Jennie Smith

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Almost 350 million adults now have diabetes, according to results from a sweeping new study evaluating 3 decades of fasting–plasma glucose trends worldwide.

The findings, published online June 25 in the Lancet (doi:10.1016/S0140-6736(11)60679-X), challenge recent estimates of the global diabetic population at about 285 million (Diabetes Res Clin Pract 2009; 87: 4-14) and also suggest, in contrast to other views, that diabetes in east and southeast Asia is rising mainly because of aging and growing populations, rather than lifestyle changes.

The increased global estimate reflects a larger number of national studies analyzed for this study, along with different analytical methods, reported members of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group, which conducted the study.

Worldwide, the mean age-standardized fasting–plasma glucose (FPG) concentrations have risen on average by 0.08 mmol/L per decade (0.07 for men and 0.09 for women) since 1980, which corresponds to an increase in overall diabetes prevalence of about 7% per decade (from 8.3% in 1980 to 9.8% in 2008 among men, and from 7.5% to 9.2% among women).

The number of people with diabetes is estimated to have more than doubled, from about 153 million in 1980 to about 347 million in 2008. Of these, 40% live in China or India.

About 70% of the worldwide increase in prevalence can be attributed to population growth and aging, the investigators wrote, but the rise in age-standardized FPG indicates "an important epidemiological component" accounting for the other 30%, although the reasons vary by region. The authors found, by comparing their results to a recent body mass index (BMI) study of similar scope (Lancet 2011;377: 557–67), that the correlation between changes in fasting glucose and changes in BMI was 0.71 for women and 0.57 for men.

In no part of the world was a significant decline in FPG noted over the study period, except among Singaporean women, although levels in many regions remained flat.

For their research, which was funded by the Bill and Melinda Gates Foundation and the World Health Organization, the investigators looked at data from all available health examination surveys and epidemiological studies, including national and regional studies, for the 29-year study period. The study covered 199 countries and territories, although 92 countries provided no population-based data.

The researchers sought information on FPG among adults aged 25 years and older, by sex. They chose mean FPG as the main glycemic measure because it is widely used in population-based studies (including more than 71% of the studies used in their analysis), and "there is a continuous association between FPG and cardiovascular disease, including at levels below clinical thresholds for diabetes diagnosis," the investigators wrote.

Data from studies using different glycemic indicators were converted to FPG for this analysis. For each sex, investigators used Bayesian modeling to estimate mean FPG and its uncertainty by age, country, and year, to adjust for whether a study was nationally, regionally, or locally representative. Diabetes prevalence was estimated using mean FPG.

The harmonization of data into a readily comparable analysis, spanning large populations over a long time period, was the main strength of this study, compared with previous studies, the investigators wrote. Its size was another: The study looked at data for 2.7 million participants over 370 country-years. An added strength was the incorporation of data from several large national studies from east and southeast Asia.

The study’s main weaknesses, they wrote, were that some countries did not provide population-based data, and that many country-years did not have data, especially in the 1980s; the authors adjusted for these gaps with modeling.

Oceania, the Caribbean regions, and North Africa and the Middle East were found to have the highest FPG and diabetes prevalence in 2008, with an age- standardized mean FPG of 6.5 mmol/L or higher in several South Pacific island nations; diabetes prevalence was estimated at 21%-25% in men and up to 32% of women.

Countries in southeast Asia, east Africa, and Andean Latin America had the lowest mean FPG in 2008 (as low as 5 mmol/L or less). Among high-income countries, mean FPG and diabetes prevalence were highest in the United States, Greenland, Malta, New Zealand, and Spain, and were lowest in the Netherlands and Austria for both sexes (and in France for women). Mean FPG in the Netherlands, Austria, and France was lower than in Japan and South Korea, despite higher BMIs.

FPG increased the most among South Pacific Islanders, by 0.22 mmol/L per decade in men and 0.32 in women. Tropical and southern Latin America and South Asia saw large increases for men, and south Asia, central Asia, north Africa, and the Middle East recorded large increases for women. FPG remained essentially flat in western Europe, increasing by 0.07 mmol/L per decade in men and by 0.03 in women. In North America, by contrast, FPG rose by 0.18 mmol/L per decade in men and by 0.14 in women.

For women in Singapore, mean FPG decreased by 0.21 mmol/L per decade during the study period, the only significant decrease recorded.

In an editorial comment accompanying the study, Dr. Martin Tobias of the Health and Disability Intelligence Department of New Zealand’s Ministry of Health, noted that the finding that 70% of the world’s diabetes increase was attributable to population growth and aging confirms "the old saying that demography explains two-thirds of everything." However, he added, the findings are "stark," both supporting the position that diabetes poses severe risks for families, nations, and the entire world, and reinforcing the need to strengthen worldwide diabetes surveillance.

Dr. Tobias defended the study’s complex statistical modeling methods to make up for lost country-years and missing data. "Readers may ask how trends can be estimated for 92 countries with no data at all, and for the first decade of the pandemic (the 1980s), for which information is sparse. We can be reassured since the Collaborating Group tested the validity of their model by deliberately removing data for some countries and years, and applied the model to this restricted dataset. The model adequately predicted values for the withheld data [that is, out-of-sample prediction], which confirms fitness for purpose," he wrote.

Two authors on the study, Christopher J. Paciorek, Ph.D., and John K. Lin, both of the Harvard School of Public Health in Boston, disclosed stock holdings with Pfizer and Johnson & Johnson, respectively. Study author Dr. Majid Ezzati acknowledged chairing a session at the World Cardiology Congress, which was supported by its organizer. Dr. Tobias declared that he had no conflicts of interest.

Intrauterine devices, or IUDs, are suitable for nearly all women, including those who have just delivered a baby, have had an abortion or miscarriage, or who have a history of ectopic pregnancy, the American College of Obstetricians and Gynecologists now says.

The ACOG’s practice bulletin covers the three long-acting reversible contraceptives currently approved by the Food and Drug Administration: the copper T380A IUD, the levonorgestrel intrauterine system, and subdermal etonogestrel implants.

The copper IUD is recommended as an effective method of emergency contraception when inserted 5 days after unprotected intercourse, ACOG now says, citing a documented pregnancy rate of 0.23% from one study investigating the method in nearly 2,000 women (BJOG 2010;117:1205-10).

Another key recommendation is that prophylaxis with antibiotics to prevent pelvic infection is not necessary before inserting an IUD. This is supported by a meta-analysis of four randomized, controlled trials of women with a low prevalence of sexually transmitted infections, which found that antibiotic prophylaxis at the time of IUD insertion did not decrease the risk of pelvic inflammatory disease or the likelihood of removal within 3 months (Cochrane Database of Systematic Reviews 2007 [doi:10.1002/14651858.CD001327]).

The ACOG bulletin is the first full update in 6 years of its recommendations on IUDs, which have gained more widespread use in the interim – from 1.3% of contraceptive use in the United States in 2002 to 5.5% in 2008. The organization’s bulletins on IUDs – which in the 1990s were marked by restrictive and cautionary language – have become progressively more positive in the past decade, as safety findings accumulate and the consensus on patient eligibility has broadened.

A bulletin from the early 1990s describes IUDs as suited for older, parous, monogamous women who are not ready for sterilization, have no history of pelvic inflammatory disease or ectopic pregnancy, and who could not take oral contraceptives (Int. J. Gynaecol. Obstet. 1993;41:189-93).

But by 2005, the last time it issued a full practice bulletin concerning IUDs (Obstet. Gynecol. 2005;105:223-32), ACOG’s tone had changed dramatically, calling the devices "safe, effective, long-term contraception [that] should be considered for all women who seek a reliable, reversible contraception that is effective before coitus." The same year, the package insert of the copper IUD was changed to include its use in women who have not had any children, and in 2007, ACOG published a committee opinion saying that IUDs could be considered appropriate for use in adolescents (Obstet. Gynecol. 2007;110:1493-5).

The current bulletin, which replaces the 2005 guidance, not only includes the postcoital, emergency contraceptive use of the copper IUD, but explicitly promotes IUDs and implants, saying that the methods "may help lower U.S. unintended pregnancy rates because gaps in use and discontinuation of shorter acting methods are associated with unintended pregnancy rates in high-risk women."

The ACOG separated its updated recommendations into three levels based on the type and quality of evidence supporting them (Practice Bulletin 121; Obstet. Gynecol. 2011;118:184-96).

The recommendations that routine antibiotic prophylaxis is unnecessary before IUD insertion and that the copper IUD may be inserted up to 5 days after intercourse to prevent unwanted pregnancy, are classified as level A, which means that they are supported by good and consistent scientific evidence, ACOG said.

Insertion of an IUD immediately after childbirth is safe, the ACOG says, although it classifies this as a level B recommendation, one based on inconsistent evidence. The risk of an IUD inserted immediately after childbirth being expelled may be as high as 24%, ACOG noted, and insertion is contraindicated immediately after childbirth for women with peripartum chorioamnionitis, endometritis, or puerperal sepsis.

Other level B recommendations now include offering IUDs to women with previous ectopic pregnancy and to women who have just miscarried or had an abortion.

The safety evidence for insertion immediately after a first trimester abortion is stronger than that for a second-trimester procedure, according to the recommendations. Evidence suggests that women who have an IUD inserted immediately after abortion have higher rates of use and lower rates of repeat abortion, compared with women who received appointments for insertion later (Contraception 2011;83:34-40). However, the recommendations state that women who have had septic abortions should not receive an IUD until at least 3 months afterward.

Women who have had an ectopic pregnancy need not be excluded from receiving IUDs as they have not been shown to increase the absolute risk of ectopic pregnancy.

Subdermal implants may be offered to non-breastfeeding women any time after childbirth.

Expert opinion supports the recommendation that implants not be offered to breastfeeding women until 4 weeks after childbirth, because of theoretical concerns about contraceptive hormones affecting infant development.

In addition, expert opinion supports offering IUDs and implants to women and adolescents who have not had a baby.

The Practice Bulletin was developed by ACOG’s Committee on Practice Bulletins. No information on potential conflicts of interest was given.

Intrauterine devices, or IUDs, are suitable for nearly all women, including those who have just delivered a baby, have had an abortion or miscarriage, or who have a history of ectopic pregnancy, the American College of Obstetricians and Gynecologists now says.

The ACOG’s practice bulletin covers the three long-acting reversible contraceptives currently approved by the Food and Drug Administration: the copper T380A IUD, the levonorgestrel intrauterine system, and subdermal etonogestrel implants.

The copper IUD is recommended as an effective method of emergency contraception when inserted 5 days after unprotected intercourse, ACOG now says, citing a documented pregnancy rate of 0.23% from one study investigating the method in nearly 2,000 women (BJOG 2010;117:1205-10).

Another key recommendation is that prophylaxis with antibiotics to prevent pelvic infection is not necessary before inserting an IUD. This is supported by a meta-analysis of four randomized, controlled trials of women with a low prevalence of sexually transmitted infections, which found that antibiotic prophylaxis at the time of IUD insertion did not decrease the risk of pelvic inflammatory disease or the likelihood of removal within 3 months (Cochrane Database of Systematic Reviews 2007 [doi:10.1002/14651858.CD001327]).

The ACOG bulletin is the first full update in 6 years of its recommendations on IUDs, which have gained more widespread use in the interim – from 1.3% of contraceptive use in the United States in 2002 to 5.5% in 2008. The organization’s bulletins on IUDs – which in the 1990s were marked by restrictive and cautionary language – have become progressively more positive in the past decade, as safety findings accumulate and the consensus on patient eligibility has broadened.

A bulletin from the early 1990s describes IUDs as suited for older, parous, monogamous women who are not ready for sterilization, have no history of pelvic inflammatory disease or ectopic pregnancy, and who could not take oral contraceptives (Int. J. Gynaecol. Obstet. 1993;41:189-93).

But by 2005, the last time it issued a full practice bulletin concerning IUDs (Obstet. Gynecol. 2005;105:223-32), ACOG’s tone had changed dramatically, calling the devices "safe, effective, long-term contraception [that] should be considered for all women who seek a reliable, reversible contraception that is effective before coitus." The same year, the package insert of the copper IUD was changed to include its use in women who have not had any children, and in 2007, ACOG published a committee opinion saying that IUDs could be considered appropriate for use in adolescents (Obstet. Gynecol. 2007;110:1493-5).

The current bulletin, which replaces the 2005 guidance, not only includes the postcoital, emergency contraceptive use of the copper IUD, but explicitly promotes IUDs and implants, saying that the methods "may help lower U.S. unintended pregnancy rates because gaps in use and discontinuation of shorter acting methods are associated with unintended pregnancy rates in high-risk women."

The ACOG separated its updated recommendations into three levels based on the type and quality of evidence supporting them (Practice Bulletin 121; Obstet. Gynecol. 2011;118:184-96).

The recommendations that routine antibiotic prophylaxis is unnecessary before IUD insertion and that the copper IUD may be inserted up to 5 days after intercourse to prevent unwanted pregnancy, are classified as level A, which means that they are supported by good and consistent scientific evidence, ACOG said.

Insertion of an IUD immediately after childbirth is safe, the ACOG says, although it classifies this as a level B recommendation, one based on inconsistent evidence. The risk of an IUD inserted immediately after childbirth being expelled may be as high as 24%, ACOG noted, and insertion is contraindicated immediately after childbirth for women with peripartum chorioamnionitis, endometritis, or puerperal sepsis.

Other level B recommendations now include offering IUDs to women with previous ectopic pregnancy and to women who have just miscarried or had an abortion.

The safety evidence for insertion immediately after a first trimester abortion is stronger than that for a second-trimester procedure, according to the recommendations. Evidence suggests that women who have an IUD inserted immediately after abortion have higher rates of use and lower rates of repeat abortion, compared with women who received appointments for insertion later (Contraception 2011;83:34-40). However, the recommendations state that women who have had septic abortions should not receive an IUD until at least 3 months afterward.

Women who have had an ectopic pregnancy need not be excluded from receiving IUDs as they have not been shown to increase the absolute risk of ectopic pregnancy.

Subdermal implants may be offered to non-breastfeeding women any time after childbirth.

Expert opinion supports the recommendation that implants not be offered to breastfeeding women until 4 weeks after childbirth, because of theoretical concerns about contraceptive hormones affecting infant development.

In addition, expert opinion supports offering IUDs and implants to women and adolescents who have not had a baby.

The Practice Bulletin was developed by ACOG’s Committee on Practice Bulletins. No information on potential conflicts of interest was given.

Intrauterine devices, or IUDs, are suitable for nearly all women, including those who have just delivered a baby, have had an abortion or miscarriage, or who have a history of ectopic pregnancy, the American College of Obstetricians and Gynecologists now says.

The ACOG’s practice bulletin covers the three long-acting reversible contraceptives currently approved by the Food and Drug Administration: the copper T380A IUD, the levonorgestrel intrauterine system, and subdermal etonogestrel implants.

The copper IUD is recommended as an effective method of emergency contraception when inserted 5 days after unprotected intercourse, ACOG now says, citing a documented pregnancy rate of 0.23% from one study investigating the method in nearly 2,000 women (BJOG 2010;117:1205-10).

Another key recommendation is that prophylaxis with antibiotics to prevent pelvic infection is not necessary before inserting an IUD. This is supported by a meta-analysis of four randomized, controlled trials of women with a low prevalence of sexually transmitted infections, which found that antibiotic prophylaxis at the time of IUD insertion did not decrease the risk of pelvic inflammatory disease or the likelihood of removal within 3 months (Cochrane Database of Systematic Reviews 2007 [doi:10.1002/14651858.CD001327]).

The ACOG bulletin is the first full update in 6 years of its recommendations on IUDs, which have gained more widespread use in the interim – from 1.3% of contraceptive use in the United States in 2002 to 5.5% in 2008. The organization’s bulletins on IUDs – which in the 1990s were marked by restrictive and cautionary language – have become progressively more positive in the past decade, as safety findings accumulate and the consensus on patient eligibility has broadened.

A bulletin from the early 1990s describes IUDs as suited for older, parous, monogamous women who are not ready for sterilization, have no history of pelvic inflammatory disease or ectopic pregnancy, and who could not take oral contraceptives (Int. J. Gynaecol. Obstet. 1993;41:189-93).

But by 2005, the last time it issued a full practice bulletin concerning IUDs (Obstet. Gynecol. 2005;105:223-32), ACOG’s tone had changed dramatically, calling the devices "safe, effective, long-term contraception [that] should be considered for all women who seek a reliable, reversible contraception that is effective before coitus." The same year, the package insert of the copper IUD was changed to include its use in women who have not had any children, and in 2007, ACOG published a committee opinion saying that IUDs could be considered appropriate for use in adolescents (Obstet. Gynecol. 2007;110:1493-5).

The current bulletin, which replaces the 2005 guidance, not only includes the postcoital, emergency contraceptive use of the copper IUD, but explicitly promotes IUDs and implants, saying that the methods "may help lower U.S. unintended pregnancy rates because gaps in use and discontinuation of shorter acting methods are associated with unintended pregnancy rates in high-risk women."

The ACOG separated its updated recommendations into three levels based on the type and quality of evidence supporting them (Practice Bulletin 121; Obstet. Gynecol. 2011;118:184-96).

The recommendations that routine antibiotic prophylaxis is unnecessary before IUD insertion and that the copper IUD may be inserted up to 5 days after intercourse to prevent unwanted pregnancy, are classified as level A, which means that they are supported by good and consistent scientific evidence, ACOG said.

Insertion of an IUD immediately after childbirth is safe, the ACOG says, although it classifies this as a level B recommendation, one based on inconsistent evidence. The risk of an IUD inserted immediately after childbirth being expelled may be as high as 24%, ACOG noted, and insertion is contraindicated immediately after childbirth for women with peripartum chorioamnionitis, endometritis, or puerperal sepsis.

Other level B recommendations now include offering IUDs to women with previous ectopic pregnancy and to women who have just miscarried or had an abortion.

The safety evidence for insertion immediately after a first trimester abortion is stronger than that for a second-trimester procedure, according to the recommendations. Evidence suggests that women who have an IUD inserted immediately after abortion have higher rates of use and lower rates of repeat abortion, compared with women who received appointments for insertion later (Contraception 2011;83:34-40). However, the recommendations state that women who have had septic abortions should not receive an IUD until at least 3 months afterward.

Women who have had an ectopic pregnancy need not be excluded from receiving IUDs as they have not been shown to increase the absolute risk of ectopic pregnancy.

Subdermal implants may be offered to non-breastfeeding women any time after childbirth.

Expert opinion supports the recommendation that implants not be offered to breastfeeding women until 4 weeks after childbirth, because of theoretical concerns about contraceptive hormones affecting infant development.

In addition, expert opinion supports offering IUDs and implants to women and adolescents who have not had a baby.

The Practice Bulletin was developed by ACOG’s Committee on Practice Bulletins. No information on potential conflicts of interest was given.

A randomized, double-blind study comparing two commercially available botulinum toxin type A injections found abobotulinumtoxinA to be more effective than onabotulinumtoxinA for treating crow's feet.

The study, published online in the Archives of Facial Plastic Surgery (doi:10.1001/archfacial.2011.37), compared the effectiveness of abobotulinumtoxinA, marketed as Dysport, with onabotulinumtoxinA, marketed as Botox, in 90 patients with lateral orbital rhytids.

Investigator and patient assessments of Merz scale scores (a visual tool used to grade wrinkles on a severity scale of 0 to 4) before and at several points after treatment were collected; the primary endpoint was investigator assessment of maximal contraction 30 days post treatment. However, patients also were asked to assess results using the same scale.

AbobotulinumtoxinA was reported by both patients and investigators to be significantly more effective in reducing lines during maximum facial contraction.

Dr. Corey S. Maas of the department of otolaryngology–head and neck surgery at the University of California, San Francisco, who is in private practice, and his colleagues enrolled 90 patients between 31 and 78 years old (mean age 54.5 years) without previous surgery or facial injections for at least 6 months; 13 were men.

All were injected with 10 U of onabotulinumtoxinA on one side of the face and 30 U of abobotulinumtoxinA on the other, according to a 1:3 ratio employed in earlier studies and judged by the principal investigator to be the best comparative dose. The study investigators were blinded as to which side of the face received which treatment, as were patients. Treatments were prepared by a nonblinded nurse.

At baseline, investigators assessed patients as having mean Merz scale scores of 3.68 on the onabotulinumtoxinA-treated sides of their faces at maximal contraction; after treatment, this became 2.33. With abobotulinumtoxinA, investigators assessed patients as having a mean score of 3.64 at baseline and 2.60 after treatment, offering a statistically significant advantage to abobotulinumtoxinA.

Patients, using the same scale, assessed more improvement on the abobotulinumtoxinA side than on the onabotulinumtoxinA side at maximal contraction and favored results from the abobotulinumtoxinA sides 67% of the time.

No statistically significant difference was seen between the two treatments when the lateral orbital rhytids were at rest.

The study was the first to evaluate both products simultaneously in a patient; crow's feet were designated as the candidate wrinkles because of the minimal likelihood of the products diffusing from one side of the face to the other, the investigators wrote.

The investigators offered no explanation for why abobotulinumtoxinA appeared to work better, but wrote in their analysis that because the main pharmacologic difference between the two medications is the hemagglutinin and non-hemagglutinin surrounding each protein, "one may theorize that these differences in efficacy can be ascribed to the hemagglutinin and non-hemagglutinin binding."

Dr. Maas disclosed that he is a consultant for and owns stock in both Medicis Aesthetics (makers of abobotulinumtoxinA) and Allergan (makers of onabotulinumtoxinA). Medicis Aesthetics funded the study.

A randomized, double-blind study comparing two commercially available botulinum toxin type A injections found abobotulinumtoxinA to be more effective than onabotulinumtoxinA for treating crow's feet.

The study, published online in the Archives of Facial Plastic Surgery (doi:10.1001/archfacial.2011.37), compared the effectiveness of abobotulinumtoxinA, marketed as Dysport, with onabotulinumtoxinA, marketed as Botox, in 90 patients with lateral orbital rhytids.

Investigator and patient assessments of Merz scale scores (a visual tool used to grade wrinkles on a severity scale of 0 to 4) before and at several points after treatment were collected; the primary endpoint was investigator assessment of maximal contraction 30 days post treatment. However, patients also were asked to assess results using the same scale.

AbobotulinumtoxinA was reported by both patients and investigators to be significantly more effective in reducing lines during maximum facial contraction.

Dr. Corey S. Maas of the department of otolaryngology–head and neck surgery at the University of California, San Francisco, who is in private practice, and his colleagues enrolled 90 patients between 31 and 78 years old (mean age 54.5 years) without previous surgery or facial injections for at least 6 months; 13 were men.

All were injected with 10 U of onabotulinumtoxinA on one side of the face and 30 U of abobotulinumtoxinA on the other, according to a 1:3 ratio employed in earlier studies and judged by the principal investigator to be the best comparative dose. The study investigators were blinded as to which side of the face received which treatment, as were patients. Treatments were prepared by a nonblinded nurse.

At baseline, investigators assessed patients as having mean Merz scale scores of 3.68 on the onabotulinumtoxinA-treated sides of their faces at maximal contraction; after treatment, this became 2.33. With abobotulinumtoxinA, investigators assessed patients as having a mean score of 3.64 at baseline and 2.60 after treatment, offering a statistically significant advantage to abobotulinumtoxinA.

Patients, using the same scale, assessed more improvement on the abobotulinumtoxinA side than on the onabotulinumtoxinA side at maximal contraction and favored results from the abobotulinumtoxinA sides 67% of the time.

No statistically significant difference was seen between the two treatments when the lateral orbital rhytids were at rest.

The study was the first to evaluate both products simultaneously in a patient; crow's feet were designated as the candidate wrinkles because of the minimal likelihood of the products diffusing from one side of the face to the other, the investigators wrote.

The investigators offered no explanation for why abobotulinumtoxinA appeared to work better, but wrote in their analysis that because the main pharmacologic difference between the two medications is the hemagglutinin and non-hemagglutinin surrounding each protein, "one may theorize that these differences in efficacy can be ascribed to the hemagglutinin and non-hemagglutinin binding."

Dr. Maas disclosed that he is a consultant for and owns stock in both Medicis Aesthetics (makers of abobotulinumtoxinA) and Allergan (makers of onabotulinumtoxinA). Medicis Aesthetics funded the study.

A randomized, double-blind study comparing two commercially available botulinum toxin type A injections found abobotulinumtoxinA to be more effective than onabotulinumtoxinA for treating crow's feet.

The study, published online in the Archives of Facial Plastic Surgery (doi:10.1001/archfacial.2011.37), compared the effectiveness of abobotulinumtoxinA, marketed as Dysport, with onabotulinumtoxinA, marketed as Botox, in 90 patients with lateral orbital rhytids.

Investigator and patient assessments of Merz scale scores (a visual tool used to grade wrinkles on a severity scale of 0 to 4) before and at several points after treatment were collected; the primary endpoint was investigator assessment of maximal contraction 30 days post treatment. However, patients also were asked to assess results using the same scale.

AbobotulinumtoxinA was reported by both patients and investigators to be significantly more effective in reducing lines during maximum facial contraction.

Dr. Corey S. Maas of the department of otolaryngology–head and neck surgery at the University of California, San Francisco, who is in private practice, and his colleagues enrolled 90 patients between 31 and 78 years old (mean age 54.5 years) without previous surgery or facial injections for at least 6 months; 13 were men.

All were injected with 10 U of onabotulinumtoxinA on one side of the face and 30 U of abobotulinumtoxinA on the other, according to a 1:3 ratio employed in earlier studies and judged by the principal investigator to be the best comparative dose. The study investigators were blinded as to which side of the face received which treatment, as were patients. Treatments were prepared by a nonblinded nurse.

At baseline, investigators assessed patients as having mean Merz scale scores of 3.68 on the onabotulinumtoxinA-treated sides of their faces at maximal contraction; after treatment, this became 2.33. With abobotulinumtoxinA, investigators assessed patients as having a mean score of 3.64 at baseline and 2.60 after treatment, offering a statistically significant advantage to abobotulinumtoxinA.

Patients, using the same scale, assessed more improvement on the abobotulinumtoxinA side than on the onabotulinumtoxinA side at maximal contraction and favored results from the abobotulinumtoxinA sides 67% of the time.

No statistically significant difference was seen between the two treatments when the lateral orbital rhytids were at rest.

The study was the first to evaluate both products simultaneously in a patient; crow's feet were designated as the candidate wrinkles because of the minimal likelihood of the products diffusing from one side of the face to the other, the investigators wrote.

The investigators offered no explanation for why abobotulinumtoxinA appeared to work better, but wrote in their analysis that because the main pharmacologic difference between the two medications is the hemagglutinin and non-hemagglutinin surrounding each protein, "one may theorize that these differences in efficacy can be ascribed to the hemagglutinin and non-hemagglutinin binding."

Dr. Maas disclosed that he is a consultant for and owns stock in both Medicis Aesthetics (makers of abobotulinumtoxinA) and Allergan (makers of onabotulinumtoxinA). Medicis Aesthetics funded the study.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton's and her colleagues' study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton's and her colleagues' study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton's and her colleagues' study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of school-based vaccination program, Australian researchers have found.

The population-based study, published online June 16 in the Lancet, examined data from a cervical-screening program in Victoria, Australia’s second largest state (Lancet 2011;377:2085-92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, Australia, which collects data on more than 99% of cervical cytology on the state’s girls and women, led the research. Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger. Older age groups saw no declines.

Vaccination records were not linked to screening data in Dr. Brotherton’s and her colleagues’ study. However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; some younger girls, however, are screened at the discretion of practitioners.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, "reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls."

The study also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women older than age 18 years. Only women younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the U.S. Centers for Disease Control and Prevention, urged care in interpreting the findings, saying that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will take much more data and several decades to establish.

"The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect," Dr. Saraiya and Dr. Hariri wrote. "However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria."

The findings may have been affected, they argued, by health care providers’ screening and managing vaccinated patients less aggressively, "especially girls younger than the recommended screening age of 18 years."

Also, "with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18-20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high." However, the study found no decrease in this age group.

The investigators acknowledged that the population-based study design was a weakness, and that further studies linking vaccination and cytology data would be needed to confirm the findings. However, they wrote, "we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease." HPV types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

Dr. Brotherton and two of her coauthors on the study acknowledged that they are investigators on an Australian Research Council linkage grant, for which CSL Biotherapies, a vaccine producer, is a partner organization. Dr. Brotherton was an investigator on an HPV prevalence study that received funding from CSL and GlaxoSmithKline.

Dr. Saraiya and Dr. Hariri declared that they had no conflicts of interest.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German officials produced the first bacteriologic evidence of enterohemorrhagic Escherchia coli contamination in bean sprouts over the weekend, adding weight to their epidemiologic findings pointing to one grower in Lower Saxony as the outbreak’s source.

Raw sprouts taken from a household in the state of North Rhine-Westphalia were found to be contaminated with the shiga toxin–producing EHEC strain O104:H4, Germany’s Federal Institute for Risk Assessment announced in a statement June 11.

The package, from the same farm in Lower Saxony that investigators suspect is the source of the outbreak, had already been opened when it was tested and members of the household were by then already ill, investigators acknowledged, making the discovery less than a smoking gun. Though there were reports of the strain being identified at the suspect farm itself, these reports had not been confirmed by German health authorities as of June 13.

On June 13 the European Center for Disease Prevention and Control reported an additional 240 cases and five EHEC deaths in Germany since Friday, though the rate of newly reported infections has slowed from previous weeks.

Altogether in Europe 3,325 cases of EHEC O104:H4 infection have been identified since May, the ECDC reported, and 817 of these have developed hemolytic uremic syndrome, a severe complication that can cause kidney damage. The outbreak death count is now 36 for Europe, with all but one death occurring in Germany.

The German news magazine Der Spiegel reported June 13 that German health officials believe at least 100 Germans will require a kidney transplant or lifetime dialysis to treat permanent damage related to hemolytic uremic syndrome caused by the outbreak.

German health authorities are pointing once again to raw sprouts as the likeliest source of an ongoing outbreak of Enterohemorrhagic E. coli, or EHEC, which has to date caused 31 confirmed deaths and more than 3,000 cases in the European Union, the vast majority of them in Germany.

Epidemiologists at the German government’s Robert Koch Institute in Berlin acknowledged that samples from a sprout farm suspected earlier this week to be the source had turned up negative for the EHEC strain. But the outbreak pattern corresponds to the sprouts being the culprit, investigators said.

In a German-language statement issued June 10, the institute urged restaurants and households not to buy bean or seed sprouts, which they said their epidemiological investigations had determined nonetheless to be the likeliest source of the outbreak, now in its sixth week of cases. The Institute also lifted its earlier recommendations concerning lettuce, tomatoes and cucumbers, saying they need no longer be avoided.

Over the past several weeks, the Koch Institute has conducted a number of analyses and case-control studies trying to identify the infection source, with nearly all of the suspicion on vegetables.

On June 10, RKI reported results from an analysis of a 112-person cohort of five groups that had eaten at a single restaurant, which revealed an 8.6-fold higher risk of EHEC illness for subjects who had consumed sprouts. Investigators had conducted extensive interviews with diners and kitchen workers, and even consulted photographs from groups taken while dining at the restaurant. A day earlier, the institute released results from a case study in which less than a third of sickened patients reported having eaten sprouts.

The institute also said that its mathematical modeling had revealed that despite a number of new EHEC and hemolytic uremic syndrome (HUS) cases, a declining trend was now observable, but that it did now know whether this was due to avoidance of raw vegetables or the drying up of the infection source.

Also June 10, the European Center for Disease Prevention and Control, in collaboration with the European Food Safety Authority, issued a technical report on E. coli in the European Union with a special focus on shigatoxin-producing EC O104, the strain responsible for the current outbreak.

Data on STEC O104 "is very scarce as this is a very rare serogroup in humans in Europe and the entire world," the report noted, with only 27 cases reported between 1987 and the onset of the current outbreak. For all but one of these cases, which pointed to milk, the precise source of infection was unknown, and four of the cases were preceded by foreign travel to Central Asia, Turkey, and North Africa.

In recent days the German health authorities have come under criticism for what has been considered a belated and disjointed response to the outbreak, which began in early May but was not reported to the ECDC for more than two weeks afterward. State health authorities in Germany have faced particular scrutiny for announcing likely infection sources, including cucumbers imported from Spain, without bacteriological evidence, resulting in Germany’s response being condemned in the European Parliament.

More recently the ECDC itself has come under criticism for its own low profile during the outbreak. "Coordination of the German public health response seems to have been utterly absent," wrote editors for the Lancet in a June 10 editorial (doi:10.1016/S0140-6736(11)60846-5). "But one should also ask: where was the [ECDC]?"

Set up in 2005, the ECDC’s role is to work "in close collaboration with the Member States and the [European] Commission to promote the necessary coherence in the risk communication process on health threats," the Lancet editors wrote. "From the public's point of view, no visible collaboration seems to have taken place."

ECDC has provided the case definition used in the outbreak and has published daily updates on laboratory confirmed cases and deaths for the E.U. as a whole.

In an e-mail interview, a spokeswoman for ECDC described the agency’s response to the outbreak as having "closely monitored the outbreak since it was first reported by the German authorities" May 22, and "supporting the activities being led by the Germany authorities given the EU dimension of this outbreak. Specifically, an ECDC expert was seconded to [the Koch Institute] on 1 June to act as a liaison and to support activities, such as ongoing epidemiological surveillance and verifying the results, and contributing to the ongoing investigations to speed up the identification of the source of the outbreak."

The ECDC has also sent its chief scientist heading of its food and waterborne disease program to Germany June 5 "to get an overview of the situation and support existing German activities," the spokeswoman said.

German health authorities are pointing once again to raw sprouts as the likeliest source of an ongoing outbreak of Enterohemorrhagic E. coli, or EHEC, which has to date caused 31 confirmed deaths and more than 3,000 cases in the European Union, the vast majority of them in Germany.

Epidemiologists at the German government’s Robert Koch Institute in Berlin acknowledged that samples from a sprout farm suspected earlier this week to be the source had turned up negative for the EHEC strain. But the outbreak pattern corresponds to the sprouts being the culprit, investigators said.

In a German-language statement issued June 10, the institute urged restaurants and households not to buy bean or seed sprouts, which they said their epidemiological investigations had determined nonetheless to be the likeliest source of the outbreak, now in its sixth week of cases. The Institute also lifted its earlier recommendations concerning lettuce, tomatoes and cucumbers, saying they need no longer be avoided.

Over the past several weeks, the Koch Institute has conducted a number of analyses and case-control studies trying to identify the infection source, with nearly all of the suspicion on vegetables.

On June 10, RKI reported results from an analysis of a 112-person cohort of five groups that had eaten at a single restaurant, which revealed an 8.6-fold higher risk of EHEC illness for subjects who had consumed sprouts. Investigators had conducted extensive interviews with diners and kitchen workers, and even consulted photographs from groups taken while dining at the restaurant. A day earlier, the institute released results from a case study in which less than a third of sickened patients reported having eaten sprouts.

The institute also said that its mathematical modeling had revealed that despite a number of new EHEC and hemolytic uremic syndrome (HUS) cases, a declining trend was now observable, but that it did now know whether this was due to avoidance of raw vegetables or the drying up of the infection source.

Also June 10, the European Center for Disease Prevention and Control, in collaboration with the European Food Safety Authority, issued a technical report on E. coli in the European Union with a special focus on shigatoxin-producing EC O104, the strain responsible for the current outbreak.

Data on STEC O104 "is very scarce as this is a very rare serogroup in humans in Europe and the entire world," the report noted, with only 27 cases reported between 1987 and the onset of the current outbreak. For all but one of these cases, which pointed to milk, the precise source of infection was unknown, and four of the cases were preceded by foreign travel to Central Asia, Turkey, and North Africa.

In recent days the German health authorities have come under criticism for what has been considered a belated and disjointed response to the outbreak, which began in early May but was not reported to the ECDC for more than two weeks afterward. State health authorities in Germany have faced particular scrutiny for announcing likely infection sources, including cucumbers imported from Spain, without bacteriological evidence, resulting in Germany’s response being condemned in the European Parliament.

More recently the ECDC itself has come under criticism for its own low profile during the outbreak. "Coordination of the German public health response seems to have been utterly absent," wrote editors for the Lancet in a June 10 editorial (doi:10.1016/S0140-6736(11)60846-5). "But one should also ask: where was the [ECDC]?"

Set up in 2005, the ECDC’s role is to work "in close collaboration with the Member States and the [European] Commission to promote the necessary coherence in the risk communication process on health threats," the Lancet editors wrote. "From the public's point of view, no visible collaboration seems to have taken place."

ECDC has provided the case definition used in the outbreak and has published daily updates on laboratory confirmed cases and deaths for the E.U. as a whole.

In an e-mail interview, a spokeswoman for ECDC described the agency’s response to the outbreak as having "closely monitored the outbreak since it was first reported by the German authorities" May 22, and "supporting the activities being led by the Germany authorities given the EU dimension of this outbreak. Specifically, an ECDC expert was seconded to [the Koch Institute] on 1 June to act as a liaison and to support activities, such as ongoing epidemiological surveillance and verifying the results, and contributing to the ongoing investigations to speed up the identification of the source of the outbreak."

The ECDC has also sent its chief scientist heading of its food and waterborne disease program to Germany June 5 "to get an overview of the situation and support existing German activities," the spokeswoman said.

German health authorities are pointing once again to raw sprouts as the likeliest source of an ongoing outbreak of Enterohemorrhagic E. coli, or EHEC, which has to date caused 31 confirmed deaths and more than 3,000 cases in the European Union, the vast majority of them in Germany.

Epidemiologists at the German government’s Robert Koch Institute in Berlin acknowledged that samples from a sprout farm suspected earlier this week to be the source had turned up negative for the EHEC strain. But the outbreak pattern corresponds to the sprouts being the culprit, investigators said.

In a German-language statement issued June 10, the institute urged restaurants and households not to buy bean or seed sprouts, which they said their epidemiological investigations had determined nonetheless to be the likeliest source of the outbreak, now in its sixth week of cases. The Institute also lifted its earlier recommendations concerning lettuce, tomatoes and cucumbers, saying they need no longer be avoided.

Over the past several weeks, the Koch Institute has conducted a number of analyses and case-control studies trying to identify the infection source, with nearly all of the suspicion on vegetables.

On June 10, RKI reported results from an analysis of a 112-person cohort of five groups that had eaten at a single restaurant, which revealed an 8.6-fold higher risk of EHEC illness for subjects who had consumed sprouts. Investigators had conducted extensive interviews with diners and kitchen workers, and even consulted photographs from groups taken while dining at the restaurant. A day earlier, the institute released results from a case study in which less than a third of sickened patients reported having eaten sprouts.

The institute also said that its mathematical modeling had revealed that despite a number of new EHEC and hemolytic uremic syndrome (HUS) cases, a declining trend was now observable, but that it did now know whether this was due to avoidance of raw vegetables or the drying up of the infection source.

Also June 10, the European Center for Disease Prevention and Control, in collaboration with the European Food Safety Authority, issued a technical report on E. coli in the European Union with a special focus on shigatoxin-producing EC O104, the strain responsible for the current outbreak.

Data on STEC O104 "is very scarce as this is a very rare serogroup in humans in Europe and the entire world," the report noted, with only 27 cases reported between 1987 and the onset of the current outbreak. For all but one of these cases, which pointed to milk, the precise source of infection was unknown, and four of the cases were preceded by foreign travel to Central Asia, Turkey, and North Africa.

In recent days the German health authorities have come under criticism for what has been considered a belated and disjointed response to the outbreak, which began in early May but was not reported to the ECDC for more than two weeks afterward. State health authorities in Germany have faced particular scrutiny for announcing likely infection sources, including cucumbers imported from Spain, without bacteriological evidence, resulting in Germany’s response being condemned in the European Parliament.

More recently the ECDC itself has come under criticism for its own low profile during the outbreak. "Coordination of the German public health response seems to have been utterly absent," wrote editors for the Lancet in a June 10 editorial (doi:10.1016/S0140-6736(11)60846-5). "But one should also ask: where was the [ECDC]?"

Set up in 2005, the ECDC’s role is to work "in close collaboration with the Member States and the [European] Commission to promote the necessary coherence in the risk communication process on health threats," the Lancet editors wrote. "From the public's point of view, no visible collaboration seems to have taken place."

ECDC has provided the case definition used in the outbreak and has published daily updates on laboratory confirmed cases and deaths for the E.U. as a whole.

In an e-mail interview, a spokeswoman for ECDC described the agency’s response to the outbreak as having "closely monitored the outbreak since it was first reported by the German authorities" May 22, and "supporting the activities being led by the Germany authorities given the EU dimension of this outbreak. Specifically, an ECDC expert was seconded to [the Koch Institute] on 1 June to act as a liaison and to support activities, such as ongoing epidemiological surveillance and verifying the results, and contributing to the ongoing investigations to speed up the identification of the source of the outbreak."

The ECDC has also sent its chief scientist heading of its food and waterborne disease program to Germany June 5 "to get an overview of the situation and support existing German activities," the spokeswoman said.