 years afterward.

The study population comprised 23,633 men who underwent intensity-modulated radiotherapy (IMRT) and 5,881 who had robotic prostatectomy, who were compared with 3,926 men who underwent traditional external-beam radiation therapy, 6,123 who had open radical prostatectomy, and 16,384 who opted for watchful waiting (observation).

The investigators estimated the study subjects’ probability of dying within 10 years based on age, race, comorbidity, socioeconomic class, type of residence (urban or rural), and the region of the country in which they lived.

As expected, the use of the advanced technologies increased over time in the entire study population. But it also increased among the men who "stood to gain the least in terms of survival."

During the 5-year study period, the use of both IMRT and robotic prostatectomy increased from 32% to 44% of men who had low-risk disease based on the clinical stage of their tumor, Gleason score, and prostate-specific antigen (PSA) level. The use of both also increased from 36% to 57% of men who were at high risk of dying from another cause. And it rose from 25% to 34% of men who had both low-risk disease and a high risk of noncancer mortality.

At the same time, the use of more conservative approaches declined to a similar degree in these low-risk patients.

In a further analysis of the data, the use of advanced treatment technologies in men who were the most unlikely to die of prostate cancer increased from 13% at the start of the 5-year period to 24% at the end, a relative increase of 85%, Dr. Jacobs and his associates said.

These trends are particularly concerning because both IMRT and robotic prostatectomy are considerably more expensive than the less aggressive approaches they are displacing, the researchers added.

Some clinicians and patients may believe that the more advanced technologies yield better outcomes, but "comparative studies have shown that the advantages of these newer treatments are marginal at best," Dr. Jacobs and his colleagues said.

"More diligence is needed to reduce the potentially unnecessary treatment of men with a low risk of dying from prostate cancer," they said.

The study was supported by the American Cancer Society, the National Institutes of Health, Blue Cross Blue Shield of Michigan, and the National Cancer Institute. Dr. Jacobs reported no financial conflicts of interest, and two of his associates reported ties to ArborMetrix and HistoSonics.

The use of the most advanced technologies for treating prostate cancer, such as intensity-modulated radiotherapy and robotic prostatectomy, is common and increasing among the very men least likely to benefit from treatment, according to a report published June 26 in JAMA.

In a retrospective cohort study involving nearly 56,000 men newly diagnosed with prostate cancer during a recent 5-year period, advanced treatment technologies steadily supplanted more conservative approaches in older men who had low-risk disease, a high risk of dying from some other cause, or both, said Dr. Bruce L. Jacobs of the University of Michigan, Ann Arbor, and his associates (JAMA 2013;309:2587-95).

Paradoxically, this increase occurred against a backdrop of "increasing awareness about the indolent nature of some prostate cancers and of growing dialogue about limiting treatment in these patients," the researchers noted.

"Our findings suggest that, even during this period of enhanced stewardship, incentives favoring the diffusion of these technologies outweighed those related to implementing a more conservative management strategy," they said.

Dr. Jacobs and his colleagues examined this issue using data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database after noting the rapid growth in the use of advanced treatment technologies, as well as the aggressive direct-to-consumer marketing and other "incentives" propelling that growth. They identified men aged 66 years and older whose prostate cancer was diagnosed during a 5-year period and who were followed for 1-6 years afterward.

The study population comprised 23,633 men who underwent intensity-modulated radiotherapy (IMRT) and 5,881 who had robotic prostatectomy, who were compared with 3,926 men who underwent traditional external-beam radiation therapy, 6,123 who had open radical prostatectomy, and 16,384 who opted for watchful waiting (observation).

The investigators estimated the study subjects’ probability of dying within 10 years based on age, race, comorbidity, socioeconomic class, type of residence (urban or rural), and the region of the country in which they lived.

As expected, the use of the advanced technologies increased over time in the entire study population. But it also increased among the men who "stood to gain the least in terms of survival."

During the 5-year study period, the use of both IMRT and robotic prostatectomy increased from 32% to 44% of men who had low-risk disease based on the clinical stage of their tumor, Gleason score, and prostate-specific antigen (PSA) level. The use of both also increased from 36% to 57% of men who were at high risk of dying from another cause. And it rose from 25% to 34% of men who had both low-risk disease and a high risk of noncancer mortality.

At the same time, the use of more conservative approaches declined to a similar degree in these low-risk patients.

In a further analysis of the data, the use of advanced treatment technologies in men who were the most unlikely to die of prostate cancer increased from 13% at the start of the 5-year period to 24% at the end, a relative increase of 85%, Dr. Jacobs and his associates said.

These trends are particularly concerning because both IMRT and robotic prostatectomy are considerably more expensive than the less aggressive approaches they are displacing, the researchers added.

Some clinicians and patients may believe that the more advanced technologies yield better outcomes, but "comparative studies have shown that the advantages of these newer treatments are marginal at best," Dr. Jacobs and his colleagues said.

"More diligence is needed to reduce the potentially unnecessary treatment of men with a low risk of dying from prostate cancer," they said.

The study was supported by the American Cancer Society, the National Institutes of Health, Blue Cross Blue Shield of Michigan, and the National Cancer Institute. Dr. Jacobs reported no financial conflicts of interest, and two of his associates reported ties to ArborMetrix and HistoSonics.

Postmenopausal hormone therapy taken at age 50-55 years produces no sustained benefit or harm to cognitive function, according to a report published online June 24 in JAMA Internal Medicine.

Women randomly assigned to receive a mean of 7 years of treatment with conjugated equine estrogens (CEEs) showed similar global cognitive function, as well as similar function in several individual cognitive domains, as those randomly assigned to receive placebo in the Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y).

A previous study of WHI participants who were at least 65 years old at enrollment showed that women given hormone therapy (HT) had small deficits in global and domain-specific cognitive functioning that persisted for years after treatment ended. Therefore, these findings concerning younger women "provide reassurance that CEE-based therapies, when administered to women earlier in the postmenopausal period, do not seem to convey long-term adverse consequences for cognitive function," said Mark A. Espeland, Ph.D., of the department of biostatistical sciences, Wake Forest University, Winston-Salem, N.C., and his associates.

However, these results also refute the "window of opportunity" hypothesis that HT might preserve or promote brain health when given just as ovarian function declines at the onset of menopause, rather than later in the process.

The WHIMS-Y study was an extension of the WHI in which 1,372 women agreed to participate in long-term follow-up after the WHI concluded. These women had been 50-55 years of age at enrollment in the WHI and had taken either HT or placebo for a mean of 7 years (range, 4-10 years) for that study.

For the WHIMS-Y study, they underwent cognitive assessment at a mean age of 68 years (range, 63-74 years).

The primary outcome was global cognitive function as measured by the Telephone Interview for Cognitive Status-modified (TICS-m). There was "essentially no difference" on this measure between women who had taken active HT and those who had taken placebo, after the data were adjusted for patient age.

In addition, no significant differences were found between the two study groups on measures of immediate and delayed verbal memory, attention, executive function, verbal fluency, and working memory, Dr. Espeland and his colleagues reported (JAMA Intern. Med. 2013 June 24 [doi: 10.1001/jamainternmed.2013.7727]).

These findings were consistent, regardless of whether the HT had been CEE alone or CEE in combination with medroxyprogesterone acetate.

Adjusting the data to account for risk factors for cognitive impairment did not alter the results. The findings also remained consistent across several subgroup analyses, with one exception: Women who had taken and then stopped HT before enrollment in the WHI and who had then resumed HT as part of the WHI showed a deficit in verbal fluency. However, this might have been a chance finding, the researchers noted.

"Although we cannot rule out acute benefits or harm, these do not appear to be present to any degree a mean of 7 years after cessation of [HT]," they said.

This study was supported by the National Institute on Aging; the WHI was funded by the National Heart, Lung, and Blood Institute. Dr. Espeland had no disclosures. One of his associates reported ties to several companies, including Amarin, Amgen, and Daiichi-Sankyo.

Postmenopausal hormone therapy taken at age 50-55 years produces no sustained benefit or harm to cognitive function, according to a report published online June 24 in JAMA Internal Medicine.

Women randomly assigned to receive a mean of 7 years of treatment with conjugated equine estrogens (CEEs) showed similar global cognitive function, as well as similar function in several individual cognitive domains, as those randomly assigned to receive placebo in the Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y).

A previous study of WHI participants who were at least 65 years old at enrollment showed that women given hormone therapy (HT) had small deficits in global and domain-specific cognitive functioning that persisted for years after treatment ended. Therefore, these findings concerning younger women "provide reassurance that CEE-based therapies, when administered to women earlier in the postmenopausal period, do not seem to convey long-term adverse consequences for cognitive function," said Mark A. Espeland, Ph.D., of the department of biostatistical sciences, Wake Forest University, Winston-Salem, N.C., and his associates.

However, these results also refute the "window of opportunity" hypothesis that HT might preserve or promote brain health when given just as ovarian function declines at the onset of menopause, rather than later in the process.

The WHIMS-Y study was an extension of the WHI in which 1,372 women agreed to participate in long-term follow-up after the WHI concluded. These women had been 50-55 years of age at enrollment in the WHI and had taken either HT or placebo for a mean of 7 years (range, 4-10 years) for that study.

For the WHIMS-Y study, they underwent cognitive assessment at a mean age of 68 years (range, 63-74 years).

The primary outcome was global cognitive function as measured by the Telephone Interview for Cognitive Status-modified (TICS-m). There was "essentially no difference" on this measure between women who had taken active HT and those who had taken placebo, after the data were adjusted for patient age.

In addition, no significant differences were found between the two study groups on measures of immediate and delayed verbal memory, attention, executive function, verbal fluency, and working memory, Dr. Espeland and his colleagues reported (JAMA Intern. Med. 2013 June 24 [doi: 10.1001/jamainternmed.2013.7727]).

These findings were consistent, regardless of whether the HT had been CEE alone or CEE in combination with medroxyprogesterone acetate.

Adjusting the data to account for risk factors for cognitive impairment did not alter the results. The findings also remained consistent across several subgroup analyses, with one exception: Women who had taken and then stopped HT before enrollment in the WHI and who had then resumed HT as part of the WHI showed a deficit in verbal fluency. However, this might have been a chance finding, the researchers noted.

"Although we cannot rule out acute benefits or harm, these do not appear to be present to any degree a mean of 7 years after cessation of [HT]," they said.

This study was supported by the National Institute on Aging; the WHI was funded by the National Heart, Lung, and Blood Institute. Dr. Espeland had no disclosures. One of his associates reported ties to several companies, including Amarin, Amgen, and Daiichi-Sankyo.

Postmenopausal hormone therapy taken at age 50-55 years produces no sustained benefit or harm to cognitive function, according to a report published online June 24 in JAMA Internal Medicine.

Women randomly assigned to receive a mean of 7 years of treatment with conjugated equine estrogens (CEEs) showed similar global cognitive function, as well as similar function in several individual cognitive domains, as those randomly assigned to receive placebo in the Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y).

A previous study of WHI participants who were at least 65 years old at enrollment showed that women given hormone therapy (HT) had small deficits in global and domain-specific cognitive functioning that persisted for years after treatment ended. Therefore, these findings concerning younger women "provide reassurance that CEE-based therapies, when administered to women earlier in the postmenopausal period, do not seem to convey long-term adverse consequences for cognitive function," said Mark A. Espeland, Ph.D., of the department of biostatistical sciences, Wake Forest University, Winston-Salem, N.C., and his associates.

However, these results also refute the "window of opportunity" hypothesis that HT might preserve or promote brain health when given just as ovarian function declines at the onset of menopause, rather than later in the process.

The WHIMS-Y study was an extension of the WHI in which 1,372 women agreed to participate in long-term follow-up after the WHI concluded. These women had been 50-55 years of age at enrollment in the WHI and had taken either HT or placebo for a mean of 7 years (range, 4-10 years) for that study.

For the WHIMS-Y study, they underwent cognitive assessment at a mean age of 68 years (range, 63-74 years).

The primary outcome was global cognitive function as measured by the Telephone Interview for Cognitive Status-modified (TICS-m). There was "essentially no difference" on this measure between women who had taken active HT and those who had taken placebo, after the data were adjusted for patient age.

In addition, no significant differences were found between the two study groups on measures of immediate and delayed verbal memory, attention, executive function, verbal fluency, and working memory, Dr. Espeland and his colleagues reported (JAMA Intern. Med. 2013 June 24 [doi: 10.1001/jamainternmed.2013.7727]).

These findings were consistent, regardless of whether the HT had been CEE alone or CEE in combination with medroxyprogesterone acetate.

Adjusting the data to account for risk factors for cognitive impairment did not alter the results. The findings also remained consistent across several subgroup analyses, with one exception: Women who had taken and then stopped HT before enrollment in the WHI and who had then resumed HT as part of the WHI showed a deficit in verbal fluency. However, this might have been a chance finding, the researchers noted.

"Although we cannot rule out acute benefits or harm, these do not appear to be present to any degree a mean of 7 years after cessation of [HT]," they said.

This study was supported by the National Institute on Aging; the WHI was funded by the National Heart, Lung, and Blood Institute. Dr. Espeland had no disclosures. One of his associates reported ties to several companies, including Amarin, Amgen, and Daiichi-Sankyo.

A study that tracked the incidence of Guillain-Barré syndrome in Californians over the course of more than 30 million person-years found no evidence that risk that immunization increased the risk for the disorder, according to a report published online in Clinical Infectious Diseases.

This retrospective study could not definitively exclude a possible weak association between vaccines and GBS, partly because the rarity of the disorder limited the study’s power to fully assess this risk. But the findings "provide reassurance that the risk of GBS following any vaccine ... is extremely low," said Dr. Roger Baxter of the Kaiser Permanente Vaccine Study Center, Oakland, Calif., and his associates.

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Concern about a link between vaccinations and GBS have "flourished" since a study found a small but significant increase in cases during the 6 weeks following immunization against the 1976 Swine flu. Since that time, studies assessing GBS risk after seasonal flu vaccinations "have shown either no risk or a very small attributable risk of approximately one case per million doses," the investigators wrote (Clin. Infect. Dis. 2013;57:197-204 [doi:10.1093/cid/cit222]).

Similarly, no conclusive evidence has been found linking GBS with other vaccines, but there have been a small number of case reports in which the disorder developed following tetanus, rabies, polio, or hepatitis B vaccination.

In contrast, the evidence is clear that GBS is temporally associated with infectious diseases. "Most published case series report that approximately two-thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior 3 months. Campylobacter enteritis is the most common trigger, but influenza, cytomegalovirus, Epstein Barr virus, HIV, and Mycoplasma pneumoniae, among others, have been implicated as well," Dr. Baxter and his colleagues said.

They used information from Kaiser’s database of electronic medical records and its immunization tracking system to examine a possible association between GBS and immunizations. The researchers identified 415 patients who were hospitalized with GBS between 1994 and 2006 and had received any vaccination during the year preceding symptom onset.

During 32,734,642 person-years of observation, the overall incidence was 1.27 cases of GBS/100,000 person-years. This rate is comparable with that reported in previous studies of GBS incidence.

As has been reported in previous studies, the majority (59%) of cases in this study occurred in males.

The mean age of GBS patients was 49 years (range, 5-87 years). Two-thirds of cases (67%) had a documented respiratory or gastrointestinal illness during the 90 days preceding onset of GBS.

Only 25 of these 415 patients had received any vaccine during the 6 weeks before symptom onset. This included 18 patients who had received influenza vaccines, and one to three patients each of whom had received vaccines against pneumococcus, tetanus-diphtheria, hepatitis A, or hepatitis B, Dr. Baxter and his associates said.

Of the 18 patients who developed GBS within 6 weeks of receiving an influenza vaccine, 13 had known respiratory or gastrointestinal illness during that period, which also may have predisposed them to GBS. These 18 cases also occurred against a backdrop of 6,841,901 flu immunizations given during that interval.

Six of the remaining seven patients who developed GBS within 6 weeks of a noninfluenza vaccination also had respiratory or gastrointestinal illness during that interval.

There was no association between GBS and any of the vaccines typically administered during childhood, despite the extremely large number of doses given: For example, 1.2 million doses of oral polio vaccine, 1.6 million of MMR, and 764,000 varicella vaccine were dispensed.

There was no significant difference in the rate of GBS among people vaccinated up to 6 weeks prior to symptom onset and those vaccinated from 6 weeks to 12 months prior to symptom onset, judging from the findings of a secondary cohort analysis.

GBS was significantly more likely to occur during the winter months than during any other season.

This study was supported by America\'s Health Insurance Plans and the Centers for Disease Control and Prevention. Dr. Baxter and one of his associates reported ties to GlaxoSmithKline, MedImmune, Merck, Novartis Vaccines, Pfizer, and Sanofi-Pasteur.

A study that tracked the incidence of Guillain-Barré syndrome in Californians over the course of more than 30 million person-years found no evidence that risk that immunization increased the risk for the disorder, according to a report published online in Clinical Infectious Diseases.

This retrospective study could not definitively exclude a possible weak association between vaccines and GBS, partly because the rarity of the disorder limited the study’s power to fully assess this risk. But the findings "provide reassurance that the risk of GBS following any vaccine ... is extremely low," said Dr. Roger Baxter of the Kaiser Permanente Vaccine Study Center, Oakland, Calif., and his associates.

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Concern about a link between vaccinations and GBS have "flourished" since a study found a small but significant increase in cases during the 6 weeks following immunization against the 1976 Swine flu. Since that time, studies assessing GBS risk after seasonal flu vaccinations "have shown either no risk or a very small attributable risk of approximately one case per million doses," the investigators wrote (Clin. Infect. Dis. 2013;57:197-204 [doi:10.1093/cid/cit222]).

Similarly, no conclusive evidence has been found linking GBS with other vaccines, but there have been a small number of case reports in which the disorder developed following tetanus, rabies, polio, or hepatitis B vaccination.

In contrast, the evidence is clear that GBS is temporally associated with infectious diseases. "Most published case series report that approximately two-thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior 3 months. Campylobacter enteritis is the most common trigger, but influenza, cytomegalovirus, Epstein Barr virus, HIV, and Mycoplasma pneumoniae, among others, have been implicated as well," Dr. Baxter and his colleagues said.

They used information from Kaiser’s database of electronic medical records and its immunization tracking system to examine a possible association between GBS and immunizations. The researchers identified 415 patients who were hospitalized with GBS between 1994 and 2006 and had received any vaccination during the year preceding symptom onset.

During 32,734,642 person-years of observation, the overall incidence was 1.27 cases of GBS/100,000 person-years. This rate is comparable with that reported in previous studies of GBS incidence.

As has been reported in previous studies, the majority (59%) of cases in this study occurred in males.

The mean age of GBS patients was 49 years (range, 5-87 years). Two-thirds of cases (67%) had a documented respiratory or gastrointestinal illness during the 90 days preceding onset of GBS.

Only 25 of these 415 patients had received any vaccine during the 6 weeks before symptom onset. This included 18 patients who had received influenza vaccines, and one to three patients each of whom had received vaccines against pneumococcus, tetanus-diphtheria, hepatitis A, or hepatitis B, Dr. Baxter and his associates said.

Of the 18 patients who developed GBS within 6 weeks of receiving an influenza vaccine, 13 had known respiratory or gastrointestinal illness during that period, which also may have predisposed them to GBS. These 18 cases also occurred against a backdrop of 6,841,901 flu immunizations given during that interval.

Six of the remaining seven patients who developed GBS within 6 weeks of a noninfluenza vaccination also had respiratory or gastrointestinal illness during that interval.

There was no association between GBS and any of the vaccines typically administered during childhood, despite the extremely large number of doses given: For example, 1.2 million doses of oral polio vaccine, 1.6 million of MMR, and 764,000 varicella vaccine were dispensed.

There was no significant difference in the rate of GBS among people vaccinated up to 6 weeks prior to symptom onset and those vaccinated from 6 weeks to 12 months prior to symptom onset, judging from the findings of a secondary cohort analysis.

GBS was significantly more likely to occur during the winter months than during any other season.

This study was supported by America\'s Health Insurance Plans and the Centers for Disease Control and Prevention. Dr. Baxter and one of his associates reported ties to GlaxoSmithKline, MedImmune, Merck, Novartis Vaccines, Pfizer, and Sanofi-Pasteur.

A study that tracked the incidence of Guillain-Barré syndrome in Californians over the course of more than 30 million person-years found no evidence that risk that immunization increased the risk for the disorder, according to a report published online in Clinical Infectious Diseases.

This retrospective study could not definitively exclude a possible weak association between vaccines and GBS, partly because the rarity of the disorder limited the study’s power to fully assess this risk. But the findings "provide reassurance that the risk of GBS following any vaccine ... is extremely low," said Dr. Roger Baxter of the Kaiser Permanente Vaccine Study Center, Oakland, Calif., and his associates.

DesignPics.com

Concern about a link between vaccinations and GBS have "flourished" since a study found a small but significant increase in cases during the 6 weeks following immunization against the 1976 Swine flu. Since that time, studies assessing GBS risk after seasonal flu vaccinations "have shown either no risk or a very small attributable risk of approximately one case per million doses," the investigators wrote (Clin. Infect. Dis. 2013;57:197-204 [doi:10.1093/cid/cit222]).

Similarly, no conclusive evidence has been found linking GBS with other vaccines, but there have been a small number of case reports in which the disorder developed following tetanus, rabies, polio, or hepatitis B vaccination.

In contrast, the evidence is clear that GBS is temporally associated with infectious diseases. "Most published case series report that approximately two-thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior 3 months. Campylobacter enteritis is the most common trigger, but influenza, cytomegalovirus, Epstein Barr virus, HIV, and Mycoplasma pneumoniae, among others, have been implicated as well," Dr. Baxter and his colleagues said.

They used information from Kaiser’s database of electronic medical records and its immunization tracking system to examine a possible association between GBS and immunizations. The researchers identified 415 patients who were hospitalized with GBS between 1994 and 2006 and had received any vaccination during the year preceding symptom onset.

During 32,734,642 person-years of observation, the overall incidence was 1.27 cases of GBS/100,000 person-years. This rate is comparable with that reported in previous studies of GBS incidence.

As has been reported in previous studies, the majority (59%) of cases in this study occurred in males.

The mean age of GBS patients was 49 years (range, 5-87 years). Two-thirds of cases (67%) had a documented respiratory or gastrointestinal illness during the 90 days preceding onset of GBS.

Only 25 of these 415 patients had received any vaccine during the 6 weeks before symptom onset. This included 18 patients who had received influenza vaccines, and one to three patients each of whom had received vaccines against pneumococcus, tetanus-diphtheria, hepatitis A, or hepatitis B, Dr. Baxter and his associates said.

Of the 18 patients who developed GBS within 6 weeks of receiving an influenza vaccine, 13 had known respiratory or gastrointestinal illness during that period, which also may have predisposed them to GBS. These 18 cases also occurred against a backdrop of 6,841,901 flu immunizations given during that interval.

Six of the remaining seven patients who developed GBS within 6 weeks of a noninfluenza vaccination also had respiratory or gastrointestinal illness during that interval.

There was no association between GBS and any of the vaccines typically administered during childhood, despite the extremely large number of doses given: For example, 1.2 million doses of oral polio vaccine, 1.6 million of MMR, and 764,000 varicella vaccine were dispensed.

There was no significant difference in the rate of GBS among people vaccinated up to 6 weeks prior to symptom onset and those vaccinated from 6 weeks to 12 months prior to symptom onset, judging from the findings of a secondary cohort analysis.

GBS was significantly more likely to occur during the winter months than during any other season.

This study was supported by America\'s Health Insurance Plans and the Centers for Disease Control and Prevention. Dr. Baxter and one of his associates reported ties to GlaxoSmithKline, MedImmune, Merck, Novartis Vaccines, Pfizer, and Sanofi-Pasteur.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

In children at genetic risk for type 1 diabetes, the development of multiple circulating islet autoantibodies predicts progression to the disease, usually within a few years, according to a pooled analysisreported in the June 19 issue of JAMA.

This means that at-risk children enter a preclinical stage of type 1 diabetes when they seroconvert, said Dr. Anette G. Ziegler of the Institute of Diabetes Research and Technische Universität Munchen, Neuherberg (Germany), and her associates.

The interval between seroconversion and progression to full-blown type 1 diabetes varies widely, from a few weeks to many years, depending on a variety of factors.

"Our findings highlight the need for research into finding interventions to stop the development of multiple islet autoantibodies and to stop or delay progression to type 1 diabetes. Children with islet autoantibodies who do not develop diabetes for more than 15 years and the factors associated with slower progression ... should also be studied, because it may be helpful for understanding natural protective mechanisms," the investigators wrote.

Dr. Ziegler and her colleagues noted that islet autoantibody seroconversion is relatively common during the first years of life in at-risk children, but information on diabetes progression is limited. They pooled the data from three large, long-term studies to examine the issue.

The Colorado Diabetes Autoimmunity Study in the Young (DAISY), the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study, and the German combined BABYDIAB and BABYDIET studies all investigated the natural history of autoimmunity in children at risk for diabetes, following their study subjects from birth to as old as 18 years.

All three studies frequently tested the subjects’ blood samples for autoantibodies against insulin, glutamic acid decarboxylase (GAD65), and insulinoma antigen 2 (IA2) to track the age at which seroconversion took place. There were 13,377 children in the pooled analysis: 1,962 in Colorado, 8,597 in Finland, and 2,818 in Germany.

A total of 1,059 children, 8% of the entire study population, seroconverted to islet-autoantibody positivity, while 12,318 (92%) did not seroconvert. Of those who did seroconvert, slightly more than half developed positivity to multiple autoantibodies. The median age at seroconversion to multiple islet autoantibodies was 2 years.

A total of 482 study subjects developed type 1 diabetes during follow-up. Only 25 of these progressed to diabetes before showing seroconversion.

The risk of developing diabetes by the age of 15 years was 79% in children who carried all three islet autoantibodies, 62% in those who carried two islet autoantibodies, and 13% in those who carried a single islet autoantibody. In contrast, the risk was only 0.4% in children who had no islet autoantibodies.

Children who seroconverted with multiple islet autoantibodies developed diabetes a median of 3.5 years later, at a median age of 6 years.

Progression to diabetes after seroconversion was 44% at 5-year follow-up, 69% at 10-year follow-up, and 84% at 15-year follow-up, Dr. Ziegler and her associates said (JAMA 2013;309:2473-9).

The interval between seroconversion and progression to diabetes varied from a few weeks to 18 years. Faster progression to diabetes after seroconversion was associated with younger age (less than 3 years) at seroconversion, the human leukocyte antigen (HLA) DR3/DR4-DQ8 genotype, and female sex.

This study was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft. Dr. Ziegler reported no relevant financial conflicts of interest; one of her associates reported ties to Novo Nordisk Diabetes and Medtronic Nordic.

In children at genetic risk for type 1 diabetes, the development of multiple circulating islet autoantibodies predicts progression to the disease, usually within a few years, according to a pooled analysisreported in the June 19 issue of JAMA.

This means that at-risk children enter a preclinical stage of type 1 diabetes when they seroconvert, said Dr. Anette G. Ziegler of the Institute of Diabetes Research and Technische Universität Munchen, Neuherberg (Germany), and her associates.

The interval between seroconversion and progression to full-blown type 1 diabetes varies widely, from a few weeks to many years, depending on a variety of factors.

"Our findings highlight the need for research into finding interventions to stop the development of multiple islet autoantibodies and to stop or delay progression to type 1 diabetes. Children with islet autoantibodies who do not develop diabetes for more than 15 years and the factors associated with slower progression ... should also be studied, because it may be helpful for understanding natural protective mechanisms," the investigators wrote.

Dr. Ziegler and her colleagues noted that islet autoantibody seroconversion is relatively common during the first years of life in at-risk children, but information on diabetes progression is limited. They pooled the data from three large, long-term studies to examine the issue.

The Colorado Diabetes Autoimmunity Study in the Young (DAISY), the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study, and the German combined BABYDIAB and BABYDIET studies all investigated the natural history of autoimmunity in children at risk for diabetes, following their study subjects from birth to as old as 18 years.

All three studies frequently tested the subjects’ blood samples for autoantibodies against insulin, glutamic acid decarboxylase (GAD65), and insulinoma antigen 2 (IA2) to track the age at which seroconversion took place. There were 13,377 children in the pooled analysis: 1,962 in Colorado, 8,597 in Finland, and 2,818 in Germany.

A total of 1,059 children, 8% of the entire study population, seroconverted to islet-autoantibody positivity, while 12,318 (92%) did not seroconvert. Of those who did seroconvert, slightly more than half developed positivity to multiple autoantibodies. The median age at seroconversion to multiple islet autoantibodies was 2 years.

A total of 482 study subjects developed type 1 diabetes during follow-up. Only 25 of these progressed to diabetes before showing seroconversion.

The risk of developing diabetes by the age of 15 years was 79% in children who carried all three islet autoantibodies, 62% in those who carried two islet autoantibodies, and 13% in those who carried a single islet autoantibody. In contrast, the risk was only 0.4% in children who had no islet autoantibodies.

Children who seroconverted with multiple islet autoantibodies developed diabetes a median of 3.5 years later, at a median age of 6 years.

Progression to diabetes after seroconversion was 44% at 5-year follow-up, 69% at 10-year follow-up, and 84% at 15-year follow-up, Dr. Ziegler and her associates said (JAMA 2013;309:2473-9).

The interval between seroconversion and progression to diabetes varied from a few weeks to 18 years. Faster progression to diabetes after seroconversion was associated with younger age (less than 3 years) at seroconversion, the human leukocyte antigen (HLA) DR3/DR4-DQ8 genotype, and female sex.

This study was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft. Dr. Ziegler reported no relevant financial conflicts of interest; one of her associates reported ties to Novo Nordisk Diabetes and Medtronic Nordic.

In children at genetic risk for type 1 diabetes, the development of multiple circulating islet autoantibodies predicts progression to the disease, usually within a few years, according to a pooled analysisreported in the June 19 issue of JAMA.

This means that at-risk children enter a preclinical stage of type 1 diabetes when they seroconvert, said Dr. Anette G. Ziegler of the Institute of Diabetes Research and Technische Universität Munchen, Neuherberg (Germany), and her associates.

The interval between seroconversion and progression to full-blown type 1 diabetes varies widely, from a few weeks to many years, depending on a variety of factors.

"Our findings highlight the need for research into finding interventions to stop the development of multiple islet autoantibodies and to stop or delay progression to type 1 diabetes. Children with islet autoantibodies who do not develop diabetes for more than 15 years and the factors associated with slower progression ... should also be studied, because it may be helpful for understanding natural protective mechanisms," the investigators wrote.

Dr. Ziegler and her colleagues noted that islet autoantibody seroconversion is relatively common during the first years of life in at-risk children, but information on diabetes progression is limited. They pooled the data from three large, long-term studies to examine the issue.

The Colorado Diabetes Autoimmunity Study in the Young (DAISY), the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study, and the German combined BABYDIAB and BABYDIET studies all investigated the natural history of autoimmunity in children at risk for diabetes, following their study subjects from birth to as old as 18 years.

All three studies frequently tested the subjects’ blood samples for autoantibodies against insulin, glutamic acid decarboxylase (GAD65), and insulinoma antigen 2 (IA2) to track the age at which seroconversion took place. There were 13,377 children in the pooled analysis: 1,962 in Colorado, 8,597 in Finland, and 2,818 in Germany.

A total of 1,059 children, 8% of the entire study population, seroconverted to islet-autoantibody positivity, while 12,318 (92%) did not seroconvert. Of those who did seroconvert, slightly more than half developed positivity to multiple autoantibodies. The median age at seroconversion to multiple islet autoantibodies was 2 years.

A total of 482 study subjects developed type 1 diabetes during follow-up. Only 25 of these progressed to diabetes before showing seroconversion.

The risk of developing diabetes by the age of 15 years was 79% in children who carried all three islet autoantibodies, 62% in those who carried two islet autoantibodies, and 13% in those who carried a single islet autoantibody. In contrast, the risk was only 0.4% in children who had no islet autoantibodies.

Children who seroconverted with multiple islet autoantibodies developed diabetes a median of 3.5 years later, at a median age of 6 years.

Progression to diabetes after seroconversion was 44% at 5-year follow-up, 69% at 10-year follow-up, and 84% at 15-year follow-up, Dr. Ziegler and her associates said (JAMA 2013;309:2473-9).

The interval between seroconversion and progression to diabetes varied from a few weeks to 18 years. Faster progression to diabetes after seroconversion was associated with younger age (less than 3 years) at seroconversion, the human leukocyte antigen (HLA) DR3/DR4-DQ8 genotype, and female sex.

This study was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft. Dr. Ziegler reported no relevant financial conflicts of interest; one of her associates reported ties to Novo Nordisk Diabetes and Medtronic Nordic.

Every 15-minute increment of time saved until patients with acute ischemic stroke receive tissue plasminogen activator was associated with fewer deaths and greater numbers of patients discharged with improved ambulation or to their home in the largest study to date of real-world experience with TPA.

The report, which used patients with longer intervals between symptom onset and TPA administration as a reference group, also showed that patients who received TPA earlier had fewer symptomatic intracranial hemorrhages, Dr. Jeffrey L. Saver and his associates reported. The report was published June 19 in JAMA. Dr. Saver is director of the stroke and vascular neurology clinic at the University of California, Los Angeles.

Given 1,000 treated patients, every 15-minute increment of time saved until administration of TPA was associated with 4 fewer in-hospital deaths, 18 more patients having improved ambulation at discharge, and 13 more patients being discharged to an independent environment, the investigators noted (JAMA 2013;309:2480-8).

These findings confirm and extend the results of several formal but small clinical trials of TPA. With a study population more than 30 times larger than that of all patients who took part in TPA clinical trials, the results of this study demonstrate a much greater magnitude of benefit than previous studies were able to do.

Until now, it was not certain that the benefits of early TPA administration shown in clinical trials would generalize to more diverse patients and hospitals in real-world practice, Dr. Saver and his colleagues said.

"The findings from this study emphasize the importance of worldwide efforts to shorten onset to lytic treatment times for acute ischemic stroke," they wrote.

The investigators used data in the Get With The Guidelines–Stroke registry of the American Heart Association and the American Stroke Association, which collects information on consecutive stroke and transient ischemic attack (TIA) patients admitted to hospital emergency departments across the country. They focused on 58,353 patients admitted to 1,395 participating sites during a 10-year period who received IV TPA within the 4.5 hours of symptom onset recommended in current national guidelines.

Median patient age was 72 years. The study population was equally divided between men and women. The mean interval between symptom onset and administration of TPA was 144 minutes.

A total of 5,404 patients (9.3% of the study population) received TPA within 90 minutes, while 45,029 (77.2%) received it at 91-180 minutes, and 7,920 (13.5%) received it at 181-270 minutes.

Overall, there were 5,142 (8.8%) in-hospital deaths. A total of 2,873 patients (4.9%) had intracranial hemorrhage, 22,541 (38.6%) were discharged home, and 19,491 (33.4%) were able to walk independently at discharge.

Faster TPA administration was associated with several positive outcomes. For every 15-minute-faster interval before treatment, mortality was less likely to occur (odds ratio = 0.96), symptomatic intracranial hemorrhage was less likely to occur (OR = 0.96; 95% confidence interval, 0.95-0.98), independent ambulation was more likely to occur (OR = 1.04; 95% CI, 1.03-1.05), and discharge home rather than to a care facility was more likely to occur (OR = 1.03; 95% CI, 1.02-1.04), Dr. Saver and his colleagues said.

These associations remained robust in several further analyses of the data. They also remained consistent across subgroups of patients regardless of age, sex, race/ethnicity, and the severity of stroke at presentation.

"These findings support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care" so as to shorten the interval between symptom onset and TPA administration, the investigators added.

The Get With The Guidelines–Stroke program of the American Heart Association and the American Stroke Association is supported in part by Janssen Pharmaceuticals. Dr. Saver reported ties to Covidien, CoAxia, Grifols, Brainsgate, Lundbeck, and St. Jude Medical; his associates reported ties to numerous industry sources.

Every 15-minute increment of time saved until patients with acute ischemic stroke receive tissue plasminogen activator was associated with fewer deaths and greater numbers of patients discharged with improved ambulation or to their home in the largest study to date of real-world experience with TPA.

The report, which used patients with longer intervals between symptom onset and TPA administration as a reference group, also showed that patients who received TPA earlier had fewer symptomatic intracranial hemorrhages, Dr. Jeffrey L. Saver and his associates reported. The report was published June 19 in JAMA. Dr. Saver is director of the stroke and vascular neurology clinic at the University of California, Los Angeles.

Given 1,000 treated patients, every 15-minute increment of time saved until administration of TPA was associated with 4 fewer in-hospital deaths, 18 more patients having improved ambulation at discharge, and 13 more patients being discharged to an independent environment, the investigators noted (JAMA 2013;309:2480-8).

These findings confirm and extend the results of several formal but small clinical trials of TPA. With a study population more than 30 times larger than that of all patients who took part in TPA clinical trials, the results of this study demonstrate a much greater magnitude of benefit than previous studies were able to do.

Until now, it was not certain that the benefits of early TPA administration shown in clinical trials would generalize to more diverse patients and hospitals in real-world practice, Dr. Saver and his colleagues said.

"The findings from this study emphasize the importance of worldwide efforts to shorten onset to lytic treatment times for acute ischemic stroke," they wrote.

The investigators used data in the Get With The Guidelines–Stroke registry of the American Heart Association and the American Stroke Association, which collects information on consecutive stroke and transient ischemic attack (TIA) patients admitted to hospital emergency departments across the country. They focused on 58,353 patients admitted to 1,395 participating sites during a 10-year period who received IV TPA within the 4.5 hours of symptom onset recommended in current national guidelines.

Median patient age was 72 years. The study population was equally divided between men and women. The mean interval between symptom onset and administration of TPA was 144 minutes.

A total of 5,404 patients (9.3% of the study population) received TPA within 90 minutes, while 45,029 (77.2%) received it at 91-180 minutes, and 7,920 (13.5%) received it at 181-270 minutes.

Overall, there were 5,142 (8.8%) in-hospital deaths. A total of 2,873 patients (4.9%) had intracranial hemorrhage, 22,541 (38.6%) were discharged home, and 19,491 (33.4%) were able to walk independently at discharge.

Faster TPA administration was associated with several positive outcomes. For every 15-minute-faster interval before treatment, mortality was less likely to occur (odds ratio = 0.96), symptomatic intracranial hemorrhage was less likely to occur (OR = 0.96; 95% confidence interval, 0.95-0.98), independent ambulation was more likely to occur (OR = 1.04; 95% CI, 1.03-1.05), and discharge home rather than to a care facility was more likely to occur (OR = 1.03; 95% CI, 1.02-1.04), Dr. Saver and his colleagues said.

These associations remained robust in several further analyses of the data. They also remained consistent across subgroups of patients regardless of age, sex, race/ethnicity, and the severity of stroke at presentation.

"These findings support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care" so as to shorten the interval between symptom onset and TPA administration, the investigators added.

The Get With The Guidelines–Stroke program of the American Heart Association and the American Stroke Association is supported in part by Janssen Pharmaceuticals. Dr. Saver reported ties to Covidien, CoAxia, Grifols, Brainsgate, Lundbeck, and St. Jude Medical; his associates reported ties to numerous industry sources.

Every 15-minute increment of time saved until patients with acute ischemic stroke receive tissue plasminogen activator was associated with fewer deaths and greater numbers of patients discharged with improved ambulation or to their home in the largest study to date of real-world experience with TPA.

The report, which used patients with longer intervals between symptom onset and TPA administration as a reference group, also showed that patients who received TPA earlier had fewer symptomatic intracranial hemorrhages, Dr. Jeffrey L. Saver and his associates reported. The report was published June 19 in JAMA. Dr. Saver is director of the stroke and vascular neurology clinic at the University of California, Los Angeles.

Given 1,000 treated patients, every 15-minute increment of time saved until administration of TPA was associated with 4 fewer in-hospital deaths, 18 more patients having improved ambulation at discharge, and 13 more patients being discharged to an independent environment, the investigators noted (JAMA 2013;309:2480-8).

These findings confirm and extend the results of several formal but small clinical trials of TPA. With a study population more than 30 times larger than that of all patients who took part in TPA clinical trials, the results of this study demonstrate a much greater magnitude of benefit than previous studies were able to do.

Until now, it was not certain that the benefits of early TPA administration shown in clinical trials would generalize to more diverse patients and hospitals in real-world practice, Dr. Saver and his colleagues said.

"The findings from this study emphasize the importance of worldwide efforts to shorten onset to lytic treatment times for acute ischemic stroke," they wrote.

The investigators used data in the Get With The Guidelines–Stroke registry of the American Heart Association and the American Stroke Association, which collects information on consecutive stroke and transient ischemic attack (TIA) patients admitted to hospital emergency departments across the country. They focused on 58,353 patients admitted to 1,395 participating sites during a 10-year period who received IV TPA within the 4.5 hours of symptom onset recommended in current national guidelines.

Median patient age was 72 years. The study population was equally divided between men and women. The mean interval between symptom onset and administration of TPA was 144 minutes.

A total of 5,404 patients (9.3% of the study population) received TPA within 90 minutes, while 45,029 (77.2%) received it at 91-180 minutes, and 7,920 (13.5%) received it at 181-270 minutes.

Overall, there were 5,142 (8.8%) in-hospital deaths. A total of 2,873 patients (4.9%) had intracranial hemorrhage, 22,541 (38.6%) were discharged home, and 19,491 (33.4%) were able to walk independently at discharge.

Faster TPA administration was associated with several positive outcomes. For every 15-minute-faster interval before treatment, mortality was less likely to occur (odds ratio = 0.96), symptomatic intracranial hemorrhage was less likely to occur (OR = 0.96; 95% confidence interval, 0.95-0.98), independent ambulation was more likely to occur (OR = 1.04; 95% CI, 1.03-1.05), and discharge home rather than to a care facility was more likely to occur (OR = 1.03; 95% CI, 1.02-1.04), Dr. Saver and his colleagues said.

These associations remained robust in several further analyses of the data. They also remained consistent across subgroups of patients regardless of age, sex, race/ethnicity, and the severity of stroke at presentation.

"These findings support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care" so as to shorten the interval between symptom onset and TPA administration, the investigators added.

The Get With The Guidelines–Stroke program of the American Heart Association and the American Stroke Association is supported in part by Janssen Pharmaceuticals. Dr. Saver reported ties to Covidien, CoAxia, Grifols, Brainsgate, Lundbeck, and St. Jude Medical; his associates reported ties to numerous industry sources.

Increased consumption of red meat over a 4-year period was associated with higher risk that type 2 diabetes would develop during the next 4 years, according to a report published online June 17 in JAMA Internal Medicine.

This association was strong in both men and women in a large cohort study with 12-16 years of follow-up, regardless of the subjects’ baseline level of red meat intake, the overall quality of their diet, or their body weight, said An Pan, Ph.D., of the department of nutrition, Harvard School of Public Health, Boston, and his associates.

Previous studies, largely cross-sectional, have noted a correlation between the consumption of red meat and current diabetes risk but have had limited duration of follow-up. This is the first study to assess changes in the intake of red meat over time and subsequent diabetes risk, and it confirms the robustness of the association, the investigators said.

©Len Rizzi/National Cancer Institute

However, because this was an observational study, it cannot determine causality, they noted.

Dr. Pan and his colleagues examined the issue using data from three large cohort studies: the Health Professionals Follow-Up Study (HPFS), the Nurses’ Health Study (NHS), and the Nurses’ Health Study II (NHS II). All of these collected measurements of red meat intake every 4 years, as well as other dietary, lifestyle, and medical factors.

For their investigation, Dr. Pan and his associates analyzed data for 26,357 male health care professionals aged 40-75 years at baseline in 1986 and 122,786 female nurses aged 25-55 years at baseline in either 1986 or 1991.

These subjects reported how often, on average, they consumed a standard portion size of red meat, which was defined as beef, pork, or lamb as a main dish; hamburger; beef, pork or lamb as a sandwich or mixed dish; as well as bacon, hot dogs, sausage, salami, bologna, and other processed red meats. The responses ranged from never or less than once per month to six or more times per day.

A total of 7,540 cases of incident type 2 diabetes developed during follow-up: 1,561 in the HPFS, 3,482 in the NHS, and 2,497 in the NHS II.

Compared with people whose intake of red meat was relatively stable during each 4-year period, those who increased their intake were at elevated risk for developing diabetes in all three cohorts, said Dr. Pan, who is also at the National University of Singapore, and his colleagues.

Raising consumption by more than 0.5 servings per day was associated with a 48% rise in diabetes risk during the next 4 years in the study population as a whole. And even among nonobese adults, increasing intake by 0.5 servings per day was associated with a 65% greater risk of diabetes, the investigators said (JAMA Intern. Med. 2013 June 17 [doi:10.1001/jamainternmed.2013.6633]).

Diabetes risk was "modestly" attenuated when the data were adjusted to account for the concurrent weight gain that often accompanied greater intake of red meat. This suggests that weight gain accounted for some, but not all, of the association between red meat intake and diabetes.

In addition, the association was stronger for processed than for nonprocessed red meats.

Unfortunately, study subjects who cut back on red meat did not show a significant reduction in diabetes risk during the ensuing 4 years. However, the highest reduction of red meat intake – decreasing consumption by more than 0.5 servings per day during the initial 4 years of follow-up – was associated with a 10% lower risk of diabetes by the end of the entire follow-up of 16 years after adjustment for BMI plus concurrent weight gain.

This study was limited in that the reasons why subjects increased or decreased their intake of red meat were unknown, and could not be accounted for in the data analysis. In addition, the study subjects were primarily white and well-educated adults, so the findings may not be generalizable to other populations, the researchers said.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Increased consumption of red meat over a 4-year period was associated with higher risk that type 2 diabetes would develop during the next 4 years, according to a report published online June 17 in JAMA Internal Medicine.

This association was strong in both men and women in a large cohort study with 12-16 years of follow-up, regardless of the subjects’ baseline level of red meat intake, the overall quality of their diet, or their body weight, said An Pan, Ph.D., of the department of nutrition, Harvard School of Public Health, Boston, and his associates.

Previous studies, largely cross-sectional, have noted a correlation between the consumption of red meat and current diabetes risk but have had limited duration of follow-up. This is the first study to assess changes in the intake of red meat over time and subsequent diabetes risk, and it confirms the robustness of the association, the investigators said.

©Len Rizzi/National Cancer Institute

However, because this was an observational study, it cannot determine causality, they noted.

Dr. Pan and his colleagues examined the issue using data from three large cohort studies: the Health Professionals Follow-Up Study (HPFS), the Nurses’ Health Study (NHS), and the Nurses’ Health Study II (NHS II). All of these collected measurements of red meat intake every 4 years, as well as other dietary, lifestyle, and medical factors.

For their investigation, Dr. Pan and his associates analyzed data for 26,357 male health care professionals aged 40-75 years at baseline in 1986 and 122,786 female nurses aged 25-55 years at baseline in either 1986 or 1991.

These subjects reported how often, on average, they consumed a standard portion size of red meat, which was defined as beef, pork, or lamb as a main dish; hamburger; beef, pork or lamb as a sandwich or mixed dish; as well as bacon, hot dogs, sausage, salami, bologna, and other processed red meats. The responses ranged from never or less than once per month to six or more times per day.

A total of 7,540 cases of incident type 2 diabetes developed during follow-up: 1,561 in the HPFS, 3,482 in the NHS, and 2,497 in the NHS II.

Compared with people whose intake of red meat was relatively stable during each 4-year period, those who increased their intake were at elevated risk for developing diabetes in all three cohorts, said Dr. Pan, who is also at the National University of Singapore, and his colleagues.

Raising consumption by more than 0.5 servings per day was associated with a 48% rise in diabetes risk during the next 4 years in the study population as a whole. And even among nonobese adults, increasing intake by 0.5 servings per day was associated with a 65% greater risk of diabetes, the investigators said (JAMA Intern. Med. 2013 June 17 [doi:10.1001/jamainternmed.2013.6633]).

Diabetes risk was "modestly" attenuated when the data were adjusted to account for the concurrent weight gain that often accompanied greater intake of red meat. This suggests that weight gain accounted for some, but not all, of the association between red meat intake and diabetes.

In addition, the association was stronger for processed than for nonprocessed red meats.

Unfortunately, study subjects who cut back on red meat did not show a significant reduction in diabetes risk during the ensuing 4 years. However, the highest reduction of red meat intake – decreasing consumption by more than 0.5 servings per day during the initial 4 years of follow-up – was associated with a 10% lower risk of diabetes by the end of the entire follow-up of 16 years after adjustment for BMI plus concurrent weight gain.

This study was limited in that the reasons why subjects increased or decreased their intake of red meat were unknown, and could not be accounted for in the data analysis. In addition, the study subjects were primarily white and well-educated adults, so the findings may not be generalizable to other populations, the researchers said.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Increased consumption of red meat over a 4-year period was associated with higher risk that type 2 diabetes would develop during the next 4 years, according to a report published online June 17 in JAMA Internal Medicine.

This association was strong in both men and women in a large cohort study with 12-16 years of follow-up, regardless of the subjects’ baseline level of red meat intake, the overall quality of their diet, or their body weight, said An Pan, Ph.D., of the department of nutrition, Harvard School of Public Health, Boston, and his associates.

Previous studies, largely cross-sectional, have noted a correlation between the consumption of red meat and current diabetes risk but have had limited duration of follow-up. This is the first study to assess changes in the intake of red meat over time and subsequent diabetes risk, and it confirms the robustness of the association, the investigators said.

©Len Rizzi/National Cancer Institute

However, because this was an observational study, it cannot determine causality, they noted.

Dr. Pan and his colleagues examined the issue using data from three large cohort studies: the Health Professionals Follow-Up Study (HPFS), the Nurses’ Health Study (NHS), and the Nurses’ Health Study II (NHS II). All of these collected measurements of red meat intake every 4 years, as well as other dietary, lifestyle, and medical factors.

For their investigation, Dr. Pan and his associates analyzed data for 26,357 male health care professionals aged 40-75 years at baseline in 1986 and 122,786 female nurses aged 25-55 years at baseline in either 1986 or 1991.

These subjects reported how often, on average, they consumed a standard portion size of red meat, which was defined as beef, pork, or lamb as a main dish; hamburger; beef, pork or lamb as a sandwich or mixed dish; as well as bacon, hot dogs, sausage, salami, bologna, and other processed red meats. The responses ranged from never or less than once per month to six or more times per day.

A total of 7,540 cases of incident type 2 diabetes developed during follow-up: 1,561 in the HPFS, 3,482 in the NHS, and 2,497 in the NHS II.

Compared with people whose intake of red meat was relatively stable during each 4-year period, those who increased their intake were at elevated risk for developing diabetes in all three cohorts, said Dr. Pan, who is also at the National University of Singapore, and his colleagues.

Raising consumption by more than 0.5 servings per day was associated with a 48% rise in diabetes risk during the next 4 years in the study population as a whole. And even among nonobese adults, increasing intake by 0.5 servings per day was associated with a 65% greater risk of diabetes, the investigators said (JAMA Intern. Med. 2013 June 17 [doi:10.1001/jamainternmed.2013.6633]).

Diabetes risk was "modestly" attenuated when the data were adjusted to account for the concurrent weight gain that often accompanied greater intake of red meat. This suggests that weight gain accounted for some, but not all, of the association between red meat intake and diabetes.

In addition, the association was stronger for processed than for nonprocessed red meats.

Unfortunately, study subjects who cut back on red meat did not show a significant reduction in diabetes risk during the ensuing 4 years. However, the highest reduction of red meat intake – decreasing consumption by more than 0.5 servings per day during the initial 4 years of follow-up – was associated with a 10% lower risk of diabetes by the end of the entire follow-up of 16 years after adjustment for BMI plus concurrent weight gain.

This study was limited in that the reasons why subjects increased or decreased their intake of red meat were unknown, and could not be accounted for in the data analysis. In addition, the study subjects were primarily white and well-educated adults, so the findings may not be generalizable to other populations, the researchers said.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

Inhaled racemic adrenaline is no more effective than inhaled saline for infants hospitalized with acute bronchiolitis, according to a report published online June 12 in the New England Journal of Medicine.

In a multicenter, double-blind randomized trial involving 404 infants in Norway, hospital length of stay was no shorter for patients who received inhaled adrenaline than for those who received inhaled saline. The need for nasogastric-tube feeding, supplemental oxygen, or ventilatory support also was no different between the two groups, said Dr. Havard Ove Skjerven of Oslo University Hospital and his associates.

Adrenaline inhalation, which reduces mucosal swelling, is used frequently for acute bronchiolitis in the outpatient setting, chiefly because it has been shown to improve symptoms and prevent the need for hospitalization. "Among inpatients, however, adrenaline has not been found to reduce the length of hospital stay," the investigators noted.

They studied the issue in babies aged younger than 1 year (mean age, 4 months) who were admitted to the pediatric departments of eight hospitals during a 1-year period. A total of 102 infants were randomly assigned to receive inhaled adrenaline on demand, 101 to receive inhaled adrenaline on a fixed schedule, 98 to receive saline on demand, and 103 to receive saline on a fixed schedule.

The primary outcome was length of hospital stay. The mean length of stay for the entire study population was 80 hours.

There was no significant difference in length of hospital stay between the infants treated with adrenaline (78.7 hours) and those treated with saline (81.8 hours).

There also were no significant between-group differences in the need for feeding using a nasogastric tube, supplemental oxygen, or ventilatory support. the researchers said (N. Engl. J. Med. 2013 June 12 [doi:10.1056/NEHMoa1301839]).

In addition, the infants were scored on a measure of clinical appearance, which took into account their general condition, skin color, findings on auscultation, respiratory rate, and chest retractions. These scores also did not differ significantly between infants given their first dose of inhaled adrenaline and those given their first dose of inhaled saline.

The two study groups also were similar in the number of children who discontinued the study medication. No serious adverse events were reported.

These findings did not change in a subgroup analysis that categorized the infants by age (younger vs. older than 3 months). They also remained robust regardless of whether the patients had a history of atopic eczema or wheezing, or a family history of atopy.

However, it was notable that among the youngest patients (less than 3 months of age), length of hospital stay was significantly shorter and secondary outcomes were better for those who received either adrenaline or saline inhalation on demand than for those who received either drug on a fixed schedule. Because the on-demand groups received a mean of 5 (30%) fewer inhalations than the fixed-schedule groups, this suggests that "minimal handling" – allowing infants to sleep, with minimal interruptions – is the preferred approach for this age group, Dr. Skjerven and his associates said.

This study was supported by Medicines for Children, a publicly funded group administered by Haukeland University Hospital. Dr. Skjerven reported no relevant financial disclosures; his associates reported ties to numerous industry sources.

An intervention that included physician education and auditing of antibiotic prescriptions significantly reduced inappropriate prescribing for acute respiratory tract infections in a study of a large pediatric primary care network, according to a report in the June 12 issue of JAMA

During the course of 1 year, the intervention nearly halved prescribing of broad-spectrum antibiotics at visits for acute sinusitis and strep pharyngitis, and also cut the off-guideline prescription of antibiotics for acute pneumonia by 75%, said Dr. Jeffrey S. Gerber of the division of infectious diseases at Children’s Hospital of Philadelphia, and his associates.

The intervention was modeled on antimicrobial stewardship programs used in hospitals, which have been shown to reduce the use of antibiotics, improve patient outcomes, and reduce health care costs for both pediatric and adult inpatients. "Our findings suggest that extending antimicrobial stewardship to the ambulatory setting, where such programs generally have not been implemented, may have important health benefits," the investigators said.

"Because most antibiotic use occurs in outpatients, it is essential to apply stewardship principles to ambulatory medicine to maximize the population benefits of more judicious antibiotic use, including reduced antibiotic resistance pressure and unnecessary adverse drug effects and health care costs," they noted.

Dr. Gerber and his colleagues assessed the effectiveness of one such stewardship intervention in a cluster-randomized trial involving a hospital-affiliated network of 18 pediatric primary care sites. Nine practice groups were randomly assigned to receive the intervention and nine to serve as controls.

The practices "served children of diverse racial and socioeconomic backgrounds within urban, suburban, and rural settings across southeastern Pennsylvania and southern New Jersey."

Data were collected for the 20 months before the intervention was implemented and the 12 months afterward. This involved 1,291,824 office visits by 185,212 patients to 162 physicians at the 18 practices.

The intervention included a one-time, 1-hour clinician education session delivered at each practice by a physician who was board certified in pediatric infectious diseases. At this session, the study goals were outlined and the pediatricians were updated on current prescribing guidelines for common acute respiratory tract infections.

Prescribing practices for cases of acute sinusitis, streptococcal pharyngitis, and pneumonia were then audited electronically. Patients with chronic diseases and drug allergies were excluded from the study, as were patients who had previously received antibiotics for the index infection.

Every 4 months, each pediatrician received a private feedback report via secure office email on his or her prescribing practices, as well as peer benchmarking.

The control group received no intervention and no feedback.

After 1 year, the prescription of broad-spectrum antibiotics decreased from 26.8% to 14.3% of visits for acute respiratory tract infections in the intervention group. In contrast, this rate decreased only from 28.4% to 22.6% in the control group, Dr. Gerber and his associates said (JAMA 2013;309:2345-52).

In particular, off-guideline prescribing of broad-spectrum antibiotics for pneumonia decreased in the intervention group from 15.7% of cases to 4.2%. In comparison, this rate dropped only from 17.1% to 16.3% in the control group.

Inappropriate prescribing for acute sinusitis decreased from 38.9% to 18.8% in the intervention group, compared with a relatively small drop 40.0% to 33.9% in the control group.

Inappropriate prescribing for strep pharyngitis started low and remained low for both study groups, decreasing from 4.4% to 3.4% with the intervention and from 5.6% to 3.5% in the control group.

The investigators also tracked inappropriate antibiotic prescribing for viral infections. These rates were low at baseline for both groups and did not change significantly during the study.

This study was limited in that it did not examine patient outcomes, so there was no way to assess how prescribing practices may have altered those outcomes. In addition, with only 1 year of follow-up, there is no way to determine whether continued auditing and feedback are necessary to maintain the changes in prescribing patterns, the investigators noted.

This study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Gerber’s associates reported ties to several industry sources.

An intervention that included physician education and auditing of antibiotic prescriptions significantly reduced inappropriate prescribing for acute respiratory tract infections in a study of a large pediatric primary care network, according to a report in the June 12 issue of JAMA

During the course of 1 year, the intervention nearly halved prescribing of broad-spectrum antibiotics at visits for acute sinusitis and strep pharyngitis, and also cut the off-guideline prescription of antibiotics for acute pneumonia by 75%, said Dr. Jeffrey S. Gerber of the division of infectious diseases at Children’s Hospital of Philadelphia, and his associates.

The intervention was modeled on antimicrobial stewardship programs used in hospitals, which have been shown to reduce the use of antibiotics, improve patient outcomes, and reduce health care costs for both pediatric and adult inpatients. "Our findings suggest that extending antimicrobial stewardship to the ambulatory setting, where such programs generally have not been implemented, may have important health benefits," the investigators said.

"Because most antibiotic use occurs in outpatients, it is essential to apply stewardship principles to ambulatory medicine to maximize the population benefits of more judicious antibiotic use, including reduced antibiotic resistance pressure and unnecessary adverse drug effects and health care costs," they noted.

Dr. Gerber and his colleagues assessed the effectiveness of one such stewardship intervention in a cluster-randomized trial involving a hospital-affiliated network of 18 pediatric primary care sites. Nine practice groups were randomly assigned to receive the intervention and nine to serve as controls.

The practices "served children of diverse racial and socioeconomic backgrounds within urban, suburban, and rural settings across southeastern Pennsylvania and southern New Jersey."

Data were collected for the 20 months before the intervention was implemented and the 12 months afterward. This involved 1,291,824 office visits by 185,212 patients to 162 physicians at the 18 practices.

The intervention included a one-time, 1-hour clinician education session delivered at each practice by a physician who was board certified in pediatric infectious diseases. At this session, the study goals were outlined and the pediatricians were updated on current prescribing guidelines for common acute respiratory tract infections.

Prescribing practices for cases of acute sinusitis, streptococcal pharyngitis, and pneumonia were then audited electronically. Patients with chronic diseases and drug allergies were excluded from the study, as were patients who had previously received antibiotics for the index infection.

Every 4 months, each pediatrician received a private feedback report via secure office email on his or her prescribing practices, as well as peer benchmarking.

The control group received no intervention and no feedback.

After 1 year, the prescription of broad-spectrum antibiotics decreased from 26.8% to 14.3% of visits for acute respiratory tract infections in the intervention group. In contrast, this rate decreased only from 28.4% to 22.6% in the control group, Dr. Gerber and his associates said (JAMA 2013;309:2345-52).

In particular, off-guideline prescribing of broad-spectrum antibiotics for pneumonia decreased in the intervention group from 15.7% of cases to 4.2%. In comparison, this rate dropped only from 17.1% to 16.3% in the control group.

Inappropriate prescribing for acute sinusitis decreased from 38.9% to 18.8% in the intervention group, compared with a relatively small drop 40.0% to 33.9% in the control group.

Inappropriate prescribing for strep pharyngitis started low and remained low for both study groups, decreasing from 4.4% to 3.4% with the intervention and from 5.6% to 3.5% in the control group.

The investigators also tracked inappropriate antibiotic prescribing for viral infections. These rates were low at baseline for both groups and did not change significantly during the study.

This study was limited in that it did not examine patient outcomes, so there was no way to assess how prescribing practices may have altered those outcomes. In addition, with only 1 year of follow-up, there is no way to determine whether continued auditing and feedback are necessary to maintain the changes in prescribing patterns, the investigators noted.

This study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Gerber’s associates reported ties to several industry sources.

An intervention that included physician education and auditing of antibiotic prescriptions significantly reduced inappropriate prescribing for acute respiratory tract infections in a study of a large pediatric primary care network, according to a report in the June 12 issue of JAMA

During the course of 1 year, the intervention nearly halved prescribing of broad-spectrum antibiotics at visits for acute sinusitis and strep pharyngitis, and also cut the off-guideline prescription of antibiotics for acute pneumonia by 75%, said Dr. Jeffrey S. Gerber of the division of infectious diseases at Children’s Hospital of Philadelphia, and his associates.

The intervention was modeled on antimicrobial stewardship programs used in hospitals, which have been shown to reduce the use of antibiotics, improve patient outcomes, and reduce health care costs for both pediatric and adult inpatients. "Our findings suggest that extending antimicrobial stewardship to the ambulatory setting, where such programs generally have not been implemented, may have important health benefits," the investigators said.

"Because most antibiotic use occurs in outpatients, it is essential to apply stewardship principles to ambulatory medicine to maximize the population benefits of more judicious antibiotic use, including reduced antibiotic resistance pressure and unnecessary adverse drug effects and health care costs," they noted.

Dr. Gerber and his colleagues assessed the effectiveness of one such stewardship intervention in a cluster-randomized trial involving a hospital-affiliated network of 18 pediatric primary care sites. Nine practice groups were randomly assigned to receive the intervention and nine to serve as controls.

The practices "served children of diverse racial and socioeconomic backgrounds within urban, suburban, and rural settings across southeastern Pennsylvania and southern New Jersey."

Data were collected for the 20 months before the intervention was implemented and the 12 months afterward. This involved 1,291,824 office visits by 185,212 patients to 162 physicians at the 18 practices.

The intervention included a one-time, 1-hour clinician education session delivered at each practice by a physician who was board certified in pediatric infectious diseases. At this session, the study goals were outlined and the pediatricians were updated on current prescribing guidelines for common acute respiratory tract infections.

Prescribing practices for cases of acute sinusitis, streptococcal pharyngitis, and pneumonia were then audited electronically. Patients with chronic diseases and drug allergies were excluded from the study, as were patients who had previously received antibiotics for the index infection.

Every 4 months, each pediatrician received a private feedback report via secure office email on his or her prescribing practices, as well as peer benchmarking.

The control group received no intervention and no feedback.

After 1 year, the prescription of broad-spectrum antibiotics decreased from 26.8% to 14.3% of visits for acute respiratory tract infections in the intervention group. In contrast, this rate decreased only from 28.4% to 22.6% in the control group, Dr. Gerber and his associates said (JAMA 2013;309:2345-52).

In particular, off-guideline prescribing of broad-spectrum antibiotics for pneumonia decreased in the intervention group from 15.7% of cases to 4.2%. In comparison, this rate dropped only from 17.1% to 16.3% in the control group.

Inappropriate prescribing for acute sinusitis decreased from 38.9% to 18.8% in the intervention group, compared with a relatively small drop 40.0% to 33.9% in the control group.

Inappropriate prescribing for strep pharyngitis started low and remained low for both study groups, decreasing from 4.4% to 3.4% with the intervention and from 5.6% to 3.5% in the control group.

The investigators also tracked inappropriate antibiotic prescribing for viral infections. These rates were low at baseline for both groups and did not change significantly during the study.

This study was limited in that it did not examine patient outcomes, so there was no way to assess how prescribing practices may have altered those outcomes. In addition, with only 1 year of follow-up, there is no way to determine whether continued auditing and feedback are necessary to maintain the changes in prescribing patterns, the investigators noted.

This study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Gerber’s associates reported ties to several industry sources.