Mary Ann Moon

Information pooled in a meta-analysis of 18 data sets may allow clinicians to fine-tune the ultrasonographic surveillance of small abdominal aortic aneurysms, according to a report in the Feb. 27 issue of JAMA.

"Currently, there is no consensus regarding appropriate surveillance intervals for patients with (AAAs) [abdominal aortic aneurysms]. By pooling results from 18 studies, we quantified AAA growth rates and the AAA rupture risk as a function of aortic diameter. Our intent was to provide an objective basis for selecting surveillance intervals for patients with small AAAs," said Simon G. Thompson, D.Sc., of the cardiovascular epidemiology unit, department of public health and primary care, University of Cambridge (England), and his associates.

Their findings suggest that the overall number and frequency of surveillance scans can be reduced, at least for men. However, the picture is still unclear for women, and more research is required before specific recommendations can be made, the investigators said.

Dr. Thompson and his colleagues reviewed randomized trials, observational studies, and papers presented at vascular surgical conferences that included data sets with 100 or more patients who underwent repeated ultrasound measurements of the diameter of AAAs over time. This yielded 18 data sets that included 15,471 subjects with AAA diameters between 3.0 and 5.4 cm, because 5.5 cm is usually the threshold at which surgical repair of the lesion is recommended.

The 13,728 men and 1,743 women were followed for an average of 1-8 years. There were "relatively few" AAA ruptures: 178 among men and 50 among women.

Among men, a 3-cm AAA took a mean of 7.4 years to have a 10% chance of reaching 5.5 cm, a 4-cm AAA took a mean of 3.2 years to have a 10% chance of reaching 5.5 cm, and a 5-cm AAA took a mean of 0.7 years to have a 10% chance of reaching 5.5 cm.

Similarly, rupture rates among men approximately doubled for every 0.5-cm increase in AAA diameter. For AAAs with diameters of 3.0-4.5 cm, the average time to reach a rupture risk of 1% was at least 2 years.

These data can be used to guide the decision of how often to perform ultrasound surveillance of AAAs in men. Based on the lower 95% confidence limits, the risk of rupture in men would be less than 1% if surveillance intervals were extended to 3 years for AAAs measuring 3.0-3.9 cm, to 2 years for those measuring 4.0-4.4 cm, and to 1 year for those measuring 4.5-5.4 cm.

"For a U.S. patient with a 3.0-cm AAA detected by screening, this would reduce the average number of surveillance scans from approximately 15 to 7," the investigators wrote (JAMA 2013;309:806-13).

However, if the lower 95% prediction limits of the estimates were applied (to acknowledge that the population in each study might have different growth and rupture rates), the risk of rupture in men would be less than 1% if surveillance intervals were extended to 2 years for AAAs measuring 3.0-3.9 cm, to 1 year for those measuring 4.0-4.9 cm, and to 6 months for those measuring 5.0-5.4 cm. This would result in a lesser average reduction in the number of surveillance scans from 15 to 10.

The rate of rupture was four times higher for women than for men, even though the rate of AAA growth was similar. The higher risk of AAA rupture in women is well known, although the reasons for this discrepancy are not yet certain. Researchers have proposed that differences in anatomy, structure, sex hormones, and smoking habits all may play a role.

"The clinical implication is that a lower AAA diameter threshold for surgery should be adopted for women, a recommendation already made by the joint council of the American Association for Vascular Surgery and the Society for Vascular Surgery," Dr. Thompson and his associates wrote.

A threshold of 4.5 cm rather than 5.5 cm might be more appropriate for women, but this decision must be weighed against the evidence that women have a higher operative mortality than men and a poorer outcome at postoperative hospital discharge, the investigators noted.

This study was supported by the U.K. National Institute for Health Research’s Health Technology Assessment Programme. The authors reported that they had no relevant financial conflicts, although individual members had participated in aneurysm clinical trials.

Information pooled in a meta-analysis of 18 data sets may allow clinicians to fine-tune the ultrasonographic surveillance of small abdominal aortic aneurysms, according to a report in the Feb. 27 issue of JAMA.

"Currently, there is no consensus regarding appropriate surveillance intervals for patients with (AAAs) [abdominal aortic aneurysms]. By pooling results from 18 studies, we quantified AAA growth rates and the AAA rupture risk as a function of aortic diameter. Our intent was to provide an objective basis for selecting surveillance intervals for patients with small AAAs," said Simon G. Thompson, D.Sc., of the cardiovascular epidemiology unit, department of public health and primary care, University of Cambridge (England), and his associates.

Their findings suggest that the overall number and frequency of surveillance scans can be reduced, at least for men. However, the picture is still unclear for women, and more research is required before specific recommendations can be made, the investigators said.

Dr. Thompson and his colleagues reviewed randomized trials, observational studies, and papers presented at vascular surgical conferences that included data sets with 100 or more patients who underwent repeated ultrasound measurements of the diameter of AAAs over time. This yielded 18 data sets that included 15,471 subjects with AAA diameters between 3.0 and 5.4 cm, because 5.5 cm is usually the threshold at which surgical repair of the lesion is recommended.

The 13,728 men and 1,743 women were followed for an average of 1-8 years. There were "relatively few" AAA ruptures: 178 among men and 50 among women.

Among men, a 3-cm AAA took a mean of 7.4 years to have a 10% chance of reaching 5.5 cm, a 4-cm AAA took a mean of 3.2 years to have a 10% chance of reaching 5.5 cm, and a 5-cm AAA took a mean of 0.7 years to have a 10% chance of reaching 5.5 cm.

Similarly, rupture rates among men approximately doubled for every 0.5-cm increase in AAA diameter. For AAAs with diameters of 3.0-4.5 cm, the average time to reach a rupture risk of 1% was at least 2 years.

These data can be used to guide the decision of how often to perform ultrasound surveillance of AAAs in men. Based on the lower 95% confidence limits, the risk of rupture in men would be less than 1% if surveillance intervals were extended to 3 years for AAAs measuring 3.0-3.9 cm, to 2 years for those measuring 4.0-4.4 cm, and to 1 year for those measuring 4.5-5.4 cm.

"For a U.S. patient with a 3.0-cm AAA detected by screening, this would reduce the average number of surveillance scans from approximately 15 to 7," the investigators wrote (JAMA 2013;309:806-13).

However, if the lower 95% prediction limits of the estimates were applied (to acknowledge that the population in each study might have different growth and rupture rates), the risk of rupture in men would be less than 1% if surveillance intervals were extended to 2 years for AAAs measuring 3.0-3.9 cm, to 1 year for those measuring 4.0-4.9 cm, and to 6 months for those measuring 5.0-5.4 cm. This would result in a lesser average reduction in the number of surveillance scans from 15 to 10.

The rate of rupture was four times higher for women than for men, even though the rate of AAA growth was similar. The higher risk of AAA rupture in women is well known, although the reasons for this discrepancy are not yet certain. Researchers have proposed that differences in anatomy, structure, sex hormones, and smoking habits all may play a role.

"The clinical implication is that a lower AAA diameter threshold for surgery should be adopted for women, a recommendation already made by the joint council of the American Association for Vascular Surgery and the Society for Vascular Surgery," Dr. Thompson and his associates wrote.

A threshold of 4.5 cm rather than 5.5 cm might be more appropriate for women, but this decision must be weighed against the evidence that women have a higher operative mortality than men and a poorer outcome at postoperative hospital discharge, the investigators noted.

This study was supported by the U.K. National Institute for Health Research’s Health Technology Assessment Programme. The authors reported that they had no relevant financial conflicts, although individual members had participated in aneurysm clinical trials.

Information pooled in a meta-analysis of 18 data sets may allow clinicians to fine-tune the ultrasonographic surveillance of small abdominal aortic aneurysms, according to a report in the Feb. 27 issue of JAMA.

"Currently, there is no consensus regarding appropriate surveillance intervals for patients with (AAAs) [abdominal aortic aneurysms]. By pooling results from 18 studies, we quantified AAA growth rates and the AAA rupture risk as a function of aortic diameter. Our intent was to provide an objective basis for selecting surveillance intervals for patients with small AAAs," said Simon G. Thompson, D.Sc., of the cardiovascular epidemiology unit, department of public health and primary care, University of Cambridge (England), and his associates.

Their findings suggest that the overall number and frequency of surveillance scans can be reduced, at least for men. However, the picture is still unclear for women, and more research is required before specific recommendations can be made, the investigators said.

Dr. Thompson and his colleagues reviewed randomized trials, observational studies, and papers presented at vascular surgical conferences that included data sets with 100 or more patients who underwent repeated ultrasound measurements of the diameter of AAAs over time. This yielded 18 data sets that included 15,471 subjects with AAA diameters between 3.0 and 5.4 cm, because 5.5 cm is usually the threshold at which surgical repair of the lesion is recommended.

The 13,728 men and 1,743 women were followed for an average of 1-8 years. There were "relatively few" AAA ruptures: 178 among men and 50 among women.

Among men, a 3-cm AAA took a mean of 7.4 years to have a 10% chance of reaching 5.5 cm, a 4-cm AAA took a mean of 3.2 years to have a 10% chance of reaching 5.5 cm, and a 5-cm AAA took a mean of 0.7 years to have a 10% chance of reaching 5.5 cm.

Similarly, rupture rates among men approximately doubled for every 0.5-cm increase in AAA diameter. For AAAs with diameters of 3.0-4.5 cm, the average time to reach a rupture risk of 1% was at least 2 years.

These data can be used to guide the decision of how often to perform ultrasound surveillance of AAAs in men. Based on the lower 95% confidence limits, the risk of rupture in men would be less than 1% if surveillance intervals were extended to 3 years for AAAs measuring 3.0-3.9 cm, to 2 years for those measuring 4.0-4.4 cm, and to 1 year for those measuring 4.5-5.4 cm.

"For a U.S. patient with a 3.0-cm AAA detected by screening, this would reduce the average number of surveillance scans from approximately 15 to 7," the investigators wrote (JAMA 2013;309:806-13).

However, if the lower 95% prediction limits of the estimates were applied (to acknowledge that the population in each study might have different growth and rupture rates), the risk of rupture in men would be less than 1% if surveillance intervals were extended to 2 years for AAAs measuring 3.0-3.9 cm, to 1 year for those measuring 4.0-4.9 cm, and to 6 months for those measuring 5.0-5.4 cm. This would result in a lesser average reduction in the number of surveillance scans from 15 to 10.

The rate of rupture was four times higher for women than for men, even though the rate of AAA growth was similar. The higher risk of AAA rupture in women is well known, although the reasons for this discrepancy are not yet certain. Researchers have proposed that differences in anatomy, structure, sex hormones, and smoking habits all may play a role.

"The clinical implication is that a lower AAA diameter threshold for surgery should be adopted for women, a recommendation already made by the joint council of the American Association for Vascular Surgery and the Society for Vascular Surgery," Dr. Thompson and his associates wrote.

A threshold of 4.5 cm rather than 5.5 cm might be more appropriate for women, but this decision must be weighed against the evidence that women have a higher operative mortality than men and a poorer outcome at postoperative hospital discharge, the investigators noted.

This study was supported by the U.K. National Institute for Health Research’s Health Technology Assessment Programme. The authors reported that they had no relevant financial conflicts, although individual members had participated in aneurysm clinical trials.

The incidence of breast cancer presenting with distant involvement has risen significantly over the past 30 years among young women, and this trend shows no signs of abating, according to a report in the Feb. 27 issue of JAMA.

In contrast, the rate of locoregional breast cancer has not increased in this age group, and the incidence of all stages of the disease have not shown any increasing trends among older women, said Dr. Rebecca H. Johnson of Seattle Children’s Hospital and the University of Washington, Seattle, and her associates.

This trajectory "predicts that an increasing number of young women in the United States will present with metastatic breast cancer in an age group that already has the worst prognosis, no recommended routine screening practice, the least health insurance, and the most potential years of life" lost, the investigators noted.

They used data from three of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registries to examine time trends in breast cancer between 1976 and 2009. They found a steady, and possibly accelerating, rise in the rate of women aged 25-39 years presenting with metastatic breast cancer, from 1.53/100,000 in 1976 to 2.90/100,000 in 2009.

"No other age group had statistically significant increases, either for distant, regional, or localized disease at diagnosis," Dr. Johnson and her colleagues said (JAMA 2013;309:800-5).

In a different analysis of the data, the category of metastatic breast cancer as a proportion of all invasive breast cancer in this age group rose from 4.4% in the 1970s to 4.8% in the 1980s, 5.5% in the 1990s, and 7.2% in the early 2000s.

This trend was evident in women of all races/ethnicities, in women residing in both urban and nonurban regions, and in women with estrogen receptor–positive and estrogen receptor–negative tumors. "Non-Hispanic white and African-American individuals appear to have been more affected by the increase, as have women with the ER-positive subtype of the disease," they said.

"The absolute increase of 1.37/100,000 over 34 years is relatively small, but the trend shows no evidence of abatement and may indicate increasing epidemiologic and clinical significance," the researchers said.

These findings must be corroborated in other studies. If they are confirmed, they will be particularly concerning "because young age itself is an independent adverse prognostic factor for breast cancer.

"The most recent national 5-year survival data for distant disease for 25- to 39-year-old women is only 31% ... compared with a 5-year survival of 87% for women with locoregional breast cancer," they added.

Dr. Johnson reported having served on a board for Critical Mass Young Adult Cancer Alliance and having served as a speaker at the Leukemia and Lymphoma Society AYA Survivorship Conference. One of her colleagues reported being a consultant and speaker for Sigma-Tau Pharmaceuticals; another researcher’s salary was funded by the Seattle Children’s Guild Association Teen Cancer Grant. No other disclosures were reported.

tor@elsevier.com

The incidence of breast cancer presenting with distant involvement has risen significantly over the past 30 years among young women, and this trend shows no signs of abating, according to a report in the Feb. 27 issue of JAMA.

In contrast, the rate of locoregional breast cancer has not increased in this age group, and the incidence of all stages of the disease have not shown any increasing trends among older women, said Dr. Rebecca H. Johnson of Seattle Children’s Hospital and the University of Washington, Seattle, and her associates.

This trajectory "predicts that an increasing number of young women in the United States will present with metastatic breast cancer in an age group that already has the worst prognosis, no recommended routine screening practice, the least health insurance, and the most potential years of life" lost, the investigators noted.

They used data from three of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registries to examine time trends in breast cancer between 1976 and 2009. They found a steady, and possibly accelerating, rise in the rate of women aged 25-39 years presenting with metastatic breast cancer, from 1.53/100,000 in 1976 to 2.90/100,000 in 2009.

"No other age group had statistically significant increases, either for distant, regional, or localized disease at diagnosis," Dr. Johnson and her colleagues said (JAMA 2013;309:800-5).

In a different analysis of the data, the category of metastatic breast cancer as a proportion of all invasive breast cancer in this age group rose from 4.4% in the 1970s to 4.8% in the 1980s, 5.5% in the 1990s, and 7.2% in the early 2000s.

This trend was evident in women of all races/ethnicities, in women residing in both urban and nonurban regions, and in women with estrogen receptor–positive and estrogen receptor–negative tumors. "Non-Hispanic white and African-American individuals appear to have been more affected by the increase, as have women with the ER-positive subtype of the disease," they said.

"The absolute increase of 1.37/100,000 over 34 years is relatively small, but the trend shows no evidence of abatement and may indicate increasing epidemiologic and clinical significance," the researchers said.

These findings must be corroborated in other studies. If they are confirmed, they will be particularly concerning "because young age itself is an independent adverse prognostic factor for breast cancer.

"The most recent national 5-year survival data for distant disease for 25- to 39-year-old women is only 31% ... compared with a 5-year survival of 87% for women with locoregional breast cancer," they added.

Dr. Johnson reported having served on a board for Critical Mass Young Adult Cancer Alliance and having served as a speaker at the Leukemia and Lymphoma Society AYA Survivorship Conference. One of her colleagues reported being a consultant and speaker for Sigma-Tau Pharmaceuticals; another researcher’s salary was funded by the Seattle Children’s Guild Association Teen Cancer Grant. No other disclosures were reported.

tor@elsevier.com

The incidence of breast cancer presenting with distant involvement has risen significantly over the past 30 years among young women, and this trend shows no signs of abating, according to a report in the Feb. 27 issue of JAMA.

In contrast, the rate of locoregional breast cancer has not increased in this age group, and the incidence of all stages of the disease have not shown any increasing trends among older women, said Dr. Rebecca H. Johnson of Seattle Children’s Hospital and the University of Washington, Seattle, and her associates.

This trajectory "predicts that an increasing number of young women in the United States will present with metastatic breast cancer in an age group that already has the worst prognosis, no recommended routine screening practice, the least health insurance, and the most potential years of life" lost, the investigators noted.

They used data from three of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registries to examine time trends in breast cancer between 1976 and 2009. They found a steady, and possibly accelerating, rise in the rate of women aged 25-39 years presenting with metastatic breast cancer, from 1.53/100,000 in 1976 to 2.90/100,000 in 2009.

"No other age group had statistically significant increases, either for distant, regional, or localized disease at diagnosis," Dr. Johnson and her colleagues said (JAMA 2013;309:800-5).

In a different analysis of the data, the category of metastatic breast cancer as a proportion of all invasive breast cancer in this age group rose from 4.4% in the 1970s to 4.8% in the 1980s, 5.5% in the 1990s, and 7.2% in the early 2000s.

This trend was evident in women of all races/ethnicities, in women residing in both urban and nonurban regions, and in women with estrogen receptor–positive and estrogen receptor–negative tumors. "Non-Hispanic white and African-American individuals appear to have been more affected by the increase, as have women with the ER-positive subtype of the disease," they said.

"The absolute increase of 1.37/100,000 over 34 years is relatively small, but the trend shows no evidence of abatement and may indicate increasing epidemiologic and clinical significance," the researchers said.

These findings must be corroborated in other studies. If they are confirmed, they will be particularly concerning "because young age itself is an independent adverse prognostic factor for breast cancer.

"The most recent national 5-year survival data for distant disease for 25- to 39-year-old women is only 31% ... compared with a 5-year survival of 87% for women with locoregional breast cancer," they added.

Dr. Johnson reported having served on a board for Critical Mass Young Adult Cancer Alliance and having served as a speaker at the Leukemia and Lymphoma Society AYA Survivorship Conference. One of her colleagues reported being a consultant and speaker for Sigma-Tau Pharmaceuticals; another researcher’s salary was funded by the Seattle Children’s Guild Association Teen Cancer Grant. No other disclosures were reported.

tor@elsevier.com

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

rhnews@elsevier.com

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

rhnews@elsevier.com

Smoking significantly raises the risk that patients with systemic lupus erythematosus will develop active cutaneous manifestations of the disease, based on data from a multicenter cohort study of 1,346 patients.

Overall, current smokers were 63% more likely than former or never smokers to have an active SLE rash after controlling for multiple variables. In addition, patients who had ever smoked were more than twice as likely to meet the American College of Rheumatology criteria for discoid rash (odds ratio, 2.36) and photosensitivity (odds ratio, 1.47).

©pmphoto/iStockphoto.com

The study is the largest to date examining the effect of smoking on cutaneous outcomes in systemic lupus erythematosus (SLE), said Dr. Josiane Bourré-Tessier of the University of Montreal and her associates.

The researchers examined a possible association between smoking status and skin activity using data from the 1000 Faces of Lupus Cohort, a cohort of SLE patients who presented for care at 14 participating specialty clinics across Canada. The study population included 1,346 participants aged 16 years and older who enrolled between 2005 and 2009 (Arthritis Care Res. 2013 Feb. 11 [doi:10.1002/acr.21966]).

The patients were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), which focuses on rash and alopecia; the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), which focuses on alopecia, extensive scarring, and skin ulceration; and the American College of Rheumatology (ACR) revised criteria for SLE, which focus on discoid rash, malar rash, and photosensitivity.

More than 90% of the study subjects were women, and 63% were white. The mean age was 47 years; mean disease duration was 13 years. Approximately 14% of the patients were current smokers and 27% were past smokers.

Most patients (70%) were taking antimalarials at the time of the study – 64% taking hydroxychloroquine and 6% taking chloroquine. Another 35% were taking immunosuppressants.

According to the SLEDAI-2K, 28% of patients had some mucocutaneous disease activity: 15% had rash, 13% had alopecia, 8% had mucosal ulcers, and 8% had at least two of these symptoms. According to the SDI, 12% had alopecia, including 4% with extensive scarring and 0.2% with skin ulceration. According to ACR criteria, 60% of patients had ever experienced malar rash; 17% had experienced discoid rash; 56%, photosensitivity; and 56%, ulcerations.

No association was found between past smoking and active skin manifestations, based on the SLEDAI-2K.

Based on the SDI, there was no association between smoking and cutaneous damage. This finding, however, may be due to the small number of patients with cutaneous damage, the researchers said. Alternatively, it may suggest that a longer observation period is needed to show a relationship between smoking and long-term cutaneous damage.

Both current and past smoking were associated with discoid rash and photosensitivity, based on the ACR criteria. Since ACR criteria are cumulative, this finding suggests that past smoking "may have triggered the prior emergence of cutaneous criteria," Dr. Bourré-Tessier and her associates said.

The association between smoking and skin manifestations of SLE "is not surprising, as cigarettes contain multiple chemical factors that may generate free radicals and alter inflammatory cell function and extracellular matrix turnover," the researchers wrote.

"These chemical factors may also interact with DNA and promote the production of autoantibodies directed against altered DNA," they suggested.

It was encouraging to find that current, but not past, smoking was associated with skin activity because that suggests the adverse effect may be reversible if patients stop smoking, the researchers noted.

The findings support the results of previous investigations showing that smoking promotes disease activity in a variety of autoimmune conditions. The data also give clinicians added incentive to encourage SLE patients to quit smoking, Dr. Bourré-Tessier and her associates said.

The study was limited by an inability to account for potential confounders such as medication adherence and sun exposure, they added.

The 1000 Faces of Lupus Cohort was funded by the Arthritis Society and the Lupus Society of Manitoba. No financial conflicts of interest were reported.

rhnews@elsevier.com

Two oral anticoagulants, apixaban and dabigatran, were found to be effective for the extended treatment of venous thromboembolism in three industry-sponsored randomized clinical trials. The results were published online Feb. 21 in the New England Journal of Medicine.

Both medications also reduced the risk of bleeding complications, the investigators said.

In the first trial, two doses of apixaban were compared against placebo in 2,486 patients with venous thromboembolism who had finished 6-12 months of standard anticoagulation therapy and whose physicians were uncertain whether to stop or continue anticoagulation treatment, said Dr. Giancarlo Agnelli and his associates in the Apixaban after the Initial Management of Pulmonary Embolism and DVT with First-Line Therapy–Extended Treatment (AMPLIFY-EXT) study.

Apixaban is an oral factor Xa inhibitor that is administered in fixed doses and doesn’t require laboratory monitoring. The 5-mg (treatment) dose of apixaban has proved effective at preventing stroke in patients with atrial fibrillation, and the 2.5-mg (maintenance) dose has proved effective for thromboprophylaxis after major orthopedic surgery, said Dr. Agnelli of the department of internal and cardiovascular medicine-stroke unit at the University of Perugia (Italy) and his colleagues.

The study subjects were enrolled over a 3-year period at 328 medical centers in 28 countries. They were randomly assigned in double-blind fashion to receive the 2.5-mg dose (840 subjects), the 5-mg dose (813 subjects), or a matching placebo (829 subjects) twice daily for 1 year.

The primary efficacy outcome measure was a composite of symptomatic recurrent VTE or death from any cause. This occurred in 3.8% of the maintenance-dose group and 4.2% of the treatment-dose group, both significantly lower rates than in the placebo group (11.6%). Thus, both doses of apixaban significantly decreased the incidence of recurrent VTE, Dr. Agnelli and his associates said (N. Engl. J. Med. 2013 Feb. 21 [doi10.1056/NEJMoa1207541]).

The primary safety outcome measure was major bleeding, which occurred in 0.2% of the maintenance-dose group and 0.1% of the treatment-dose group, compared with 0.5% of the placebo group. Thus, both doses of apixaban were comparable to placebo in rates of major bleeding.

Clinically relevant nonmajor bleeding occurred in 3.0% of subjects taking 2.5 mg of apixaban and 4.2% of those taking 5 mg of apixaban, which were significantly higher than the 2.3% rate in subjects taking placebo.

The number of patients who would need to be treated with apixaban to prevent a single episode of recurrent VTE was 14. In contrast, the number who would need to be treated to cause an episode of major or clinically relevant nonmajor bleeding was 200, the investigators noted.

"For patients with venous thromboembolism for whom there is uncertainty about the benefits and risks of continued therapy, the results of this study provide a rationale for continuing anticoagulation therapy for an additional 12 months," they said.

"It should be noted, however, that only 15% of the patients in this study were older than 75 years of age, and few had a body weight below 60 kg or moderate or severe renal impairment. Consequently, more data are needed to better determine the benefit-to-risk profile of apixaban with respect to bleeding in such patients," the researchers said.

Further research also is needed to determine the risks and benefits of extending anticoagulation therapy beyond the 12-month mark examined in this study, they added.

In a separate report, Dr. Sam Schulman and his associates in the RE-MEDY and RE-SONATE studies examined the direct thrombin inhibitor dabigatran as a long-term anticoagulation treatment. These trials were extensions of two previous studies of short-term anticoagulation after venous thromboembolism (N. Engl. J. Med. 2013 Feb. 21 [doi:10.1056/NEJMoa1113697]).

In RE-MEDY*, 2,866 VTE patients who had completed at least 3 months of anticoagulation therapy and were considered to be at increased risk for recurrence were randomly assigned to receive either fixed-dose dabigatran twice daily (1,430 subjects) or warfarin (1,426 subjects) for up to 36 months. They were followed at 265 medical centers in 33 countries, said Dr. Schulman of McMaster University Thrombosis and Atherosclerosis Research Institute, Hamilton, Ont., and his colleagues.

The RE-SONATE* trial, in contrast, involved 1,343 VTE patients who had completed at least 3 months of anticoagulation therapy but were not considered to be at increased risk of recurrence, so it was ethical to assess the effect of dabigatran vs. placebo in these patients. The subjects were randomly assigned to receive either fixed-dose dabigatran (681 patients) or a matching placebo (662 patients) and were followed at 147 medical centers in 21 countries.

In both RE-SONATE and RE-MEDY, the primary efficacy outcome measure was recurrent symptomatic VTE or VTE-related death.

In RE-MEDY, this outcome occurred in 1.8% of the dabigatran group and 1.3% of the warfarin group, thus meeting the criteria for noninferiority to warfarin in preventing recurrent or fatal VTE.

In RE-SONATE, this outcome occurred in 0.4% of the dabigatran group, compared with 5.6% of the placebo group, so the drug was significantly more effective than placebo at preventing recurrent or fatal VTE.

Dabigatran was associated with markedly fewer major bleeding events (0.9% vs. 1.8%) and clinically relevant bleeding events (5.6% vs. 10.2%) than was warfarin. However, the drug was associated with more major or clinically relevant bleeding events than was placebo (5.3% vs 1.8%).

In addition, there was a higher rate of acute coronary events with dabigatran (0.9%) than with warfarin (0.2%), although the number of affected patients was small. A recent meta-analysis of seven noninferiority trials also showed a significantly higher risk of MI or acute coronary syndromes with dabigatran than with the comparators. "Whether dabigatran increases the risk of MI is therefore still unclear," Dr. Schulman and his associates said.

AMPLIFY-EXT was funded by Bristol-Myers Squibb (BMS) and Pfizer; Dr. Agnelli reported ties to Bayer, Boehringer Ingelheim (BI), Daiichi Sankyo, BMS, and Sanofi-Aventis, and his associates reported ties to numerous industry sources. RE-MEDY and RE-SONATE were funded by BI; Dr. Schulman and his associates reported ties to numerous industry sources.

UPDATED 2/21: An earlier version of this article transposed the trial names in this instance only. The names were correct in all other instances.

Two oral anticoagulants, apixaban and dabigatran, were found to be effective for the extended treatment of venous thromboembolism in three industry-sponsored randomized clinical trials. The results were published online Feb. 21 in the New England Journal of Medicine.

Both medications also reduced the risk of bleeding complications, the investigators said.

In the first trial, two doses of apixaban were compared against placebo in 2,486 patients with venous thromboembolism who had finished 6-12 months of standard anticoagulation therapy and whose physicians were uncertain whether to stop or continue anticoagulation treatment, said Dr. Giancarlo Agnelli and his associates in the Apixaban after the Initial Management of Pulmonary Embolism and DVT with First-Line Therapy–Extended Treatment (AMPLIFY-EXT) study.

Apixaban is an oral factor Xa inhibitor that is administered in fixed doses and doesn’t require laboratory monitoring. The 5-mg (treatment) dose of apixaban has proved effective at preventing stroke in patients with atrial fibrillation, and the 2.5-mg (maintenance) dose has proved effective for thromboprophylaxis after major orthopedic surgery, said Dr. Agnelli of the department of internal and cardiovascular medicine-stroke unit at the University of Perugia (Italy) and his colleagues.

The study subjects were enrolled over a 3-year period at 328 medical centers in 28 countries. They were randomly assigned in double-blind fashion to receive the 2.5-mg dose (840 subjects), the 5-mg dose (813 subjects), or a matching placebo (829 subjects) twice daily for 1 year.

The primary efficacy outcome measure was a composite of symptomatic recurrent VTE or death from any cause. This occurred in 3.8% of the maintenance-dose group and 4.2% of the treatment-dose group, both significantly lower rates than in the placebo group (11.6%). Thus, both doses of apixaban significantly decreased the incidence of recurrent VTE, Dr. Agnelli and his associates said (N. Engl. J. Med. 2013 Feb. 21 [doi10.1056/NEJMoa1207541]).

The primary safety outcome measure was major bleeding, which occurred in 0.2% of the maintenance-dose group and 0.1% of the treatment-dose group, compared with 0.5% of the placebo group. Thus, both doses of apixaban were comparable to placebo in rates of major bleeding.

Clinically relevant nonmajor bleeding occurred in 3.0% of subjects taking 2.5 mg of apixaban and 4.2% of those taking 5 mg of apixaban, which were significantly higher than the 2.3% rate in subjects taking placebo.

The number of patients who would need to be treated with apixaban to prevent a single episode of recurrent VTE was 14. In contrast, the number who would need to be treated to cause an episode of major or clinically relevant nonmajor bleeding was 200, the investigators noted.

"For patients with venous thromboembolism for whom there is uncertainty about the benefits and risks of continued therapy, the results of this study provide a rationale for continuing anticoagulation therapy for an additional 12 months," they said.

"It should be noted, however, that only 15% of the patients in this study were older than 75 years of age, and few had a body weight below 60 kg or moderate or severe renal impairment. Consequently, more data are needed to better determine the benefit-to-risk profile of apixaban with respect to bleeding in such patients," the researchers said.

Further research also is needed to determine the risks and benefits of extending anticoagulation therapy beyond the 12-month mark examined in this study, they added.

In a separate report, Dr. Sam Schulman and his associates in the RE-MEDY and RE-SONATE studies examined the direct thrombin inhibitor dabigatran as a long-term anticoagulation treatment. These trials were extensions of two previous studies of short-term anticoagulation after venous thromboembolism (N. Engl. J. Med. 2013 Feb. 21 [doi:10.1056/NEJMoa1113697]).

In RE-MEDY*, 2,866 VTE patients who had completed at least 3 months of anticoagulation therapy and were considered to be at increased risk for recurrence were randomly assigned to receive either fixed-dose dabigatran twice daily (1,430 subjects) or warfarin (1,426 subjects) for up to 36 months. They were followed at 265 medical centers in 33 countries, said Dr. Schulman of McMaster University Thrombosis and Atherosclerosis Research Institute, Hamilton, Ont., and his colleagues.

The RE-SONATE* trial, in contrast, involved 1,343 VTE patients who had completed at least 3 months of anticoagulation therapy but were not considered to be at increased risk of recurrence, so it was ethical to assess the effect of dabigatran vs. placebo in these patients. The subjects were randomly assigned to receive either fixed-dose dabigatran (681 patients) or a matching placebo (662 patients) and were followed at 147 medical centers in 21 countries.

In both RE-SONATE and RE-MEDY, the primary efficacy outcome measure was recurrent symptomatic VTE or VTE-related death.

In RE-MEDY, this outcome occurred in 1.8% of the dabigatran group and 1.3% of the warfarin group, thus meeting the criteria for noninferiority to warfarin in preventing recurrent or fatal VTE.

In RE-SONATE, this outcome occurred in 0.4% of the dabigatran group, compared with 5.6% of the placebo group, so the drug was significantly more effective than placebo at preventing recurrent or fatal VTE.

Dabigatran was associated with markedly fewer major bleeding events (0.9% vs. 1.8%) and clinically relevant bleeding events (5.6% vs. 10.2%) than was warfarin. However, the drug was associated with more major or clinically relevant bleeding events than was placebo (5.3% vs 1.8%).

In addition, there was a higher rate of acute coronary events with dabigatran (0.9%) than with warfarin (0.2%), although the number of affected patients was small. A recent meta-analysis of seven noninferiority trials also showed a significantly higher risk of MI or acute coronary syndromes with dabigatran than with the comparators. "Whether dabigatran increases the risk of MI is therefore still unclear," Dr. Schulman and his associates said.

AMPLIFY-EXT was funded by Bristol-Myers Squibb (BMS) and Pfizer; Dr. Agnelli reported ties to Bayer, Boehringer Ingelheim (BI), Daiichi Sankyo, BMS, and Sanofi-Aventis, and his associates reported ties to numerous industry sources. RE-MEDY and RE-SONATE were funded by BI; Dr. Schulman and his associates reported ties to numerous industry sources.

UPDATED 2/21: An earlier version of this article transposed the trial names in this instance only. The names were correct in all other instances.

Two oral anticoagulants, apixaban and dabigatran, were found to be effective for the extended treatment of venous thromboembolism in three industry-sponsored randomized clinical trials. The results were published online Feb. 21 in the New England Journal of Medicine.

Both medications also reduced the risk of bleeding complications, the investigators said.

In the first trial, two doses of apixaban were compared against placebo in 2,486 patients with venous thromboembolism who had finished 6-12 months of standard anticoagulation therapy and whose physicians were uncertain whether to stop or continue anticoagulation treatment, said Dr. Giancarlo Agnelli and his associates in the Apixaban after the Initial Management of Pulmonary Embolism and DVT with First-Line Therapy–Extended Treatment (AMPLIFY-EXT) study.

Apixaban is an oral factor Xa inhibitor that is administered in fixed doses and doesn’t require laboratory monitoring. The 5-mg (treatment) dose of apixaban has proved effective at preventing stroke in patients with atrial fibrillation, and the 2.5-mg (maintenance) dose has proved effective for thromboprophylaxis after major orthopedic surgery, said Dr. Agnelli of the department of internal and cardiovascular medicine-stroke unit at the University of Perugia (Italy) and his colleagues.

The study subjects were enrolled over a 3-year period at 328 medical centers in 28 countries. They were randomly assigned in double-blind fashion to receive the 2.5-mg dose (840 subjects), the 5-mg dose (813 subjects), or a matching placebo (829 subjects) twice daily for 1 year.

The primary efficacy outcome measure was a composite of symptomatic recurrent VTE or death from any cause. This occurred in 3.8% of the maintenance-dose group and 4.2% of the treatment-dose group, both significantly lower rates than in the placebo group (11.6%). Thus, both doses of apixaban significantly decreased the incidence of recurrent VTE, Dr. Agnelli and his associates said (N. Engl. J. Med. 2013 Feb. 21 [doi10.1056/NEJMoa1207541]).

The primary safety outcome measure was major bleeding, which occurred in 0.2% of the maintenance-dose group and 0.1% of the treatment-dose group, compared with 0.5% of the placebo group. Thus, both doses of apixaban were comparable to placebo in rates of major bleeding.

Clinically relevant nonmajor bleeding occurred in 3.0% of subjects taking 2.5 mg of apixaban and 4.2% of those taking 5 mg of apixaban, which were significantly higher than the 2.3% rate in subjects taking placebo.

The number of patients who would need to be treated with apixaban to prevent a single episode of recurrent VTE was 14. In contrast, the number who would need to be treated to cause an episode of major or clinically relevant nonmajor bleeding was 200, the investigators noted.

"For patients with venous thromboembolism for whom there is uncertainty about the benefits and risks of continued therapy, the results of this study provide a rationale for continuing anticoagulation therapy for an additional 12 months," they said.

"It should be noted, however, that only 15% of the patients in this study were older than 75 years of age, and few had a body weight below 60 kg or moderate or severe renal impairment. Consequently, more data are needed to better determine the benefit-to-risk profile of apixaban with respect to bleeding in such patients," the researchers said.

Further research also is needed to determine the risks and benefits of extending anticoagulation therapy beyond the 12-month mark examined in this study, they added.

In a separate report, Dr. Sam Schulman and his associates in the RE-MEDY and RE-SONATE studies examined the direct thrombin inhibitor dabigatran as a long-term anticoagulation treatment. These trials were extensions of two previous studies of short-term anticoagulation after venous thromboembolism (N. Engl. J. Med. 2013 Feb. 21 [doi:10.1056/NEJMoa1113697]).

In RE-MEDY*, 2,866 VTE patients who had completed at least 3 months of anticoagulation therapy and were considered to be at increased risk for recurrence were randomly assigned to receive either fixed-dose dabigatran twice daily (1,430 subjects) or warfarin (1,426 subjects) for up to 36 months. They were followed at 265 medical centers in 33 countries, said Dr. Schulman of McMaster University Thrombosis and Atherosclerosis Research Institute, Hamilton, Ont., and his colleagues.

The RE-SONATE* trial, in contrast, involved 1,343 VTE patients who had completed at least 3 months of anticoagulation therapy but were not considered to be at increased risk of recurrence, so it was ethical to assess the effect of dabigatran vs. placebo in these patients. The subjects were randomly assigned to receive either fixed-dose dabigatran (681 patients) or a matching placebo (662 patients) and were followed at 147 medical centers in 21 countries.

In both RE-SONATE and RE-MEDY, the primary efficacy outcome measure was recurrent symptomatic VTE or VTE-related death.

In RE-MEDY, this outcome occurred in 1.8% of the dabigatran group and 1.3% of the warfarin group, thus meeting the criteria for noninferiority to warfarin in preventing recurrent or fatal VTE.

In RE-SONATE, this outcome occurred in 0.4% of the dabigatran group, compared with 5.6% of the placebo group, so the drug was significantly more effective than placebo at preventing recurrent or fatal VTE.

Dabigatran was associated with markedly fewer major bleeding events (0.9% vs. 1.8%) and clinically relevant bleeding events (5.6% vs. 10.2%) than was warfarin. However, the drug was associated with more major or clinically relevant bleeding events than was placebo (5.3% vs 1.8%).

In addition, there was a higher rate of acute coronary events with dabigatran (0.9%) than with warfarin (0.2%), although the number of affected patients was small. A recent meta-analysis of seven noninferiority trials also showed a significantly higher risk of MI or acute coronary syndromes with dabigatran than with the comparators. "Whether dabigatran increases the risk of MI is therefore still unclear," Dr. Schulman and his associates said.

AMPLIFY-EXT was funded by Bristol-Myers Squibb (BMS) and Pfizer; Dr. Agnelli reported ties to Bayer, Boehringer Ingelheim (BI), Daiichi Sankyo, BMS, and Sanofi-Aventis, and his associates reported ties to numerous industry sources. RE-MEDY and RE-SONATE were funded by BI; Dr. Schulman and his associates reported ties to numerous industry sources.

UPDATED 2/21: An earlier version of this article transposed the trial names in this instance only. The names were correct in all other instances.

Hydroxyethyl starch, a synthetic colloid used worldwide for acute fluid resuscitation in critically ill patients, appears to significantly raise the risks of mortality and severe renal injury, compared with other resuscitation solutions, according to a systematic review and meta-analysis published in the Feb. 20 issue of JAMA.

The use of hydroxyethyl starch and other colloidal starch solutions has increased "despite their higher cost relative to crystalloid solutions, lack of evidence of their clinical superiority, and pervasive safety concerns," said Dr. Ryan Zarychanski of the section of critical care and the section of hematology and medical oncology, University of Manitoba, Winnipeg, and his associates (JAMA 2013;309:678-88).

Nonetheless, "over the years, hydroxyethyl starch products have appeared in several resuscitation guidelines, including those of the U.S. Hospital Consortium, and have often been advocated as the cornerstone of resuscitation therapy," the researchers noted.

Many of the data supporting the use of hydroxyethyl starch were recently retracted from the literature, however, after an investigation found that leading scientist Dr. Joachim Boldt had used unethical research practices and had fabricated data in at least 88 studies.

"All major systematic reviews and clinical guidelines are now being revised to account for the retracted data and permit sensitivity analyses on the remaining publications by Boldt et al.," Dr. Zarychanski and his colleagues said.

They performed a rigorous systematic review of randomized controlled trials comparing hydroxyethyl starch against crystalloid, albumin, or gelatin IV fluids for acute fluid resuscitation in critically ill adults. The study subjects were treated in emergency or intensive care settings during 1982-2012.

The meta-analysis covered 38 trials, including 7 studies by Dr. Boldt that had not been retracted because they had been published before 1999, the cutoff date for the misconduct investigation.

A total of 35 studies involving 10,880 patients contributed mortality data to the meta-analysis. The overall mortality risk was significantly higher for patients randomly assigned to receive hydroxyethyl starch than for those assigned to other solutions (relative risk, 1.07).

When the data from the seven Dr. Boldt studies were excluded from the meta-analysis, the pooled results from the remaining 28 trials (10,290 patients) showed an even stronger increase in mortality risk (RR, 1.09).

The seven Boldt trials were then excluded from all further analyses.

Ten trials reported on the rate of renal replacement therapy in 9,258 patients. The use of hydroxyethyl starch was associated with a significantly greater risk of renal injury (RR, 1.32), compared with other resuscitation fluids.

The incidence of acute renal failure was reported in five trials involving 8,725 patients. Again, the incidence of this adverse effect was significantly greater in patients randomly assigned to receive hydroxyethyl starch than in those receiving other fluids (RR, 1.27).

Several sensitivity and subgroup analyses all supported the findings from the main analysis. The results indicate that "clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns," Dr. Zarychanski and his associates said.

Although hydroxyethyl starch solutions are effective volume expanders, their effects are not confined to the circulatory system, the investigators explained. The solutions also are deposited in the endothelial cells, kidneys, liver, muscle, skin, and spleen.

"Proponents of starch solutions have argued increased safety with each newly marketed product, but evidence from randomized trials [does] not support these claims," the study authors said.

In addition, their meta-analysis demonstrated that the publication of inaccurate or fraudulent data "can influence how the global medical community interprets a given body of literature, and how exclusion of questionable studies can shift the balance of evidence toward benefit or harm."

Dr. Zarychanski reported no relevant financial disclosures; an associate reported ties to Bristol-Myers Squibb and Abbott Laboratories.

imnews@elsevier.com

Hydroxyethyl starch, a synthetic colloid used worldwide for acute fluid resuscitation in critically ill patients, appears to significantly raise the risks of mortality and severe renal injury, compared with other resuscitation solutions, according to a systematic review and meta-analysis published in the Feb. 20 issue of JAMA.

The use of hydroxyethyl starch and other colloidal starch solutions has increased "despite their higher cost relative to crystalloid solutions, lack of evidence of their clinical superiority, and pervasive safety concerns," said Dr. Ryan Zarychanski of the section of critical care and the section of hematology and medical oncology, University of Manitoba, Winnipeg, and his associates (JAMA 2013;309:678-88).

Nonetheless, "over the years, hydroxyethyl starch products have appeared in several resuscitation guidelines, including those of the U.S. Hospital Consortium, and have often been advocated as the cornerstone of resuscitation therapy," the researchers noted.

Many of the data supporting the use of hydroxyethyl starch were recently retracted from the literature, however, after an investigation found that leading scientist Dr. Joachim Boldt had used unethical research practices and had fabricated data in at least 88 studies.

"All major systematic reviews and clinical guidelines are now being revised to account for the retracted data and permit sensitivity analyses on the remaining publications by Boldt et al.," Dr. Zarychanski and his colleagues said.

They performed a rigorous systematic review of randomized controlled trials comparing hydroxyethyl starch against crystalloid, albumin, or gelatin IV fluids for acute fluid resuscitation in critically ill adults. The study subjects were treated in emergency or intensive care settings during 1982-2012.

The meta-analysis covered 38 trials, including 7 studies by Dr. Boldt that had not been retracted because they had been published before 1999, the cutoff date for the misconduct investigation.

A total of 35 studies involving 10,880 patients contributed mortality data to the meta-analysis. The overall mortality risk was significantly higher for patients randomly assigned to receive hydroxyethyl starch than for those assigned to other solutions (relative risk, 1.07).

When the data from the seven Dr. Boldt studies were excluded from the meta-analysis, the pooled results from the remaining 28 trials (10,290 patients) showed an even stronger increase in mortality risk (RR, 1.09).

The seven Boldt trials were then excluded from all further analyses.

Ten trials reported on the rate of renal replacement therapy in 9,258 patients. The use of hydroxyethyl starch was associated with a significantly greater risk of renal injury (RR, 1.32), compared with other resuscitation fluids.

The incidence of acute renal failure was reported in five trials involving 8,725 patients. Again, the incidence of this adverse effect was significantly greater in patients randomly assigned to receive hydroxyethyl starch than in those receiving other fluids (RR, 1.27).

Several sensitivity and subgroup analyses all supported the findings from the main analysis. The results indicate that "clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns," Dr. Zarychanski and his associates said.

Although hydroxyethyl starch solutions are effective volume expanders, their effects are not confined to the circulatory system, the investigators explained. The solutions also are deposited in the endothelial cells, kidneys, liver, muscle, skin, and spleen.

"Proponents of starch solutions have argued increased safety with each newly marketed product, but evidence from randomized trials [does] not support these claims," the study authors said.

In addition, their meta-analysis demonstrated that the publication of inaccurate or fraudulent data "can influence how the global medical community interprets a given body of literature, and how exclusion of questionable studies can shift the balance of evidence toward benefit or harm."

Dr. Zarychanski reported no relevant financial disclosures; an associate reported ties to Bristol-Myers Squibb and Abbott Laboratories.

imnews@elsevier.com

Hydroxyethyl starch, a synthetic colloid used worldwide for acute fluid resuscitation in critically ill patients, appears to significantly raise the risks of mortality and severe renal injury, compared with other resuscitation solutions, according to a systematic review and meta-analysis published in the Feb. 20 issue of JAMA.

The use of hydroxyethyl starch and other colloidal starch solutions has increased "despite their higher cost relative to crystalloid solutions, lack of evidence of their clinical superiority, and pervasive safety concerns," said Dr. Ryan Zarychanski of the section of critical care and the section of hematology and medical oncology, University of Manitoba, Winnipeg, and his associates (JAMA 2013;309:678-88).

Nonetheless, "over the years, hydroxyethyl starch products have appeared in several resuscitation guidelines, including those of the U.S. Hospital Consortium, and have often been advocated as the cornerstone of resuscitation therapy," the researchers noted.

Many of the data supporting the use of hydroxyethyl starch were recently retracted from the literature, however, after an investigation found that leading scientist Dr. Joachim Boldt had used unethical research practices and had fabricated data in at least 88 studies.

"All major systematic reviews and clinical guidelines are now being revised to account for the retracted data and permit sensitivity analyses on the remaining publications by Boldt et al.," Dr. Zarychanski and his colleagues said.

They performed a rigorous systematic review of randomized controlled trials comparing hydroxyethyl starch against crystalloid, albumin, or gelatin IV fluids for acute fluid resuscitation in critically ill adults. The study subjects were treated in emergency or intensive care settings during 1982-2012.

The meta-analysis covered 38 trials, including 7 studies by Dr. Boldt that had not been retracted because they had been published before 1999, the cutoff date for the misconduct investigation.

A total of 35 studies involving 10,880 patients contributed mortality data to the meta-analysis. The overall mortality risk was significantly higher for patients randomly assigned to receive hydroxyethyl starch than for those assigned to other solutions (relative risk, 1.07).

When the data from the seven Dr. Boldt studies were excluded from the meta-analysis, the pooled results from the remaining 28 trials (10,290 patients) showed an even stronger increase in mortality risk (RR, 1.09).

The seven Boldt trials were then excluded from all further analyses.

Ten trials reported on the rate of renal replacement therapy in 9,258 patients. The use of hydroxyethyl starch was associated with a significantly greater risk of renal injury (RR, 1.32), compared with other resuscitation fluids.

The incidence of acute renal failure was reported in five trials involving 8,725 patients. Again, the incidence of this adverse effect was significantly greater in patients randomly assigned to receive hydroxyethyl starch than in those receiving other fluids (RR, 1.27).

Several sensitivity and subgroup analyses all supported the findings from the main analysis. The results indicate that "clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns," Dr. Zarychanski and his associates said.

Although hydroxyethyl starch solutions are effective volume expanders, their effects are not confined to the circulatory system, the investigators explained. The solutions also are deposited in the endothelial cells, kidneys, liver, muscle, skin, and spleen.

"Proponents of starch solutions have argued increased safety with each newly marketed product, but evidence from randomized trials [does] not support these claims," the study authors said.

In addition, their meta-analysis demonstrated that the publication of inaccurate or fraudulent data "can influence how the global medical community interprets a given body of literature, and how exclusion of questionable studies can shift the balance of evidence toward benefit or harm."

Dr. Zarychanski reported no relevant financial disclosures; an associate reported ties to Bristol-Myers Squibb and Abbott Laboratories.

imnews@elsevier.com

The use of a robotic surgical platform to perform hysterectomy for benign disease has increased substantially since its introduction and now accounts for nearly 10% of all hysterectomies nationwide, according to a report in the Feb. 20 issue of JAMA.

At hospitals across the United States where robotically assisted hysterectomy is performed, the procedure has shown notably rapid uptake: Within 3 years it accounted for more than 20% of hysterectomies, said Dr. Jason D. Wright of Columbia University, New York, and his associates.

However, robotically assisted hysterectomy is no more effective than laparoscopic hysterectomy, and it has a similar perioperative morbidity profile. But it is markedly more expensive than any other modality of hysterectomy. "Our study indicates ... the robotic procedure offers little short-term benefit and is accompanied by significantly greater costs," the investigators wrote.

Dr. Wright and his colleagues performed a population-based analysis of the diffusion of robotically assisted hysterectomy using information from the Perspective national database, which measures resource utilization and quality. They focused on 264,758 hysterectomies for benign indications done at 441 hospitals in 2007-2010.

This included 123,288 abdominal hysterectomies, 54,912 vaginal hysterectomies, 75,761 laparoscopic hysterectomies, and 10,797 robotically assisted hysterectomies.

The rate of vaginal hysterectomy declined during the study period from 21.7% of all procedures in the first quarter of 2007 to 19.8% in the first quarter of 2010. Similarly, the rate of abdominal hysterectomy declined from 53.6% to 40.1%.

In contrast, the rate of laparoscopic hysterectomy increased during that time period, from 24.3% of all procedures in the first quarter of 2007 to 30.5% in the first quarter of 2010.

The rate of robotically assisted hysterectomy increased the most, from 0.5% to 9.5%, the investigators reported (JAMA 2013;309:689-98).

They compared complication rates between laparoscopic and robotically assisted hysterectomies, and found that the unadjusted rates of overall complications were very similar, at 5.3% and 5.5%, respectively. Also similar were the rates of intraoperative complications (2.4% vs. 2.5%), surgical site complications (2.0% vs. 1.7%), medical complications (1.2% vs. 1.6%), transfusion (1.8% vs. 1.4%), reoperation (0.1% in both groups), nonroutine hospital discharge (0.3% vs. 0.2%), and hospital mortality (0% in both groups).

However, the median cost for laparoscopic hysterectomy was $6,679, compared with $8,868 for robotically assisted hysterectomy. "Even when we excluded the fixed cost of the robotic platform and examined only variable costs, we noted that robotic hysterectomy remained the most costly modality for hysterectomy," Dr. Wright and his associates wrote.

Other researchers have posited that if robotically assisted hysterectomy replaced conventional surgery, health care costs would increase by more than $2.5 billion, Dr. Wright and his colleagues added.

Findings of the current investigation "highlight the importance of developing rational strategies to implement new surgical technologies," they said.

The reasons for the rapid uptake of robotic gynecologic surgery are not yet known, but several factors likely contributed. Robotic surgery may be easier to learn than laparoscopy "because it is more analogous to traditional open surgery." Also, robotic assistance may permit surgeons to perform "more technically demanding cases that would otherwise have required laparotomy," the investigators said.

And importantly, "robotic surgery has been the subject of extensive marketing, not only to surgeons and hospitals, but also to medical consumers," Dr. Wright and his colleagues noted.

They added that their analysis was limited because the data set didn’t include several important factors that likely influenced the selection of a given surgical approach, such as the patient’s body mass index and surgical history, as well as the estimated weight of the uterus.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

The use of a robotic surgical platform to perform hysterectomy for benign disease has increased substantially since its introduction and now accounts for nearly 10% of all hysterectomies nationwide, according to a report in the Feb. 20 issue of JAMA.

At hospitals across the United States where robotically assisted hysterectomy is performed, the procedure has shown notably rapid uptake: Within 3 years it accounted for more than 20% of hysterectomies, said Dr. Jason D. Wright of Columbia University, New York, and his associates.

However, robotically assisted hysterectomy is no more effective than laparoscopic hysterectomy, and it has a similar perioperative morbidity profile. But it is markedly more expensive than any other modality of hysterectomy. "Our study indicates ... the robotic procedure offers little short-term benefit and is accompanied by significantly greater costs," the investigators wrote.

Dr. Wright and his colleagues performed a population-based analysis of the diffusion of robotically assisted hysterectomy using information from the Perspective national database, which measures resource utilization and quality. They focused on 264,758 hysterectomies for benign indications done at 441 hospitals in 2007-2010.

This included 123,288 abdominal hysterectomies, 54,912 vaginal hysterectomies, 75,761 laparoscopic hysterectomies, and 10,797 robotically assisted hysterectomies.

The rate of vaginal hysterectomy declined during the study period from 21.7% of all procedures in the first quarter of 2007 to 19.8% in the first quarter of 2010. Similarly, the rate of abdominal hysterectomy declined from 53.6% to 40.1%.

In contrast, the rate of laparoscopic hysterectomy increased during that time period, from 24.3% of all procedures in the first quarter of 2007 to 30.5% in the first quarter of 2010.

The rate of robotically assisted hysterectomy increased the most, from 0.5% to 9.5%, the investigators reported (JAMA 2013;309:689-98).

They compared complication rates between laparoscopic and robotically assisted hysterectomies, and found that the unadjusted rates of overall complications were very similar, at 5.3% and 5.5%, respectively. Also similar were the rates of intraoperative complications (2.4% vs. 2.5%), surgical site complications (2.0% vs. 1.7%), medical complications (1.2% vs. 1.6%), transfusion (1.8% vs. 1.4%), reoperation (0.1% in both groups), nonroutine hospital discharge (0.3% vs. 0.2%), and hospital mortality (0% in both groups).

However, the median cost for laparoscopic hysterectomy was $6,679, compared with $8,868 for robotically assisted hysterectomy. "Even when we excluded the fixed cost of the robotic platform and examined only variable costs, we noted that robotic hysterectomy remained the most costly modality for hysterectomy," Dr. Wright and his associates wrote.

Other researchers have posited that if robotically assisted hysterectomy replaced conventional surgery, health care costs would increase by more than $2.5 billion, Dr. Wright and his colleagues added.

Findings of the current investigation "highlight the importance of developing rational strategies to implement new surgical technologies," they said.

The reasons for the rapid uptake of robotic gynecologic surgery are not yet known, but several factors likely contributed. Robotic surgery may be easier to learn than laparoscopy "because it is more analogous to traditional open surgery." Also, robotic assistance may permit surgeons to perform "more technically demanding cases that would otherwise have required laparotomy," the investigators said.

And importantly, "robotic surgery has been the subject of extensive marketing, not only to surgeons and hospitals, but also to medical consumers," Dr. Wright and his colleagues noted.

They added that their analysis was limited because the data set didn’t include several important factors that likely influenced the selection of a given surgical approach, such as the patient’s body mass index and surgical history, as well as the estimated weight of the uterus.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

The use of a robotic surgical platform to perform hysterectomy for benign disease has increased substantially since its introduction and now accounts for nearly 10% of all hysterectomies nationwide, according to a report in the Feb. 20 issue of JAMA.

At hospitals across the United States where robotically assisted hysterectomy is performed, the procedure has shown notably rapid uptake: Within 3 years it accounted for more than 20% of hysterectomies, said Dr. Jason D. Wright of Columbia University, New York, and his associates.

However, robotically assisted hysterectomy is no more effective than laparoscopic hysterectomy, and it has a similar perioperative morbidity profile. But it is markedly more expensive than any other modality of hysterectomy. "Our study indicates ... the robotic procedure offers little short-term benefit and is accompanied by significantly greater costs," the investigators wrote.

Dr. Wright and his colleagues performed a population-based analysis of the diffusion of robotically assisted hysterectomy using information from the Perspective national database, which measures resource utilization and quality. They focused on 264,758 hysterectomies for benign indications done at 441 hospitals in 2007-2010.

This included 123,288 abdominal hysterectomies, 54,912 vaginal hysterectomies, 75,761 laparoscopic hysterectomies, and 10,797 robotically assisted hysterectomies.

The rate of vaginal hysterectomy declined during the study period from 21.7% of all procedures in the first quarter of 2007 to 19.8% in the first quarter of 2010. Similarly, the rate of abdominal hysterectomy declined from 53.6% to 40.1%.

In contrast, the rate of laparoscopic hysterectomy increased during that time period, from 24.3% of all procedures in the first quarter of 2007 to 30.5% in the first quarter of 2010.

The rate of robotically assisted hysterectomy increased the most, from 0.5% to 9.5%, the investigators reported (JAMA 2013;309:689-98).

They compared complication rates between laparoscopic and robotically assisted hysterectomies, and found that the unadjusted rates of overall complications were very similar, at 5.3% and 5.5%, respectively. Also similar were the rates of intraoperative complications (2.4% vs. 2.5%), surgical site complications (2.0% vs. 1.7%), medical complications (1.2% vs. 1.6%), transfusion (1.8% vs. 1.4%), reoperation (0.1% in both groups), nonroutine hospital discharge (0.3% vs. 0.2%), and hospital mortality (0% in both groups).

However, the median cost for laparoscopic hysterectomy was $6,679, compared with $8,868 for robotically assisted hysterectomy. "Even when we excluded the fixed cost of the robotic platform and examined only variable costs, we noted that robotic hysterectomy remained the most costly modality for hysterectomy," Dr. Wright and his associates wrote.

Other researchers have posited that if robotically assisted hysterectomy replaced conventional surgery, health care costs would increase by more than $2.5 billion, Dr. Wright and his colleagues added.

Findings of the current investigation "highlight the importance of developing rational strategies to implement new surgical technologies," they said.

The reasons for the rapid uptake of robotic gynecologic surgery are not yet known, but several factors likely contributed. Robotic surgery may be easier to learn than laparoscopy "because it is more analogous to traditional open surgery." Also, robotic assistance may permit surgeons to perform "more technically demanding cases that would otherwise have required laparotomy," the investigators said.

And importantly, "robotic surgery has been the subject of extensive marketing, not only to surgeons and hospitals, but also to medical consumers," Dr. Wright and his colleagues noted.

They added that their analysis was limited because the data set didn’t include several important factors that likely influenced the selection of a given surgical approach, such as the patient’s body mass index and surgical history, as well as the estimated weight of the uterus.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

More than 18% of smokers who were inpatients at a large urban teaching hospital reported smoking during their stay, even though smoking was prohibited in the hospital buildings, according to an online report in the Archives of Internal Medicine.

Nicotine replacement therapy at admission delayed but did not prevent these patients from smoking eventually, said Susan Regan, Ph.D., of the tobacco research and treatment center at Massachusetts General Hospital, Boston, and her associates.

Virtually all hospitals now prohibit smoking indoors, but many allow patients, as well as staff, to smoke outdoors on the hospital grounds. "The fact that patients may go outside to smoke, especially without supervision or in inclement weather, raises safety concerns," the investigators said.

It also may compromise quality of care and hospital efficiency if patients aren’t available for assessments or treatments because they’re outside smoking. And smoking during a hospitalization can delay recovery and impair wound healing. In addition, inpatients who duck outside to smoke "deprive themselves of an opportunity to initiate a quit attempt in a supportive, smoke-free environment," Dr. Regan and her colleagues said.

They studied inpatient smoking during a 3-year period at the hospital, where smoking is banned indoors and outdoors except for two outdoor shelters. The study subjects were 2,185 adult inpatients who were automatically referred to the facility’s tobacco treatment service at admission, which facilitated the ordering of nicotine replacement therapy and provided a bedside counselor to assist in managing nicotine withdrawal.

The counselor also gave brief (5 minutes or less) advice on quitting smoking, as well as longer (20 minutes) cessation counseling for patients who expressed interest in quitting. Patients’ in-hospital smoking was assessed by self-report during their hospital stays and telephone follow-up in the 2 weeks after discharge.

Median length of stay was 5 days, and 62% of the subjects received nicotine replacement therapy; one-third received the therapy on the first day of their stay. The mean patient age was 53 years, and 58% of the study subjects were men.

Overall, 18.4% of these patients reported that they smoked during their hospital stay. Patients were more likely to report such smoking if they were younger, had longer hospitalizations, and had no plans to quit.

"Patients with longer stays might require increasing nicotine dose or supplementation of patch with shorter-acting forms of nicotine replacement therapy" such as nicotine gum or lozenges, the investigators said (Arch. Intern. Med. 2012; doi:10.1001/2013.jamainternmend.300).

The number of cigarettes that subjects typically smoked was not as predictive of smoking during hospitalization as was the intensity of their cigarette cravings.

"It may be difficult to predict the intensity of cravings during an admission from preadmission smoking level, due to individual variability in response to illness and the hospital environment. Routine ongoing assessment of cigarette craving, although more time-consuming, might be a more effective means of identifying patients who will have difficulty remaining abstinent during their stay and assist in titrating nicotine dose for patients already receiving nicotine replacement therapy," Dr. Regan and her associates said.

She reported no financial conflicts.

More than 18% of smokers who were inpatients at a large urban teaching hospital reported smoking during their stay, even though smoking was prohibited in the hospital buildings, according to an online report in the Archives of Internal Medicine.

Nicotine replacement therapy at admission delayed but did not prevent these patients from smoking eventually, said Susan Regan, Ph.D., of the tobacco research and treatment center at Massachusetts General Hospital, Boston, and her associates.

Virtually all hospitals now prohibit smoking indoors, but many allow patients, as well as staff, to smoke outdoors on the hospital grounds. "The fact that patients may go outside to smoke, especially without supervision or in inclement weather, raises safety concerns," the investigators said.

It also may compromise quality of care and hospital efficiency if patients aren’t available for assessments or treatments because they’re outside smoking. And smoking during a hospitalization can delay recovery and impair wound healing. In addition, inpatients who duck outside to smoke "deprive themselves of an opportunity to initiate a quit attempt in a supportive, smoke-free environment," Dr. Regan and her colleagues said.

They studied inpatient smoking during a 3-year period at the hospital, where smoking is banned indoors and outdoors except for two outdoor shelters. The study subjects were 2,185 adult inpatients who were automatically referred to the facility’s tobacco treatment service at admission, which facilitated the ordering of nicotine replacement therapy and provided a bedside counselor to assist in managing nicotine withdrawal.

The counselor also gave brief (5 minutes or less) advice on quitting smoking, as well as longer (20 minutes) cessation counseling for patients who expressed interest in quitting. Patients’ in-hospital smoking was assessed by self-report during their hospital stays and telephone follow-up in the 2 weeks after discharge.

Median length of stay was 5 days, and 62% of the subjects received nicotine replacement therapy; one-third received the therapy on the first day of their stay. The mean patient age was 53 years, and 58% of the study subjects were men.

Overall, 18.4% of these patients reported that they smoked during their hospital stay. Patients were more likely to report such smoking if they were younger, had longer hospitalizations, and had no plans to quit.

"Patients with longer stays might require increasing nicotine dose or supplementation of patch with shorter-acting forms of nicotine replacement therapy" such as nicotine gum or lozenges, the investigators said (Arch. Intern. Med. 2012; doi:10.1001/2013.jamainternmend.300).

The number of cigarettes that subjects typically smoked was not as predictive of smoking during hospitalization as was the intensity of their cigarette cravings.

"It may be difficult to predict the intensity of cravings during an admission from preadmission smoking level, due to individual variability in response to illness and the hospital environment. Routine ongoing assessment of cigarette craving, although more time-consuming, might be a more effective means of identifying patients who will have difficulty remaining abstinent during their stay and assist in titrating nicotine dose for patients already receiving nicotine replacement therapy," Dr. Regan and her associates said.

She reported no financial conflicts.

More than 18% of smokers who were inpatients at a large urban teaching hospital reported smoking during their stay, even though smoking was prohibited in the hospital buildings, according to an online report in the Archives of Internal Medicine.

Nicotine replacement therapy at admission delayed but did not prevent these patients from smoking eventually, said Susan Regan, Ph.D., of the tobacco research and treatment center at Massachusetts General Hospital, Boston, and her associates.

Virtually all hospitals now prohibit smoking indoors, but many allow patients, as well as staff, to smoke outdoors on the hospital grounds. "The fact that patients may go outside to smoke, especially without supervision or in inclement weather, raises safety concerns," the investigators said.

It also may compromise quality of care and hospital efficiency if patients aren’t available for assessments or treatments because they’re outside smoking. And smoking during a hospitalization can delay recovery and impair wound healing. In addition, inpatients who duck outside to smoke "deprive themselves of an opportunity to initiate a quit attempt in a supportive, smoke-free environment," Dr. Regan and her colleagues said.

They studied inpatient smoking during a 3-year period at the hospital, where smoking is banned indoors and outdoors except for two outdoor shelters. The study subjects were 2,185 adult inpatients who were automatically referred to the facility’s tobacco treatment service at admission, which facilitated the ordering of nicotine replacement therapy and provided a bedside counselor to assist in managing nicotine withdrawal.

The counselor also gave brief (5 minutes or less) advice on quitting smoking, as well as longer (20 minutes) cessation counseling for patients who expressed interest in quitting. Patients’ in-hospital smoking was assessed by self-report during their hospital stays and telephone follow-up in the 2 weeks after discharge.

Median length of stay was 5 days, and 62% of the subjects received nicotine replacement therapy; one-third received the therapy on the first day of their stay. The mean patient age was 53 years, and 58% of the study subjects were men.

Overall, 18.4% of these patients reported that they smoked during their hospital stay. Patients were more likely to report such smoking if they were younger, had longer hospitalizations, and had no plans to quit.

"Patients with longer stays might require increasing nicotine dose or supplementation of patch with shorter-acting forms of nicotine replacement therapy" such as nicotine gum or lozenges, the investigators said (Arch. Intern. Med. 2012; doi:10.1001/2013.jamainternmend.300).

The number of cigarettes that subjects typically smoked was not as predictive of smoking during hospitalization as was the intensity of their cigarette cravings.

"It may be difficult to predict the intensity of cravings during an admission from preadmission smoking level, due to individual variability in response to illness and the hospital environment. Routine ongoing assessment of cigarette craving, although more time-consuming, might be a more effective means of identifying patients who will have difficulty remaining abstinent during their stay and assist in titrating nicotine dose for patients already receiving nicotine replacement therapy," Dr. Regan and her associates said.

She reported no financial conflicts.

Maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder, the most severe form of autism spectrum disorders, in the children, according to a Norwegian study reported in the Feb. 13 issue of JAMA.

"This finding does not establish a causal relation between folic acid use and autistic disorder, but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biologic mechanisms that may explain the inverse association," said Dr. Pål Surén of the Norwegian Institute of Public Health, Oslo, and his associates.

thinkstockphotos.com

Folic acid supplements during pregnancy reduce the risk of neural tube defects in the offspring, and there is some evidence that they may also reduce the risk of other neurodevelopmental disorders. A recent analysis of data from the Norwegian Mother and Child Cohort Study found that maternal use of folic acid supplements was associated with a lower risk of severe language delay in their children at age 3 years.

Dr. Surén and his colleagues used data from the same cohort study to examine a possible association between the supplements and risk of autism spectrum disorders. The Norwegian Mother and Child Cohort Study is a national registry of 109,020 children born between 1999 and 2009.

For this analysis, the researchers assessed data concerning 85,176 children in the registry. At final follow-up, the subjects ranged in age from 3.3 years to 10.2 years (mean age, 6.4 years).

A total of 270 of these children (0.32%) were diagnosed as having autism spectrum disorders: 0.13% had autistic disorder, 0.07% had Asperger’s syndrome, and 0.12% had pervasive developmental disorder not otherwise specified.

Approximately 33% of the mothers took folic acid supplements during the interval from 4 weeks before conception to 8 weeks afterward. This period was chosen for the analysis because folic acid’s effects on the developing central nervous system of the fetus are most prominent during this time. "The interval covers or precedes events of critical importance to the fetal brain, such as the closure of the neural tube 28 days after conception and the embryonic period that includes development of the basic brain structures 15-56 days after conception," the investigators noted.

They found an inverse association between the mother’s use of folic acid supplements periconceptually and the risk that the child would develop autistic disorder. Of the children whose mothers took the supplements, 0.10% developed autistic disorder, compared with 0.21% in children whose mothers did not.

The adjusted odds ratio of autistic disorder was 0.61 in children of folic acid users. Further adjusting the data to account for comorbid maternal illness and concomitant medication use did not change this OR, Dr. Surén and his associates reported (JAMA 2013;309:570-7).

Women who took folic acid supplements were more likely to have a college-level education, to have planned the pregnancy, to be nonsmokers, and to have a prepregnancy body mass index less than 25 kg/m², which are all factors that could confound the association with autism. To address this issue, the investigators assessed the use of fish oil supplements in the study sample.

Use of fish oil supplements correlated with the same parental characteristics as did use of folic acid supplements, but it did not correlate with the risk of autistic disorder, they noted.

Similarly, the inverse association for folic acid use in the periconceptual period was not evident in mothers who took the supplements only later in pregnancy.

"Our findings indicate that the inverse association may be largely driven by the children with autistic disorder and severe language delay at 35 months, who were presumably the more severely affected children," the investigators added.

This study was funded in part by the Research Council of Norway. The investigators did not report having any financial conflicts of interest.

Maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder, the most severe form of autism spectrum disorders, in the children, according to a Norwegian study reported in the Feb. 13 issue of JAMA.

"This finding does not establish a causal relation between folic acid use and autistic disorder, but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biologic mechanisms that may explain the inverse association," said Dr. Pål Surén of the Norwegian Institute of Public Health, Oslo, and his associates.

thinkstockphotos.com

Folic acid supplements during pregnancy reduce the risk of neural tube defects in the offspring, and there is some evidence that they may also reduce the risk of other neurodevelopmental disorders. A recent analysis of data from the Norwegian Mother and Child Cohort Study found that maternal use of folic acid supplements was associated with a lower risk of severe language delay in their children at age 3 years.

Dr. Surén and his colleagues used data from the same cohort study to examine a possible association between the supplements and risk of autism spectrum disorders. The Norwegian Mother and Child Cohort Study is a national registry of 109,020 children born between 1999 and 2009.

For this analysis, the researchers assessed data concerning 85,176 children in the registry. At final follow-up, the subjects ranged in age from 3.3 years to 10.2 years (mean age, 6.4 years).

A total of 270 of these children (0.32%) were diagnosed as having autism spectrum disorders: 0.13% had autistic disorder, 0.07% had Asperger’s syndrome, and 0.12% had pervasive developmental disorder not otherwise specified.

Approximately 33% of the mothers took folic acid supplements during the interval from 4 weeks before conception to 8 weeks afterward. This period was chosen for the analysis because folic acid’s effects on the developing central nervous system of the fetus are most prominent during this time. "The interval covers or precedes events of critical importance to the fetal brain, such as the closure of the neural tube 28 days after conception and the embryonic period that includes development of the basic brain structures 15-56 days after conception," the investigators noted.

They found an inverse association between the mother’s use of folic acid supplements periconceptually and the risk that the child would develop autistic disorder. Of the children whose mothers took the supplements, 0.10% developed autistic disorder, compared with 0.21% in children whose mothers did not.

The adjusted odds ratio of autistic disorder was 0.61 in children of folic acid users. Further adjusting the data to account for comorbid maternal illness and concomitant medication use did not change this OR, Dr. Surén and his associates reported (JAMA 2013;309:570-7).

Women who took folic acid supplements were more likely to have a college-level education, to have planned the pregnancy, to be nonsmokers, and to have a prepregnancy body mass index less than 25 kg/m², which are all factors that could confound the association with autism. To address this issue, the investigators assessed the use of fish oil supplements in the study sample.

Use of fish oil supplements correlated with the same parental characteristics as did use of folic acid supplements, but it did not correlate with the risk of autistic disorder, they noted.

Similarly, the inverse association for folic acid use in the periconceptual period was not evident in mothers who took the supplements only later in pregnancy.

"Our findings indicate that the inverse association may be largely driven by the children with autistic disorder and severe language delay at 35 months, who were presumably the more severely affected children," the investigators added.

This study was funded in part by the Research Council of Norway. The investigators did not report having any financial conflicts of interest.

Maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder, the most severe form of autism spectrum disorders, in the children, according to a Norwegian study reported in the Feb. 13 issue of JAMA.

"This finding does not establish a causal relation between folic acid use and autistic disorder, but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biologic mechanisms that may explain the inverse association," said Dr. Pål Surén of the Norwegian Institute of Public Health, Oslo, and his associates.

thinkstockphotos.com

Folic acid supplements during pregnancy reduce the risk of neural tube defects in the offspring, and there is some evidence that they may also reduce the risk of other neurodevelopmental disorders. A recent analysis of data from the Norwegian Mother and Child Cohort Study found that maternal use of folic acid supplements was associated with a lower risk of severe language delay in their children at age 3 years.

Dr. Surén and his colleagues used data from the same cohort study to examine a possible association between the supplements and risk of autism spectrum disorders. The Norwegian Mother and Child Cohort Study is a national registry of 109,020 children born between 1999 and 2009.

For this analysis, the researchers assessed data concerning 85,176 children in the registry. At final follow-up, the subjects ranged in age from 3.3 years to 10.2 years (mean age, 6.4 years).

A total of 270 of these children (0.32%) were diagnosed as having autism spectrum disorders: 0.13% had autistic disorder, 0.07% had Asperger’s syndrome, and 0.12% had pervasive developmental disorder not otherwise specified.

Approximately 33% of the mothers took folic acid supplements during the interval from 4 weeks before conception to 8 weeks afterward. This period was chosen for the analysis because folic acid’s effects on the developing central nervous system of the fetus are most prominent during this time. "The interval covers or precedes events of critical importance to the fetal brain, such as the closure of the neural tube 28 days after conception and the embryonic period that includes development of the basic brain structures 15-56 days after conception," the investigators noted.

They found an inverse association between the mother’s use of folic acid supplements periconceptually and the risk that the child would develop autistic disorder. Of the children whose mothers took the supplements, 0.10% developed autistic disorder, compared with 0.21% in children whose mothers did not.

The adjusted odds ratio of autistic disorder was 0.61 in children of folic acid users. Further adjusting the data to account for comorbid maternal illness and concomitant medication use did not change this OR, Dr. Surén and his associates reported (JAMA 2013;309:570-7).

Women who took folic acid supplements were more likely to have a college-level education, to have planned the pregnancy, to be nonsmokers, and to have a prepregnancy body mass index less than 25 kg/m², which are all factors that could confound the association with autism. To address this issue, the investigators assessed the use of fish oil supplements in the study sample.

Use of fish oil supplements correlated with the same parental characteristics as did use of folic acid supplements, but it did not correlate with the risk of autistic disorder, they noted.

Similarly, the inverse association for folic acid use in the periconceptual period was not evident in mothers who took the supplements only later in pregnancy.

"Our findings indicate that the inverse association may be largely driven by the children with autistic disorder and severe language delay at 35 months, who were presumably the more severely affected children," the investigators added.

This study was funded in part by the Research Council of Norway. The investigators did not report having any financial conflicts of interest.

Tedizolid, a second-generation oxazolidinone available in both oral and IV formulations, was found to be noninferior to linezolid for the treatment of acute, complicated infections of the skin and skin structure, including methicillin-resistant Staphylococcus aureus infections, according to a report in the Feb. 13 issue of JAMA.

In a phase III, randomized clinical trial, oral tedizolid phosphate (also known as TR-701) was at least as effective as oral linezolid early in the course of infection (at 48-72 hours after initiating therapy), and response to the drug persisted at a later follow-up at 7-14 days after treatment ended. Early effectiveness is important because clinicians decide whether to continue with their chosen agent or switch to different drugs during that period.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Tedizolid offers an advantage over linezolid in that it requires only once-daily dosing of a 200-mg tablet for a total of 6 days; the standard course of linezolid requires twice-daily dosing of a 600-mg tablet for 10 days. In this trial, tedizolid produced fewer gastrointestinal adverse effects and halved the rate of low platelet counts, compared with linezolid, said Dr. Philippe Prokocimer of Trius Therapeutics, San Diego, and his associates.

Trius, the maker of tedizolid, funded and conducted this 1-year, double-blind study at 54 medical centers in North America, Latin America, and Europe.

The researchers compared the two antibiotics in 667 adults (age range, 18-100 years) who had cellulitis/erysipelas, major cutaneous abscess, or wound infection surrounded by erythema, with a minimum total lesion surface of 75 cm². The study subjects also had at least one local and one regional or one systemic sign of infection, and the infecting organism was either thought to be or proven to be a gram-positive pathogen.

The subjects were stratified by the presence or absence of fever at baseline, the geographic region where they resided, and the type of infection they had, and then randomly assigned to receive tedizolid (332 patients) or linezolid (335 patients). Both groups presented a similar clinical picture, with a median infected area of 188 cm; 87% of the study population had lymphadenopathy adjacent to the lesion, 41% had abnormal white blood cell counts, and 18% were febrile.

In the primary efficacy intention-to-treat analysis, 79.5% of the subjects receiving tedizolid and 79.4% receiving linezolid were classified as responders – meaning they were afebrile and their primary skin lesions had stopped spreading – when evaluated at 48-72 hours after the first dose of the antibiotics.

Conversely, 8.1% of the subjects receiving tedizolid and 10.4% of those receiving linezolid were true nonresponders, with fever or continued spread of the primary lesion, at 48-72 hours.

Thus, tedizolid met the criteria for noninferiority to linezolid at this time point, Dr. Prokocimer and his colleagues reported (JAMA 2013;309:559-69).

The remaining subjects were classified as "indeterminate" responders, usually because temperature data were missing or were only available outside the time window specified in the study protocol.

Secondary efficacy measures, sustained treatment response rates at two later follow-up times, followed a similar pattern. At the end of treatment, 69.3% of the tedizolid group and 71.9% of the linezolid group were deemed responders, and at final follow-up 1-2 weeks later, 80.2% and 81.1% were responders, respectively.

Results of several sensitivity and subgroup analyses confirmed those of these primary and secondary analyses. "Of particular interest are the similar treatment response rates in the tedizolid group (78%) and in the linezolid group (76.1%) in the sensitivity analysis that was based on the Foundation for the National Institutes of Health recommended outcome," which is a 20% or greater reduction in the lesion area.

Also of note was the finding that response rates were similarly high (approximately 85%) with both antibiotics in the subgroup of 178 patients who had methicillin-resistant Staphylococcus aureus (MRSA) infections.

Rates of adverse events and of serious adverse events were similar between the two study groups, with fewer patients in the tedizolid group reporting GI symptoms.

Postmarketing studies have reported possible links between linezolid and myelosuppression. in this study, low platelet counts were less than half as frequent in the subjects who received tedizolid as in those who received linezolid, but the analysis "was not adequately powered to make conclusions about the risk of myelosuppression with tedizolid," the authors said.

The investigators reported ties to Trius, Cerexa, Achaogen, and other companies.

Tedizolid, a second-generation oxazolidinone available in both oral and IV formulations, was found to be noninferior to linezolid for the treatment of acute, complicated infections of the skin and skin structure, including methicillin-resistant Staphylococcus aureus infections, according to a report in the Feb. 13 issue of JAMA.

In a phase III, randomized clinical trial, oral tedizolid phosphate (also known as TR-701) was at least as effective as oral linezolid early in the course of infection (at 48-72 hours after initiating therapy), and response to the drug persisted at a later follow-up at 7-14 days after treatment ended. Early effectiveness is important because clinicians decide whether to continue with their chosen agent or switch to different drugs during that period.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Tedizolid offers an advantage over linezolid in that it requires only once-daily dosing of a 200-mg tablet for a total of 6 days; the standard course of linezolid requires twice-daily dosing of a 600-mg tablet for 10 days. In this trial, tedizolid produced fewer gastrointestinal adverse effects and halved the rate of low platelet counts, compared with linezolid, said Dr. Philippe Prokocimer of Trius Therapeutics, San Diego, and his associates.

Trius, the maker of tedizolid, funded and conducted this 1-year, double-blind study at 54 medical centers in North America, Latin America, and Europe.

The researchers compared the two antibiotics in 667 adults (age range, 18-100 years) who had cellulitis/erysipelas, major cutaneous abscess, or wound infection surrounded by erythema, with a minimum total lesion surface of 75 cm². The study subjects also had at least one local and one regional or one systemic sign of infection, and the infecting organism was either thought to be or proven to be a gram-positive pathogen.

The subjects were stratified by the presence or absence of fever at baseline, the geographic region where they resided, and the type of infection they had, and then randomly assigned to receive tedizolid (332 patients) or linezolid (335 patients). Both groups presented a similar clinical picture, with a median infected area of 188 cm; 87% of the study population had lymphadenopathy adjacent to the lesion, 41% had abnormal white blood cell counts, and 18% were febrile.

In the primary efficacy intention-to-treat analysis, 79.5% of the subjects receiving tedizolid and 79.4% receiving linezolid were classified as responders – meaning they were afebrile and their primary skin lesions had stopped spreading – when evaluated at 48-72 hours after the first dose of the antibiotics.

Conversely, 8.1% of the subjects receiving tedizolid and 10.4% of those receiving linezolid were true nonresponders, with fever or continued spread of the primary lesion, at 48-72 hours.

Thus, tedizolid met the criteria for noninferiority to linezolid at this time point, Dr. Prokocimer and his colleagues reported (JAMA 2013;309:559-69).

The remaining subjects were classified as "indeterminate" responders, usually because temperature data were missing or were only available outside the time window specified in the study protocol.

Secondary efficacy measures, sustained treatment response rates at two later follow-up times, followed a similar pattern. At the end of treatment, 69.3% of the tedizolid group and 71.9% of the linezolid group were deemed responders, and at final follow-up 1-2 weeks later, 80.2% and 81.1% were responders, respectively.

Results of several sensitivity and subgroup analyses confirmed those of these primary and secondary analyses. "Of particular interest are the similar treatment response rates in the tedizolid group (78%) and in the linezolid group (76.1%) in the sensitivity analysis that was based on the Foundation for the National Institutes of Health recommended outcome," which is a 20% or greater reduction in the lesion area.

Also of note was the finding that response rates were similarly high (approximately 85%) with both antibiotics in the subgroup of 178 patients who had methicillin-resistant Staphylococcus aureus (MRSA) infections.

Rates of adverse events and of serious adverse events were similar between the two study groups, with fewer patients in the tedizolid group reporting GI symptoms.

Postmarketing studies have reported possible links between linezolid and myelosuppression. in this study, low platelet counts were less than half as frequent in the subjects who received tedizolid as in those who received linezolid, but the analysis "was not adequately powered to make conclusions about the risk of myelosuppression with tedizolid," the authors said.

The investigators reported ties to Trius, Cerexa, Achaogen, and other companies.

Tedizolid, a second-generation oxazolidinone available in both oral and IV formulations, was found to be noninferior to linezolid for the treatment of acute, complicated infections of the skin and skin structure, including methicillin-resistant Staphylococcus aureus infections, according to a report in the Feb. 13 issue of JAMA.

In a phase III, randomized clinical trial, oral tedizolid phosphate (also known as TR-701) was at least as effective as oral linezolid early in the course of infection (at 48-72 hours after initiating therapy), and response to the drug persisted at a later follow-up at 7-14 days after treatment ended. Early effectiveness is important because clinicians decide whether to continue with their chosen agent or switch to different drugs during that period.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

Tedizolid offers an advantage over linezolid in that it requires only once-daily dosing of a 200-mg tablet for a total of 6 days; the standard course of linezolid requires twice-daily dosing of a 600-mg tablet for 10 days. In this trial, tedizolid produced fewer gastrointestinal adverse effects and halved the rate of low platelet counts, compared with linezolid, said Dr. Philippe Prokocimer of Trius Therapeutics, San Diego, and his associates.

Trius, the maker of tedizolid, funded and conducted this 1-year, double-blind study at 54 medical centers in North America, Latin America, and Europe.

The researchers compared the two antibiotics in 667 adults (age range, 18-100 years) who had cellulitis/erysipelas, major cutaneous abscess, or wound infection surrounded by erythema, with a minimum total lesion surface of 75 cm². The study subjects also had at least one local and one regional or one systemic sign of infection, and the infecting organism was either thought to be or proven to be a gram-positive pathogen.

The subjects were stratified by the presence or absence of fever at baseline, the geographic region where they resided, and the type of infection they had, and then randomly assigned to receive tedizolid (332 patients) or linezolid (335 patients). Both groups presented a similar clinical picture, with a median infected area of 188 cm; 87% of the study population had lymphadenopathy adjacent to the lesion, 41% had abnormal white blood cell counts, and 18% were febrile.

In the primary efficacy intention-to-treat analysis, 79.5% of the subjects receiving tedizolid and 79.4% receiving linezolid were classified as responders – meaning they were afebrile and their primary skin lesions had stopped spreading – when evaluated at 48-72 hours after the first dose of the antibiotics.

Conversely, 8.1% of the subjects receiving tedizolid and 10.4% of those receiving linezolid were true nonresponders, with fever or continued spread of the primary lesion, at 48-72 hours.

Thus, tedizolid met the criteria for noninferiority to linezolid at this time point, Dr. Prokocimer and his colleagues reported (JAMA 2013;309:559-69).

The remaining subjects were classified as "indeterminate" responders, usually because temperature data were missing or were only available outside the time window specified in the study protocol.

Secondary efficacy measures, sustained treatment response rates at two later follow-up times, followed a similar pattern. At the end of treatment, 69.3% of the tedizolid group and 71.9% of the linezolid group were deemed responders, and at final follow-up 1-2 weeks later, 80.2% and 81.1% were responders, respectively.

Results of several sensitivity and subgroup analyses confirmed those of these primary and secondary analyses. "Of particular interest are the similar treatment response rates in the tedizolid group (78%) and in the linezolid group (76.1%) in the sensitivity analysis that was based on the Foundation for the National Institutes of Health recommended outcome," which is a 20% or greater reduction in the lesion area.

Also of note was the finding that response rates were similarly high (approximately 85%) with both antibiotics in the subgroup of 178 patients who had methicillin-resistant Staphylococcus aureus (MRSA) infections.

Rates of adverse events and of serious adverse events were similar between the two study groups, with fewer patients in the tedizolid group reporting GI symptoms.

Postmarketing studies have reported possible links between linezolid and myelosuppression. in this study, low platelet counts were less than half as frequent in the subjects who received tedizolid as in those who received linezolid, but the analysis "was not adequately powered to make conclusions about the risk of myelosuppression with tedizolid," the authors said.

The investigators reported ties to Trius, Cerexa, Achaogen, and other companies.

Two measures for evaluating hospital performance – 30-day mortality and 30-day readmission rate – were found to be fully independent of each other in the first comprehensive examination of the relationship between the two, according to a report in the Feb. 13 issue of JAMA.

Physicians, researchers, and policy analysts have raised concerns that hospital mortality rates and readmission rates could interact with each other in such a way that would impair their accuracy as measures of a hospital’s performance.

For example, hospitals with lower mortality might be more likely to have higher readmission rates because the very interventions that improve mortality might also create a higher-risk group of discharged patients. Conversely, hospitals with higher mortality might have had patients die before they could be readmitted, so their readmission rates would be artificially lower.

If such interactions occurred, hospitals might be forced to choose one performance measure over the other, said Dr. Harlan M. Krumholz of the section of cardiovascular medicine at Yale University, New Haven, Conn. and his associates.

Alternatively, if 30-day mortality and 30-day readmission rates were found to have a positive correlation, it could be inferred that they reflect similar processes and are redundant.

Dr. Krumholz and his colleagues assessed both measures in Medicare fee-for-service beneficiaries across the United States who were hospitalized for acute MI (590,809 deaths and 586,027 readmissions), heart failure (1,161,179 deaths and 1,430,030 readmissions), or pneumonia (1,225,366 deaths and 1,297,031 readmissions) over a 3-year period.

"We failed to find evidence that a hospital’s performance on the measure for 30-day risk-standardized mortality rate is strongly associated with performance on 30-day risk-standardized readmission rate. These findings should allay concerns that institutions with good performance on [mortality measures] will necessarily be identified as poor performers on their [readmission measures]," the investigators said.

At all levels of performance on the mortality measure, "we found both high and low performers on the readmission measures," they noted (JAMA 2013;309:587-93).

Their findings were consistent across all types of hospitals, regardless of size (bed capacity), teaching status, location (urban or rural), safety-net status, or type of funding (public or private).

The study results indicate that mortality and readmission measures reflect mutually distinct processes and are therefore not redundant, Dr. Krumholz said.

The study was supported by several agencies within the U.S. Department of Health and Human Services.

Two measures for evaluating hospital performance – 30-day mortality and 30-day readmission rate – were found to be fully independent of each other in the first comprehensive examination of the relationship between the two, according to a report in the Feb. 13 issue of JAMA.

Physicians, researchers, and policy analysts have raised concerns that hospital mortality rates and readmission rates could interact with each other in such a way that would impair their accuracy as measures of a hospital’s performance.

For example, hospitals with lower mortality might be more likely to have higher readmission rates because the very interventions that improve mortality might also create a higher-risk group of discharged patients. Conversely, hospitals with higher mortality might have had patients die before they could be readmitted, so their readmission rates would be artificially lower.

If such interactions occurred, hospitals might be forced to choose one performance measure over the other, said Dr. Harlan M. Krumholz of the section of cardiovascular medicine at Yale University, New Haven, Conn. and his associates.

Alternatively, if 30-day mortality and 30-day readmission rates were found to have a positive correlation, it could be inferred that they reflect similar processes and are redundant.

Dr. Krumholz and his colleagues assessed both measures in Medicare fee-for-service beneficiaries across the United States who were hospitalized for acute MI (590,809 deaths and 586,027 readmissions), heart failure (1,161,179 deaths and 1,430,030 readmissions), or pneumonia (1,225,366 deaths and 1,297,031 readmissions) over a 3-year period.

"We failed to find evidence that a hospital’s performance on the measure for 30-day risk-standardized mortality rate is strongly associated with performance on 30-day risk-standardized readmission rate. These findings should allay concerns that institutions with good performance on [mortality measures] will necessarily be identified as poor performers on their [readmission measures]," the investigators said.

At all levels of performance on the mortality measure, "we found both high and low performers on the readmission measures," they noted (JAMA 2013;309:587-93).

Their findings were consistent across all types of hospitals, regardless of size (bed capacity), teaching status, location (urban or rural), safety-net status, or type of funding (public or private).

The study results indicate that mortality and readmission measures reflect mutually distinct processes and are therefore not redundant, Dr. Krumholz said.

The study was supported by several agencies within the U.S. Department of Health and Human Services.

Two measures for evaluating hospital performance – 30-day mortality and 30-day readmission rate – were found to be fully independent of each other in the first comprehensive examination of the relationship between the two, according to a report in the Feb. 13 issue of JAMA.

Physicians, researchers, and policy analysts have raised concerns that hospital mortality rates and readmission rates could interact with each other in such a way that would impair their accuracy as measures of a hospital’s performance.

For example, hospitals with lower mortality might be more likely to have higher readmission rates because the very interventions that improve mortality might also create a higher-risk group of discharged patients. Conversely, hospitals with higher mortality might have had patients die before they could be readmitted, so their readmission rates would be artificially lower.

If such interactions occurred, hospitals might be forced to choose one performance measure over the other, said Dr. Harlan M. Krumholz of the section of cardiovascular medicine at Yale University, New Haven, Conn. and his associates.

Alternatively, if 30-day mortality and 30-day readmission rates were found to have a positive correlation, it could be inferred that they reflect similar processes and are redundant.

Dr. Krumholz and his colleagues assessed both measures in Medicare fee-for-service beneficiaries across the United States who were hospitalized for acute MI (590,809 deaths and 586,027 readmissions), heart failure (1,161,179 deaths and 1,430,030 readmissions), or pneumonia (1,225,366 deaths and 1,297,031 readmissions) over a 3-year period.

"We failed to find evidence that a hospital’s performance on the measure for 30-day risk-standardized mortality rate is strongly associated with performance on 30-day risk-standardized readmission rate. These findings should allay concerns that institutions with good performance on [mortality measures] will necessarily be identified as poor performers on their [readmission measures]," the investigators said.

At all levels of performance on the mortality measure, "we found both high and low performers on the readmission measures," they noted (JAMA 2013;309:587-93).

Their findings were consistent across all types of hospitals, regardless of size (bed capacity), teaching status, location (urban or rural), safety-net status, or type of funding (public or private).

The study results indicate that mortality and readmission measures reflect mutually distinct processes and are therefore not redundant, Dr. Krumholz said.

The study was supported by several agencies within the U.S. Department of Health and Human Services.