Miriam E. Tucker

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization's criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

“Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered,” said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:[Suppl. 2]:S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks' gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would “substantially increase the frequency of hyperglycemic disorders in pregnancy,” compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a “two-step” method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour “loading” test at 24-28 weeks' gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

“There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes and it would lead to a significant increase in health care costs,” the ACOG authors noted, adding “Significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes.”

ACOG and other organizations are looking ahead to the National Institutes of Health's Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. “Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM,” the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Dr. Morkrid had no financial disclosures.

View on the News

Changing Criteria Is Tough

The diagnostic criteria for gestational diabetes have been disputed for decades. We are forced to think more of those now that women from certain countries are more obese and are having their first children later in life. With diagnostic criteria, you first have to think about what you “win” by designating over 200% more women as having diabetes, investing in seeing them on a regular basis, deciding whether to treat this marginally increased glycemia, and determining what will be the outcome for these women and for their children, as well as the perinatal consequences, including delivery complications. I think you need to study all of this before you can decide to change the criteria.

It's similar to the recent decision to use hemoglobin A_1c criteria to diagnose diabetes, another controversial area. It's one thing to look simply at the increased risk with elevated HbA_1c. But from a political standpoint, HbA_1c tests are best done in the West, and are more expensive. Would we have two standards, one for the West and one for Africa? That's very difficult to sell. Also, does it apply to all forms of diabetes? No. And also, how do you convince the politicians that it's a big epidemic, when they could respond that the reason the numbers are so large is that the diagnostic criteria were changed?

Changing criteria is tough, and it has to be done based on evidence.

MICHAELA DIAMANT, M.D., is associate professor of endocrinology and scientific director of the diabetes center at Free University Medical Center, Amsterdam. She had no relevant financial disclosures.

Vitals

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization's criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

“Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered,” said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:[Suppl. 2]:S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks' gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would “substantially increase the frequency of hyperglycemic disorders in pregnancy,” compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a “two-step” method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour “loading” test at 24-28 weeks' gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

“There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes and it would lead to a significant increase in health care costs,” the ACOG authors noted, adding “Significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes.”

ACOG and other organizations are looking ahead to the National Institutes of Health's Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. “Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM,” the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Dr. Morkrid had no financial disclosures.

View on the News

Changing Criteria Is Tough

The diagnostic criteria for gestational diabetes have been disputed for decades. We are forced to think more of those now that women from certain countries are more obese and are having their first children later in life. With diagnostic criteria, you first have to think about what you “win” by designating over 200% more women as having diabetes, investing in seeing them on a regular basis, deciding whether to treat this marginally increased glycemia, and determining what will be the outcome for these women and for their children, as well as the perinatal consequences, including delivery complications. I think you need to study all of this before you can decide to change the criteria.

It's similar to the recent decision to use hemoglobin A_1c criteria to diagnose diabetes, another controversial area. It's one thing to look simply at the increased risk with elevated HbA_1c. But from a political standpoint, HbA_1c tests are best done in the West, and are more expensive. Would we have two standards, one for the West and one for Africa? That's very difficult to sell. Also, does it apply to all forms of diabetes? No. And also, how do you convince the politicians that it's a big epidemic, when they could respond that the reason the numbers are so large is that the diagnostic criteria were changed?

Changing criteria is tough, and it has to be done based on evidence.

MICHAELA DIAMANT, M.D., is associate professor of endocrinology and scientific director of the diabetes center at Free University Medical Center, Amsterdam. She had no relevant financial disclosures.

Vitals

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization's criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

“Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered,” said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:[Suppl. 2]:S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks' gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would “substantially increase the frequency of hyperglycemic disorders in pregnancy,” compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a “two-step” method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour “loading” test at 24-28 weeks' gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

“There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes and it would lead to a significant increase in health care costs,” the ACOG authors noted, adding “Significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes.”

ACOG and other organizations are looking ahead to the National Institutes of Health's Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. “Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM,” the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Dr. Morkrid had no financial disclosures.

View on the News

Changing Criteria Is Tough

The diagnostic criteria for gestational diabetes have been disputed for decades. We are forced to think more of those now that women from certain countries are more obese and are having their first children later in life. With diagnostic criteria, you first have to think about what you “win” by designating over 200% more women as having diabetes, investing in seeing them on a regular basis, deciding whether to treat this marginally increased glycemia, and determining what will be the outcome for these women and for their children, as well as the perinatal consequences, including delivery complications. I think you need to study all of this before you can decide to change the criteria.

It's similar to the recent decision to use hemoglobin A_1c criteria to diagnose diabetes, another controversial area. It's one thing to look simply at the increased risk with elevated HbA_1c. But from a political standpoint, HbA_1c tests are best done in the West, and are more expensive. Would we have two standards, one for the West and one for Africa? That's very difficult to sell. Also, does it apply to all forms of diabetes? No. And also, how do you convince the politicians that it's a big epidemic, when they could respond that the reason the numbers are so large is that the diagnostic criteria were changed?

Changing criteria is tough, and it has to be done based on evidence.

MICHAELA DIAMANT, M.D., is associate professor of endocrinology and scientific director of the diabetes center at Free University Medical Center, Amsterdam. She had no relevant financial disclosures.

Vitals

There are substantial gaps in the evidence supporting the effectiveness of influenza vaccines, particularly in the elderly, according to the findings of large systematic review and meta-analysis published online Oct. 25 in the Lancet Infectious Diseases.

Although the published report highlights the dearth of strong and consistent efficacy and effectiveness data for influenza vaccine in studies that met very strict criteria, it should not be interpreted as a suggestion to stop vaccinating, according Michael T. Osterholm, Ph.D, the study’s lead author and director of the center for infectious disease research and policy at the University of Minnesota, Minneapolis.

Dr. Osterholm said his intent in conducting and publishing this analysis was not to cast doubt on current influenza immunization efforts, but rather to influence the pace of new vaccine development.

"There is a major barrier to entry right now for venture capital and start-up companies to bring new novel technologies forward. When you have a vaccine that’s universally recommended, said by public health to be effective, and is quite cheap, why would anybody spend a billion dollars to try to make a new vaccine that’s going to be much more expensive?"

Of a total 5,707 studies published from 1967 through Feb. 15, 2011, just 31 (17 randomized and 14 observational studies) met a list of strict criteria, the most salient being the use of influenza confirmed by culture or real-time polymerase chain reaction as an outcome (Lancet Infect. Dis. 2011 Oct. 25 [doi:10.1016/S1473-3099(11)70295-X]).

"Efficacy" was defined as the reduction in influenza risk assessed from randomized clinical trials, whereas vaccine "effectiveness" was determined in observational, "real-world" trials. Studies using serology end points to diagnose influenza were excluded because of limitations that were first identified more than 50 years ago: Increased antibody titers following vaccination with an inactivated vaccine make it difficult to document a fourfold rise in hemagglutinin antibodies necessary to confirm an influenza infection, thereby leading to a high number of false negatives. Nonetheless, a large number of published studies on the inactivated vaccine continue to rely on serology as an end point, the authors pointed out.

The analysis included studies of both the trivalent inactivated vaccine (TIV) and the live attenuated (intranasal) influenza vaccine (LAIV). Among the 10 randomized, controlled trials of TIV over 12 influenza seasons, analyses for 8 of the seasons showed significant efficacy, whereas 4 did not. Of eight studies that were conducted in healthy adults aged 18-64 years over a total of nine flu seasons, the pooled efficacy was 59%. One study conducted in children aged 6-24 months over two flu seasons produced dramatically different efficacy results: 66% in the first year, –7% in the next (JAMA 2003;290:1608-16). The "minus" essentially means zero, rather than suggesting an increased risk from the vaccine, Dr. Osterholm said in the interview.

No randomized, controlled trials met the criteria for children aged 2-17 years, or for adults aged 65 years and older. Indeed, conducting placebo-controlled trials in adults aged 65 and older would be considered unethical because influenza vaccine has been recommended for that age group since 1960, the authors noted.

The picture for LAIV was different: Of the 10 randomized controlled trials assessing LAIV efficacy during 12 flu seasons, 9 showed significant efficacy. All of these were done in healthy individuals. In children aged 6 months to 7 years, there were six studies covering eight influenza seasons. The vaccine was effective in all eight, with a pooled efficacy of 83%.

But LAIV data in other age groups were less impressive. One study of LAIV in adults aged 60 and older showed significant overall efficacy (42%), but – oddly – efficacy was lower in those aged 60-69 years and higher in those aged 70 and older (Vaccine 2009;28:228-34).

Of three randomized, controlled trials of LAIV in adults aged 18-49, none showed significant protection, and no such trials met the inclusion criteria for children aged 8-17 years, Dr. Osterholm and his associates reported.

Vaccine effectiveness varied in the nine observational trials of seasonal flu vaccine, with 6 of 17 embedded analyses showing significant protection against medically-attended, laboratory-confirmed influenza. The proportion of patients receiving TIV or LAIV was not explicitly stated for these studies, but based on the age and licensed use, most estimates were for TIV. Of the five observational studies that assessed effectiveness of the 2009 pandemic H1N1 vaccine, median efficacy was 69% (range, 60%-93%).

Except for the LAIV studies in children aged 7 years or younger, the data showed substantial variability by influenza season and by age group. In some influenza seasons, the level of protection was low or not evident. In contrast to the 70%-90% overall effectiveness that is often cited for the vaccine in seasons when the vaccine is well matched to circulating strains, "we noted this magnitude of effectiveness only for LAIV use in children aged 7 or younger," Dr. Osterholm and his associates wrote.

Dr. Osterholm said that despite recent advances in vaccine research, he would like to see the pace of those efforts accelerate. "We clearly need to support efforts to bring us new novel vaccine antigens that have a much wider breadth of protection, a much longer reach in protection in terms of time, and across the variety of populations. Since influenza vaccine is now recommended for everyone, such studies would need comparison groups that receive licensed vaccines and are powered to show superiority rather than non-inferiority."

"The bottom line is we have to recognize we need these vaccines and we need them now. If this paper does anything, it’s a clarion call that we need to really fast-forward our novel influenza vaccine program forward, and quickly," Dr. Osterholm said. "But in the meantime, we should maintain public support for the present vaccines that are the best intervention available for seasonal influenza."

The analysis, funded by the Alfred P. Sloan Foundation, is part of a much larger CIDRAP report on influenza vaccine that is due out later this year.

Dr. Osterholm stated that neither he nor his coauthors have any financial disclosures.

There are substantial gaps in the evidence supporting the effectiveness of influenza vaccines, particularly in the elderly, according to the findings of large systematic review and meta-analysis published online Oct. 25 in the Lancet Infectious Diseases.

Although the published report highlights the dearth of strong and consistent efficacy and effectiveness data for influenza vaccine in studies that met very strict criteria, it should not be interpreted as a suggestion to stop vaccinating, according Michael T. Osterholm, Ph.D, the study’s lead author and director of the center for infectious disease research and policy at the University of Minnesota, Minneapolis.

Dr. Osterholm said his intent in conducting and publishing this analysis was not to cast doubt on current influenza immunization efforts, but rather to influence the pace of new vaccine development.

"There is a major barrier to entry right now for venture capital and start-up companies to bring new novel technologies forward. When you have a vaccine that’s universally recommended, said by public health to be effective, and is quite cheap, why would anybody spend a billion dollars to try to make a new vaccine that’s going to be much more expensive?"

Of a total 5,707 studies published from 1967 through Feb. 15, 2011, just 31 (17 randomized and 14 observational studies) met a list of strict criteria, the most salient being the use of influenza confirmed by culture or real-time polymerase chain reaction as an outcome (Lancet Infect. Dis. 2011 Oct. 25 [doi:10.1016/S1473-3099(11)70295-X]).

"Efficacy" was defined as the reduction in influenza risk assessed from randomized clinical trials, whereas vaccine "effectiveness" was determined in observational, "real-world" trials. Studies using serology end points to diagnose influenza were excluded because of limitations that were first identified more than 50 years ago: Increased antibody titers following vaccination with an inactivated vaccine make it difficult to document a fourfold rise in hemagglutinin antibodies necessary to confirm an influenza infection, thereby leading to a high number of false negatives. Nonetheless, a large number of published studies on the inactivated vaccine continue to rely on serology as an end point, the authors pointed out.

The analysis included studies of both the trivalent inactivated vaccine (TIV) and the live attenuated (intranasal) influenza vaccine (LAIV). Among the 10 randomized, controlled trials of TIV over 12 influenza seasons, analyses for 8 of the seasons showed significant efficacy, whereas 4 did not. Of eight studies that were conducted in healthy adults aged 18-64 years over a total of nine flu seasons, the pooled efficacy was 59%. One study conducted in children aged 6-24 months over two flu seasons produced dramatically different efficacy results: 66% in the first year, –7% in the next (JAMA 2003;290:1608-16). The "minus" essentially means zero, rather than suggesting an increased risk from the vaccine, Dr. Osterholm said in the interview.

No randomized, controlled trials met the criteria for children aged 2-17 years, or for adults aged 65 years and older. Indeed, conducting placebo-controlled trials in adults aged 65 and older would be considered unethical because influenza vaccine has been recommended for that age group since 1960, the authors noted.

The picture for LAIV was different: Of the 10 randomized controlled trials assessing LAIV efficacy during 12 flu seasons, 9 showed significant efficacy. All of these were done in healthy individuals. In children aged 6 months to 7 years, there were six studies covering eight influenza seasons. The vaccine was effective in all eight, with a pooled efficacy of 83%.

But LAIV data in other age groups were less impressive. One study of LAIV in adults aged 60 and older showed significant overall efficacy (42%), but – oddly – efficacy was lower in those aged 60-69 years and higher in those aged 70 and older (Vaccine 2009;28:228-34).

Of three randomized, controlled trials of LAIV in adults aged 18-49, none showed significant protection, and no such trials met the inclusion criteria for children aged 8-17 years, Dr. Osterholm and his associates reported.

Vaccine effectiveness varied in the nine observational trials of seasonal flu vaccine, with 6 of 17 embedded analyses showing significant protection against medically-attended, laboratory-confirmed influenza. The proportion of patients receiving TIV or LAIV was not explicitly stated for these studies, but based on the age and licensed use, most estimates were for TIV. Of the five observational studies that assessed effectiveness of the 2009 pandemic H1N1 vaccine, median efficacy was 69% (range, 60%-93%).

Except for the LAIV studies in children aged 7 years or younger, the data showed substantial variability by influenza season and by age group. In some influenza seasons, the level of protection was low or not evident. In contrast to the 70%-90% overall effectiveness that is often cited for the vaccine in seasons when the vaccine is well matched to circulating strains, "we noted this magnitude of effectiveness only for LAIV use in children aged 7 or younger," Dr. Osterholm and his associates wrote.

Dr. Osterholm said that despite recent advances in vaccine research, he would like to see the pace of those efforts accelerate. "We clearly need to support efforts to bring us new novel vaccine antigens that have a much wider breadth of protection, a much longer reach in protection in terms of time, and across the variety of populations. Since influenza vaccine is now recommended for everyone, such studies would need comparison groups that receive licensed vaccines and are powered to show superiority rather than non-inferiority."

"The bottom line is we have to recognize we need these vaccines and we need them now. If this paper does anything, it’s a clarion call that we need to really fast-forward our novel influenza vaccine program forward, and quickly," Dr. Osterholm said. "But in the meantime, we should maintain public support for the present vaccines that are the best intervention available for seasonal influenza."

The analysis, funded by the Alfred P. Sloan Foundation, is part of a much larger CIDRAP report on influenza vaccine that is due out later this year.

Dr. Osterholm stated that neither he nor his coauthors have any financial disclosures.

There are substantial gaps in the evidence supporting the effectiveness of influenza vaccines, particularly in the elderly, according to the findings of large systematic review and meta-analysis published online Oct. 25 in the Lancet Infectious Diseases.

Although the published report highlights the dearth of strong and consistent efficacy and effectiveness data for influenza vaccine in studies that met very strict criteria, it should not be interpreted as a suggestion to stop vaccinating, according Michael T. Osterholm, Ph.D, the study’s lead author and director of the center for infectious disease research and policy at the University of Minnesota, Minneapolis.

Dr. Osterholm said his intent in conducting and publishing this analysis was not to cast doubt on current influenza immunization efforts, but rather to influence the pace of new vaccine development.

"There is a major barrier to entry right now for venture capital and start-up companies to bring new novel technologies forward. When you have a vaccine that’s universally recommended, said by public health to be effective, and is quite cheap, why would anybody spend a billion dollars to try to make a new vaccine that’s going to be much more expensive?"

Of a total 5,707 studies published from 1967 through Feb. 15, 2011, just 31 (17 randomized and 14 observational studies) met a list of strict criteria, the most salient being the use of influenza confirmed by culture or real-time polymerase chain reaction as an outcome (Lancet Infect. Dis. 2011 Oct. 25 [doi:10.1016/S1473-3099(11)70295-X]).

"Efficacy" was defined as the reduction in influenza risk assessed from randomized clinical trials, whereas vaccine "effectiveness" was determined in observational, "real-world" trials. Studies using serology end points to diagnose influenza were excluded because of limitations that were first identified more than 50 years ago: Increased antibody titers following vaccination with an inactivated vaccine make it difficult to document a fourfold rise in hemagglutinin antibodies necessary to confirm an influenza infection, thereby leading to a high number of false negatives. Nonetheless, a large number of published studies on the inactivated vaccine continue to rely on serology as an end point, the authors pointed out.

The analysis included studies of both the trivalent inactivated vaccine (TIV) and the live attenuated (intranasal) influenza vaccine (LAIV). Among the 10 randomized, controlled trials of TIV over 12 influenza seasons, analyses for 8 of the seasons showed significant efficacy, whereas 4 did not. Of eight studies that were conducted in healthy adults aged 18-64 years over a total of nine flu seasons, the pooled efficacy was 59%. One study conducted in children aged 6-24 months over two flu seasons produced dramatically different efficacy results: 66% in the first year, –7% in the next (JAMA 2003;290:1608-16). The "minus" essentially means zero, rather than suggesting an increased risk from the vaccine, Dr. Osterholm said in the interview.

No randomized, controlled trials met the criteria for children aged 2-17 years, or for adults aged 65 years and older. Indeed, conducting placebo-controlled trials in adults aged 65 and older would be considered unethical because influenza vaccine has been recommended for that age group since 1960, the authors noted.

The picture for LAIV was different: Of the 10 randomized controlled trials assessing LAIV efficacy during 12 flu seasons, 9 showed significant efficacy. All of these were done in healthy individuals. In children aged 6 months to 7 years, there were six studies covering eight influenza seasons. The vaccine was effective in all eight, with a pooled efficacy of 83%.

But LAIV data in other age groups were less impressive. One study of LAIV in adults aged 60 and older showed significant overall efficacy (42%), but – oddly – efficacy was lower in those aged 60-69 years and higher in those aged 70 and older (Vaccine 2009;28:228-34).

Of three randomized, controlled trials of LAIV in adults aged 18-49, none showed significant protection, and no such trials met the inclusion criteria for children aged 8-17 years, Dr. Osterholm and his associates reported.

Vaccine effectiveness varied in the nine observational trials of seasonal flu vaccine, with 6 of 17 embedded analyses showing significant protection against medically-attended, laboratory-confirmed influenza. The proportion of patients receiving TIV or LAIV was not explicitly stated for these studies, but based on the age and licensed use, most estimates were for TIV. Of the five observational studies that assessed effectiveness of the 2009 pandemic H1N1 vaccine, median efficacy was 69% (range, 60%-93%).

Except for the LAIV studies in children aged 7 years or younger, the data showed substantial variability by influenza season and by age group. In some influenza seasons, the level of protection was low or not evident. In contrast to the 70%-90% overall effectiveness that is often cited for the vaccine in seasons when the vaccine is well matched to circulating strains, "we noted this magnitude of effectiveness only for LAIV use in children aged 7 or younger," Dr. Osterholm and his associates wrote.

Dr. Osterholm said that despite recent advances in vaccine research, he would like to see the pace of those efforts accelerate. "We clearly need to support efforts to bring us new novel vaccine antigens that have a much wider breadth of protection, a much longer reach in protection in terms of time, and across the variety of populations. Since influenza vaccine is now recommended for everyone, such studies would need comparison groups that receive licensed vaccines and are powered to show superiority rather than non-inferiority."

"The bottom line is we have to recognize we need these vaccines and we need them now. If this paper does anything, it’s a clarion call that we need to really fast-forward our novel influenza vaccine program forward, and quickly," Dr. Osterholm said. "But in the meantime, we should maintain public support for the present vaccines that are the best intervention available for seasonal influenza."

The analysis, funded by the Alfred P. Sloan Foundation, is part of a much larger CIDRAP report on influenza vaccine that is due out later this year.

Dr. Osterholm stated that neither he nor his coauthors have any financial disclosures.

10/28/11: UPDATE - This story has been revised and updated with additional information.

ATLANTA – Boys aged 11-12 years routinely should be given the quadrivalent human papillomavirus vaccine, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended.

The recommendation for boys aged 11-12 years to receive three doses of the vaccine is identical to the one currently in place for girls, except that it does not mention the other, bivalent HPV vaccine, which is not licensed for males. The vote was unanimous with one abstention, despite concerns voiced by several committee members about cost-effectiveness of the vaccine’s use in males. The vaccine becomes less cost-effective in males the more its coverage among females increases, the CDC’s Dr. Lauri Markowitz said.

The American Academy of Pediatrics Committee on Infectious Disease had previously voted for the same recommendation, Dr. Michael T. Brady, the AAP liaison to ACIP, said in an interview. The American Academy of Family Practice is expected to endorse it as well, said Dr. James Loehr, the AAFP liaison. The vote “made sense, and could possibly help with vaccination of females since now there won’t be a gender difference,” he noted.

Although routine vaccination of girls aged 11-12 years has been shown to be cost-effective in most scenarios, there is more uncertainty in cost-effectiveness estimates in women and in males. Routine HPV vaccination of boys at age 12 years could be cost-effective, particularly when female coverage is less than 50%. Those estimates range from $24,000 to $62,000 per quality-adjusted life-year (QALY) in published studies. In 2010, coverage rates in females were 49% for one dose and 32% for all three doses, Dr. Markowitz reported.

First-year costs of giving the vaccine to boys aged 11-12 years is estimated at $136,000,000, assuming an 11% probability of initiating the series and a 70% probability of completing it – somewhat lower than the uptake seen in females – at a cost of $119/dose, she said.

Some committee members voiced concern about whether cost-effectiveness estimates for males would become less favorable if vaccination rates increase in females beginning in 2012, when the proportion of girls who receive all three HPV vaccine doses by their 13th birthday will be a HEDIS (Healthcare Effectiveness Data and Information Set) measure.

Estimated costs per QALY also differed between calculations that included only diseases for which the vaccine is indicated (cervical disease, vulvar/vaginal disease, genital warts, and anal cancer) and those that also included prevention of other HPV-related conditions for which the vaccine isn’t indicated, including recurrent respiratory papillomatosis, oropharyngeal cancer, and penile cancer.

In all, most of the cost-effectiveness benefit obtained from routinely giving the vaccine to boys aged 11-12 years came from the prevention of cervical cancer in female partners, and prevention of oropharyngeal cancer in both males and females, Dr. Markowitz said.

The committee also recommended the vaccine’s use for catch-up in males aged 13-21 years who have not been previously vaccinated or who have not completed the three-dose series. Males aged 22-26 years also “may be vaccinated.” This vote was split, 8-5, with several members expressing concern that this recommendation is not harmonized with the uniform recommendation for females aged 9-26 years. Again, the different age cutoff was chosen due to cost-effectiveness considerations. However, the committee did vote to recommend the vaccine for males through age 26 years who have sex with other males and for those who are HIV-infected. For all males who have sex with males, the vaccine is cost-effective at less than $50,000/QALY.

In a joint interview, Dr. Brady and Dr. Loehr both commented that the relatively recent inclusion of cost-effectiveness considerations in the making of vaccine policy is a major shift from the past and now often overshadows other relevant information.

“It’s a huge concern, and it’s something the ACIP is wrestling with, how to incorporate cost-effectiveness data into decision-making. … I’m not sure there’s been clear guidance as to how the cost-effectiveness data is supposed to be applied,” said Dr. Loehr of Cayuga Family Medicine, Ithaca, N.Y.

Indeed, Dr. Brady pointed out that many older vaccines, such as those that prevent polio and Haemophilus influenzae type B, are cost saving because they prevent more costs than they actually cost. But, the licensure of the pneumococcal conjugate vaccine in 2000 began the shift. “As soon as Prevnar came, that changed the thought process. … Now there is cost, and the question is whether it’s a cost we feel is reasonable.”

“A lot of people believe that ACIP should only determine if something is appropriate and someone else should be responsible for the cost issues, because these are scientists, not economists,” said Dr. Brady, chair of the department of pediatrics, Ohio State University, Columbus.

Dr. Loehr noted that although the ACIP’s charter lists cost effectiveness as just one of several considerations for making vaccine recommendations, it was the main subject of discussion and questions from committee members surrounding the HPV recommendation for males. “It really does get people hung up.”

Dr. Brady and Dr. Loehr both stated that they have no financial disclosures. As a CDC employee, Dr. Markowitz has no conflicts of interest.

10/28/11: UPDATE - This story has been revised and updated with additional information.

ATLANTA – Boys aged 11-12 years routinely should be given the quadrivalent human papillomavirus vaccine, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended.

The recommendation for boys aged 11-12 years to receive three doses of the vaccine is identical to the one currently in place for girls, except that it does not mention the other, bivalent HPV vaccine, which is not licensed for males. The vote was unanimous with one abstention, despite concerns voiced by several committee members about cost-effectiveness of the vaccine’s use in males. The vaccine becomes less cost-effective in males the more its coverage among females increases, the CDC’s Dr. Lauri Markowitz said.

The American Academy of Pediatrics Committee on Infectious Disease had previously voted for the same recommendation, Dr. Michael T. Brady, the AAP liaison to ACIP, said in an interview. The American Academy of Family Practice is expected to endorse it as well, said Dr. James Loehr, the AAFP liaison. The vote “made sense, and could possibly help with vaccination of females since now there won’t be a gender difference,” he noted.

Although routine vaccination of girls aged 11-12 years has been shown to be cost-effective in most scenarios, there is more uncertainty in cost-effectiveness estimates in women and in males. Routine HPV vaccination of boys at age 12 years could be cost-effective, particularly when female coverage is less than 50%. Those estimates range from $24,000 to $62,000 per quality-adjusted life-year (QALY) in published studies. In 2010, coverage rates in females were 49% for one dose and 32% for all three doses, Dr. Markowitz reported.

First-year costs of giving the vaccine to boys aged 11-12 years is estimated at $136,000,000, assuming an 11% probability of initiating the series and a 70% probability of completing it – somewhat lower than the uptake seen in females – at a cost of $119/dose, she said.

Some committee members voiced concern about whether cost-effectiveness estimates for males would become less favorable if vaccination rates increase in females beginning in 2012, when the proportion of girls who receive all three HPV vaccine doses by their 13th birthday will be a HEDIS (Healthcare Effectiveness Data and Information Set) measure.

Estimated costs per QALY also differed between calculations that included only diseases for which the vaccine is indicated (cervical disease, vulvar/vaginal disease, genital warts, and anal cancer) and those that also included prevention of other HPV-related conditions for which the vaccine isn’t indicated, including recurrent respiratory papillomatosis, oropharyngeal cancer, and penile cancer.

In all, most of the cost-effectiveness benefit obtained from routinely giving the vaccine to boys aged 11-12 years came from the prevention of cervical cancer in female partners, and prevention of oropharyngeal cancer in both males and females, Dr. Markowitz said.

The committee also recommended the vaccine’s use for catch-up in males aged 13-21 years who have not been previously vaccinated or who have not completed the three-dose series. Males aged 22-26 years also “may be vaccinated.” This vote was split, 8-5, with several members expressing concern that this recommendation is not harmonized with the uniform recommendation for females aged 9-26 years. Again, the different age cutoff was chosen due to cost-effectiveness considerations. However, the committee did vote to recommend the vaccine for males through age 26 years who have sex with other males and for those who are HIV-infected. For all males who have sex with males, the vaccine is cost-effective at less than $50,000/QALY.

In a joint interview, Dr. Brady and Dr. Loehr both commented that the relatively recent inclusion of cost-effectiveness considerations in the making of vaccine policy is a major shift from the past and now often overshadows other relevant information.

“It’s a huge concern, and it’s something the ACIP is wrestling with, how to incorporate cost-effectiveness data into decision-making. … I’m not sure there’s been clear guidance as to how the cost-effectiveness data is supposed to be applied,” said Dr. Loehr of Cayuga Family Medicine, Ithaca, N.Y.

Indeed, Dr. Brady pointed out that many older vaccines, such as those that prevent polio and Haemophilus influenzae type B, are cost saving because they prevent more costs than they actually cost. But, the licensure of the pneumococcal conjugate vaccine in 2000 began the shift. “As soon as Prevnar came, that changed the thought process. … Now there is cost, and the question is whether it’s a cost we feel is reasonable.”

“A lot of people believe that ACIP should only determine if something is appropriate and someone else should be responsible for the cost issues, because these are scientists, not economists,” said Dr. Brady, chair of the department of pediatrics, Ohio State University, Columbus.

Dr. Loehr noted that although the ACIP’s charter lists cost effectiveness as just one of several considerations for making vaccine recommendations, it was the main subject of discussion and questions from committee members surrounding the HPV recommendation for males. “It really does get people hung up.”

Dr. Brady and Dr. Loehr both stated that they have no financial disclosures. As a CDC employee, Dr. Markowitz has no conflicts of interest.

10/28/11: UPDATE - This story has been revised and updated with additional information.

ATLANTA – Boys aged 11-12 years routinely should be given the quadrivalent human papillomavirus vaccine, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended.

The recommendation for boys aged 11-12 years to receive three doses of the vaccine is identical to the one currently in place for girls, except that it does not mention the other, bivalent HPV vaccine, which is not licensed for males. The vote was unanimous with one abstention, despite concerns voiced by several committee members about cost-effectiveness of the vaccine’s use in males. The vaccine becomes less cost-effective in males the more its coverage among females increases, the CDC’s Dr. Lauri Markowitz said.

The American Academy of Pediatrics Committee on Infectious Disease had previously voted for the same recommendation, Dr. Michael T. Brady, the AAP liaison to ACIP, said in an interview. The American Academy of Family Practice is expected to endorse it as well, said Dr. James Loehr, the AAFP liaison. The vote “made sense, and could possibly help with vaccination of females since now there won’t be a gender difference,” he noted.

Although routine vaccination of girls aged 11-12 years has been shown to be cost-effective in most scenarios, there is more uncertainty in cost-effectiveness estimates in women and in males. Routine HPV vaccination of boys at age 12 years could be cost-effective, particularly when female coverage is less than 50%. Those estimates range from $24,000 to $62,000 per quality-adjusted life-year (QALY) in published studies. In 2010, coverage rates in females were 49% for one dose and 32% for all three doses, Dr. Markowitz reported.

First-year costs of giving the vaccine to boys aged 11-12 years is estimated at $136,000,000, assuming an 11% probability of initiating the series and a 70% probability of completing it – somewhat lower than the uptake seen in females – at a cost of $119/dose, she said.

Some committee members voiced concern about whether cost-effectiveness estimates for males would become less favorable if vaccination rates increase in females beginning in 2012, when the proportion of girls who receive all three HPV vaccine doses by their 13th birthday will be a HEDIS (Healthcare Effectiveness Data and Information Set) measure.

Estimated costs per QALY also differed between calculations that included only diseases for which the vaccine is indicated (cervical disease, vulvar/vaginal disease, genital warts, and anal cancer) and those that also included prevention of other HPV-related conditions for which the vaccine isn’t indicated, including recurrent respiratory papillomatosis, oropharyngeal cancer, and penile cancer.

In all, most of the cost-effectiveness benefit obtained from routinely giving the vaccine to boys aged 11-12 years came from the prevention of cervical cancer in female partners, and prevention of oropharyngeal cancer in both males and females, Dr. Markowitz said.

The committee also recommended the vaccine’s use for catch-up in males aged 13-21 years who have not been previously vaccinated or who have not completed the three-dose series. Males aged 22-26 years also “may be vaccinated.” This vote was split, 8-5, with several members expressing concern that this recommendation is not harmonized with the uniform recommendation for females aged 9-26 years. Again, the different age cutoff was chosen due to cost-effectiveness considerations. However, the committee did vote to recommend the vaccine for males through age 26 years who have sex with other males and for those who are HIV-infected. For all males who have sex with males, the vaccine is cost-effective at less than $50,000/QALY.

In a joint interview, Dr. Brady and Dr. Loehr both commented that the relatively recent inclusion of cost-effectiveness considerations in the making of vaccine policy is a major shift from the past and now often overshadows other relevant information.

“It’s a huge concern, and it’s something the ACIP is wrestling with, how to incorporate cost-effectiveness data into decision-making. … I’m not sure there’s been clear guidance as to how the cost-effectiveness data is supposed to be applied,” said Dr. Loehr of Cayuga Family Medicine, Ithaca, N.Y.

Indeed, Dr. Brady pointed out that many older vaccines, such as those that prevent polio and Haemophilus influenzae type B, are cost saving because they prevent more costs than they actually cost. But, the licensure of the pneumococcal conjugate vaccine in 2000 began the shift. “As soon as Prevnar came, that changed the thought process. … Now there is cost, and the question is whether it’s a cost we feel is reasonable.”

“A lot of people believe that ACIP should only determine if something is appropriate and someone else should be responsible for the cost issues, because these are scientists, not economists,” said Dr. Brady, chair of the department of pediatrics, Ohio State University, Columbus.

Dr. Loehr noted that although the ACIP’s charter lists cost effectiveness as just one of several considerations for making vaccine recommendations, it was the main subject of discussion and questions from committee members surrounding the HPV recommendation for males. “It really does get people hung up.”

Dr. Brady and Dr. Loehr both stated that they have no financial disclosures. As a CDC employee, Dr. Markowitz has no conflicts of interest.

Melanoma was diagnosed in more than 45,000 people annually in the United States during 2004-2006, with a rate of 19 per 100,000 people.

That statistic, from two population-based cancer registries covering 78% of the U.S. population for those years, was among the melanoma data published in a series of articles in a special supplement to the November issue of the Journal of the American Academy of Dermatology (2011;65:S1-S156).

Among other significant findings were the following:

• Melanoma mortality accounted for $3.5 billion in lost productivity each year, with approximately $2.4 billion for men (average, $441,903 per man) and $1.2 billion for women (average, $401,046 per woman). Those who died from melanoma did so 20 years prematurely, compared with 17 years from other cancers, reported Donatus Ekwueme, Ph.D., of the Centers for Disease Control and Prevention.

• Melanoma rates were higher among white women aged 50 years and younger, Hispanic women aged 50 and younger, and Asian Pacific Islander women aged 40 and younger, compared with their male counterparts. Hispanics, American Indians/Alaska Natives, and Asians were diagnosed with melanoma at younger ages than were whites and blacks, according to analysis from Dr. Xiao-Cheng Wu of the school of public health at Louisiana State University in New Orleans.

• In 2005, 34% of adults reported having been sunburned in the past year, compared with 69% of adolescents, David Buller, Ph.D., of Klein Buendel Inc., a research firm, said in a report that also addressed the prevalence of sunburn, sun protection, and indoor-tanning behaviors.

• Fully 50% of dermatologists were unaware that they are required by state law to report their diagnosed cases of melanoma to their state central cancer registry, based on a survey of more than 400 dermatologists at a medical meeting. A slightly higher percentage (56%) do not actively report their melanoma diagnoses to a registry, according to the findings of the survey conducted by Dr. Todd Cartee of Emory University, Atlanta.

Other topics addressed include recent cutaneous melanoma trends and death rates, disease incidence in specific racial and ethnic populations as well as in adolescents and young adults, and associations between melanoma incidence and solar ultraviolet exposure and socioeconomic indicators. Also included are data on melanoma mortality and survival, sun-related behaviors such as tanning and sunscreen use, and rates of reporting.

The authors mentioned above declared no relevant conflicts of interest; the supplement was supported by the CDC.

Melanoma was diagnosed in more than 45,000 people annually in the United States during 2004-2006, with a rate of 19 per 100,000 people.

That statistic, from two population-based cancer registries covering 78% of the U.S. population for those years, was among the melanoma data published in a series of articles in a special supplement to the November issue of the Journal of the American Academy of Dermatology (2011;65:S1-S156).

Among other significant findings were the following:

• Melanoma mortality accounted for $3.5 billion in lost productivity each year, with approximately $2.4 billion for men (average, $441,903 per man) and $1.2 billion for women (average, $401,046 per woman). Those who died from melanoma did so 20 years prematurely, compared with 17 years from other cancers, reported Donatus Ekwueme, Ph.D., of the Centers for Disease Control and Prevention.

• Melanoma rates were higher among white women aged 50 years and younger, Hispanic women aged 50 and younger, and Asian Pacific Islander women aged 40 and younger, compared with their male counterparts. Hispanics, American Indians/Alaska Natives, and Asians were diagnosed with melanoma at younger ages than were whites and blacks, according to analysis from Dr. Xiao-Cheng Wu of the school of public health at Louisiana State University in New Orleans.

• In 2005, 34% of adults reported having been sunburned in the past year, compared with 69% of adolescents, David Buller, Ph.D., of Klein Buendel Inc., a research firm, said in a report that also addressed the prevalence of sunburn, sun protection, and indoor-tanning behaviors.

• Fully 50% of dermatologists were unaware that they are required by state law to report their diagnosed cases of melanoma to their state central cancer registry, based on a survey of more than 400 dermatologists at a medical meeting. A slightly higher percentage (56%) do not actively report their melanoma diagnoses to a registry, according to the findings of the survey conducted by Dr. Todd Cartee of Emory University, Atlanta.

Other topics addressed include recent cutaneous melanoma trends and death rates, disease incidence in specific racial and ethnic populations as well as in adolescents and young adults, and associations between melanoma incidence and solar ultraviolet exposure and socioeconomic indicators. Also included are data on melanoma mortality and survival, sun-related behaviors such as tanning and sunscreen use, and rates of reporting.

The authors mentioned above declared no relevant conflicts of interest; the supplement was supported by the CDC.

Melanoma was diagnosed in more than 45,000 people annually in the United States during 2004-2006, with a rate of 19 per 100,000 people.

That statistic, from two population-based cancer registries covering 78% of the U.S. population for those years, was among the melanoma data published in a series of articles in a special supplement to the November issue of the Journal of the American Academy of Dermatology (2011;65:S1-S156).

Among other significant findings were the following:

• Melanoma mortality accounted for $3.5 billion in lost productivity each year, with approximately $2.4 billion for men (average, $441,903 per man) and $1.2 billion for women (average, $401,046 per woman). Those who died from melanoma did so 20 years prematurely, compared with 17 years from other cancers, reported Donatus Ekwueme, Ph.D., of the Centers for Disease Control and Prevention.

• Melanoma rates were higher among white women aged 50 years and younger, Hispanic women aged 50 and younger, and Asian Pacific Islander women aged 40 and younger, compared with their male counterparts. Hispanics, American Indians/Alaska Natives, and Asians were diagnosed with melanoma at younger ages than were whites and blacks, according to analysis from Dr. Xiao-Cheng Wu of the school of public health at Louisiana State University in New Orleans.

• In 2005, 34% of adults reported having been sunburned in the past year, compared with 69% of adolescents, David Buller, Ph.D., of Klein Buendel Inc., a research firm, said in a report that also addressed the prevalence of sunburn, sun protection, and indoor-tanning behaviors.

• Fully 50% of dermatologists were unaware that they are required by state law to report their diagnosed cases of melanoma to their state central cancer registry, based on a survey of more than 400 dermatologists at a medical meeting. A slightly higher percentage (56%) do not actively report their melanoma diagnoses to a registry, according to the findings of the survey conducted by Dr. Todd Cartee of Emory University, Atlanta.

Other topics addressed include recent cutaneous melanoma trends and death rates, disease incidence in specific racial and ethnic populations as well as in adolescents and young adults, and associations between melanoma incidence and solar ultraviolet exposure and socioeconomic indicators. Also included are data on melanoma mortality and survival, sun-related behaviors such as tanning and sunscreen use, and rates of reporting.

The authors mentioned above declared no relevant conflicts of interest; the supplement was supported by the CDC.

The cost of treating diabetes patients in an adult practice exceeds reimbursement by more than $750,000 per year, and in a pediatric practice by more than $471,000 per year, according to the results of a study commissioned by several major diabetes and endocrinology organizations.

The economic data were part of a larger program that included a provider survey aimed at identifying barriers to providing optimal care for patients with diabetes and a set of recommendations that will be released in a white paper in December. The study was conducted by Avalere Health LLC on behalf of a working group comprising members of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Juvenile Diabetes and Research Foundation, the Pediatric Endocrine Society and the Endocrine Society. Also participating were representatives from the consulting company Close Concerns, the American Academy of Pediatrics, and three prominent individual endocrinologists (Dr. Bruce Bode, Dr. Irl Hirsch, and Dr. William Tamborlane).

The working group defined "optimal diabetes management" as "a patient-centered, multidisciplinary team approach to achieve evidence-based clinical outcomes [from major trials] shown to improve the long-term health of patients with diabetes," Avalere vice-president Jenifer Levinson said.

The survey, fielded to 1,422 unique members of the participating organizations, was completed by 1,056 respondents who provide care to diabetes patients. "Patient compliance" was the most frequently identified barrier to meeting established ADA and/or AACE diabetes standards of care, listed by 64% of the survey respondents. "Time with patients" was next, endorsed by 38%, followed by "compensation," 26%, and "team coordination," 26%. (Respondents could list more than one barrier.)

The economic analysis was carried out for six different patient vignettes, including those of three type 2 diabetes patients of different ages (40, 50, and 67 years) and three type 1 patients, aged 10, 16, and 67 years. Total reimbursement was calculated using the 2011 Medicare National Average Allowable nonfacility reimbursement rates, which include the 20% patient coinsurance. For non-Medicare vignettes, a standard multiplier was used to estimate private insurer and Medicaid payment rates.

The baseline model showed a gap between provider costs and reimbursement of $121-$829/patient per year, depending on patient characteristics. Reimbursement exceeded provider costs only for the best-case provider time estimates, in five of the six patient scenarios, by $28-$243/patient per year. However, in "real-world" estimates, the costs of treating adult diabetes patients exceeded reimbursement by $754,623/practice, and for treating pediatric patients by $471,098. These gaps are increased for patients using time-intensive management technologies such as insulin pumps and continuous glucose monitors.

Ms. Levinson commented that diabetes providers offset these losses in a variety of ways, including seeing other types of patients, conducting clinical research, and, commonly, seeing as many patients as possible in a day’s time. "When you look at just diabetes patients for an average practice, the losses on an annual basis are fairly significant and probably start to help explain some of those barriers, like the ability to spend time with patients. The less time you spend with patients, the more patients you can see and that may help prevent losses. But it also explains why it’s hard to provide optimal evidence-based care. If you’re going to lose that much money providing optimal care, it’s going to be very challenging to do and certainly a significant barrier."

The model used in the study is highly sensitive to assumptions about coverage and reimbursement for diabetes-related services, particularly for physician office visits, and the figures are likely to be underestimates because of the conservative assumptions used in the model. For instance, the study assumed that an hour-long visit would be coded as such. However, in reality providers often "down-code" to a visit of lower duration or complexity because it is less likely to be denied by payers than are longer/more complex office visits, Ms. Levinson said.

"So, we were conservative in that respect. If you assume that providers get paid only for lower-level visit, losses were much higher," she said, adding that this was true for diabetes educators as well as physicians, since payers often limit the time that educators or nutritionists can spend with patients.

To address the three key provider barriers addressed in the survey – time with patients, inadequate reimbursement, and patient compliance – the working group provided three sets of recommendations.

For care management, the group recommended the following:

• Increase use of shared decision-making opportunities with patients in the office setting to maximize patient engagement in self-management of diabetes.

• Leverage existing health information technology tools fully to assist patients in diabetes self-management and track performance.

• Create strong provider teams and share roles and expectations with patients.

For payment reform, they recommended:

• Reimburse providers appropriately for meeting standards of care in treating their patients by paying adequately for all services delivered.

• Test and implement payment models that reward providers for supplying optimal care to patients with diabetes.

And to address workforce supply:

• Work to make diabetes care an attractive choice for new medical professionals through educational loan forgiveness.

• Promote the importance of providing optimal diabetes care as an essential aspect of the health care system.

• Expand access to diabetes modules to educate primary care providers on treatment of diabetes.

The study was funded by Medtronic, Abbott, Bayer, DexCom, Johnson & Johnson, Roche, and Sanofi-Aventis. However, the working group members were not individually compensated.

The cost of treating diabetes patients in an adult practice exceeds reimbursement by more than $750,000 per year, and in a pediatric practice by more than $471,000 per year, according to the results of a study commissioned by several major diabetes and endocrinology organizations.

The economic data were part of a larger program that included a provider survey aimed at identifying barriers to providing optimal care for patients with diabetes and a set of recommendations that will be released in a white paper in December. The study was conducted by Avalere Health LLC on behalf of a working group comprising members of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Juvenile Diabetes and Research Foundation, the Pediatric Endocrine Society and the Endocrine Society. Also participating were representatives from the consulting company Close Concerns, the American Academy of Pediatrics, and three prominent individual endocrinologists (Dr. Bruce Bode, Dr. Irl Hirsch, and Dr. William Tamborlane).

The working group defined "optimal diabetes management" as "a patient-centered, multidisciplinary team approach to achieve evidence-based clinical outcomes [from major trials] shown to improve the long-term health of patients with diabetes," Avalere vice-president Jenifer Levinson said.

The survey, fielded to 1,422 unique members of the participating organizations, was completed by 1,056 respondents who provide care to diabetes patients. "Patient compliance" was the most frequently identified barrier to meeting established ADA and/or AACE diabetes standards of care, listed by 64% of the survey respondents. "Time with patients" was next, endorsed by 38%, followed by "compensation," 26%, and "team coordination," 26%. (Respondents could list more than one barrier.)

The economic analysis was carried out for six different patient vignettes, including those of three type 2 diabetes patients of different ages (40, 50, and 67 years) and three type 1 patients, aged 10, 16, and 67 years. Total reimbursement was calculated using the 2011 Medicare National Average Allowable nonfacility reimbursement rates, which include the 20% patient coinsurance. For non-Medicare vignettes, a standard multiplier was used to estimate private insurer and Medicaid payment rates.

The baseline model showed a gap between provider costs and reimbursement of $121-$829/patient per year, depending on patient characteristics. Reimbursement exceeded provider costs only for the best-case provider time estimates, in five of the six patient scenarios, by $28-$243/patient per year. However, in "real-world" estimates, the costs of treating adult diabetes patients exceeded reimbursement by $754,623/practice, and for treating pediatric patients by $471,098. These gaps are increased for patients using time-intensive management technologies such as insulin pumps and continuous glucose monitors.

Ms. Levinson commented that diabetes providers offset these losses in a variety of ways, including seeing other types of patients, conducting clinical research, and, commonly, seeing as many patients as possible in a day’s time. "When you look at just diabetes patients for an average practice, the losses on an annual basis are fairly significant and probably start to help explain some of those barriers, like the ability to spend time with patients. The less time you spend with patients, the more patients you can see and that may help prevent losses. But it also explains why it’s hard to provide optimal evidence-based care. If you’re going to lose that much money providing optimal care, it’s going to be very challenging to do and certainly a significant barrier."

The model used in the study is highly sensitive to assumptions about coverage and reimbursement for diabetes-related services, particularly for physician office visits, and the figures are likely to be underestimates because of the conservative assumptions used in the model. For instance, the study assumed that an hour-long visit would be coded as such. However, in reality providers often "down-code" to a visit of lower duration or complexity because it is less likely to be denied by payers than are longer/more complex office visits, Ms. Levinson said.

"So, we were conservative in that respect. If you assume that providers get paid only for lower-level visit, losses were much higher," she said, adding that this was true for diabetes educators as well as physicians, since payers often limit the time that educators or nutritionists can spend with patients.

To address the three key provider barriers addressed in the survey – time with patients, inadequate reimbursement, and patient compliance – the working group provided three sets of recommendations.

For care management, the group recommended the following:

• Increase use of shared decision-making opportunities with patients in the office setting to maximize patient engagement in self-management of diabetes.

• Leverage existing health information technology tools fully to assist patients in diabetes self-management and track performance.

• Create strong provider teams and share roles and expectations with patients.

For payment reform, they recommended:

• Reimburse providers appropriately for meeting standards of care in treating their patients by paying adequately for all services delivered.

• Test and implement payment models that reward providers for supplying optimal care to patients with diabetes.

And to address workforce supply:

• Work to make diabetes care an attractive choice for new medical professionals through educational loan forgiveness.

• Promote the importance of providing optimal diabetes care as an essential aspect of the health care system.

• Expand access to diabetes modules to educate primary care providers on treatment of diabetes.

The study was funded by Medtronic, Abbott, Bayer, DexCom, Johnson & Johnson, Roche, and Sanofi-Aventis. However, the working group members were not individually compensated.

The cost of treating diabetes patients in an adult practice exceeds reimbursement by more than $750,000 per year, and in a pediatric practice by more than $471,000 per year, according to the results of a study commissioned by several major diabetes and endocrinology organizations.

The economic data were part of a larger program that included a provider survey aimed at identifying barriers to providing optimal care for patients with diabetes and a set of recommendations that will be released in a white paper in December. The study was conducted by Avalere Health LLC on behalf of a working group comprising members of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Juvenile Diabetes and Research Foundation, the Pediatric Endocrine Society and the Endocrine Society. Also participating were representatives from the consulting company Close Concerns, the American Academy of Pediatrics, and three prominent individual endocrinologists (Dr. Bruce Bode, Dr. Irl Hirsch, and Dr. William Tamborlane).

The working group defined "optimal diabetes management" as "a patient-centered, multidisciplinary team approach to achieve evidence-based clinical outcomes [from major trials] shown to improve the long-term health of patients with diabetes," Avalere vice-president Jenifer Levinson said.

The survey, fielded to 1,422 unique members of the participating organizations, was completed by 1,056 respondents who provide care to diabetes patients. "Patient compliance" was the most frequently identified barrier to meeting established ADA and/or AACE diabetes standards of care, listed by 64% of the survey respondents. "Time with patients" was next, endorsed by 38%, followed by "compensation," 26%, and "team coordination," 26%. (Respondents could list more than one barrier.)

The economic analysis was carried out for six different patient vignettes, including those of three type 2 diabetes patients of different ages (40, 50, and 67 years) and three type 1 patients, aged 10, 16, and 67 years. Total reimbursement was calculated using the 2011 Medicare National Average Allowable nonfacility reimbursement rates, which include the 20% patient coinsurance. For non-Medicare vignettes, a standard multiplier was used to estimate private insurer and Medicaid payment rates.

The baseline model showed a gap between provider costs and reimbursement of $121-$829/patient per year, depending on patient characteristics. Reimbursement exceeded provider costs only for the best-case provider time estimates, in five of the six patient scenarios, by $28-$243/patient per year. However, in "real-world" estimates, the costs of treating adult diabetes patients exceeded reimbursement by $754,623/practice, and for treating pediatric patients by $471,098. These gaps are increased for patients using time-intensive management technologies such as insulin pumps and continuous glucose monitors.

Ms. Levinson commented that diabetes providers offset these losses in a variety of ways, including seeing other types of patients, conducting clinical research, and, commonly, seeing as many patients as possible in a day’s time. "When you look at just diabetes patients for an average practice, the losses on an annual basis are fairly significant and probably start to help explain some of those barriers, like the ability to spend time with patients. The less time you spend with patients, the more patients you can see and that may help prevent losses. But it also explains why it’s hard to provide optimal evidence-based care. If you’re going to lose that much money providing optimal care, it’s going to be very challenging to do and certainly a significant barrier."

The model used in the study is highly sensitive to assumptions about coverage and reimbursement for diabetes-related services, particularly for physician office visits, and the figures are likely to be underestimates because of the conservative assumptions used in the model. For instance, the study assumed that an hour-long visit would be coded as such. However, in reality providers often "down-code" to a visit of lower duration or complexity because it is less likely to be denied by payers than are longer/more complex office visits, Ms. Levinson said.

"So, we were conservative in that respect. If you assume that providers get paid only for lower-level visit, losses were much higher," she said, adding that this was true for diabetes educators as well as physicians, since payers often limit the time that educators or nutritionists can spend with patients.

To address the three key provider barriers addressed in the survey – time with patients, inadequate reimbursement, and patient compliance – the working group provided three sets of recommendations.

For care management, the group recommended the following:

• Increase use of shared decision-making opportunities with patients in the office setting to maximize patient engagement in self-management of diabetes.

• Leverage existing health information technology tools fully to assist patients in diabetes self-management and track performance.

• Create strong provider teams and share roles and expectations with patients.

For payment reform, they recommended:

• Reimburse providers appropriately for meeting standards of care in treating their patients by paying adequately for all services delivered.

• Test and implement payment models that reward providers for supplying optimal care to patients with diabetes.

And to address workforce supply:

• Work to make diabetes care an attractive choice for new medical professionals through educational loan forgiveness.

• Promote the importance of providing optimal diabetes care as an essential aspect of the health care system.

• Expand access to diabetes modules to educate primary care providers on treatment of diabetes.

The study was funded by Medtronic, Abbott, Bayer, DexCom, Johnson & Johnson, Roche, and Sanofi-Aventis. However, the working group members were not individually compensated.

LISBON – A novel investigational chemokine receptor antagonist produced a statistically significant decrease in hemoglobin A_1c and a higher percentage of HbA_1c responders, compared with placebo after 4 weeks of treatment in a phase II multinational study of 159 patients with type 2 diabetes who were already taking metformin.

The compound, ChemoCentryx’s CCX140-B, works by blocking the infiltration and activation of certain monocytes/macrophages and other cells bearing chemokine receptor 2 that occur during inflammation and are implicated in the development of insulin resistance in type 2 diabetes. The agent is designed to provide selective treatment without compromising other immune functions, said Dr. Markolf Hanefeld, director of the Centre for Clinical Studies, Technical University Dresden (Germany).

The subjects had been on stable metformin treatment for at least 8 weeks before study entry. They had a mean age of 59 years, were 64% male, had a mean body mass index of 32 kg/m², median diabetes duration of 5.8 years. At baseline, they had a mean hemoglobin A_1c value of 7.5% and mean fasting plasma glucose of 170 mg/dL. They were randomized to receive 5 mg/day CCX140-B, 10 mg/day CCX140-B, placebo, or open-label 30 mg/day pioglitazone as an active comparator.

Reductions in HbA_1c from baseline at week 4 were 0.09 percentage points with both placebo and the 5 mg CCX140-B group, 0.23 for the 10 mg CCX140-B group, and 0.13 with pioglitazone. The difference, compared with placebo, was significant for 10 mg CCX140-B (P = .045) but not for pioglitazone. The percentage of patients who had a decrease in HbA_1c from baseline to week 4 was 58% for placebo, 51% for 5mg CCX140-B, 82% for 10 mg CCX140-B, and 77% for pioglitazone. Again, the difference from placebo was significant for 10 mg CCX140-B (P = 0.45) but not for 5 mg CCX140-B or pioglitazone, Dr. Hanefeld reported.

Treatment with CCX140-B also showed a dose-dependent decrease in fasting glucose through week 4, he noted.

There were no safety concerns regarding laboratory hematology, chemistry, or urinalysis. In contrast to what has been seen with other CCR2 agonists in animal studies, there were no significant changes in plasma MCP-1 or blood monocyte count with CCX140-B. There were also no significant changes in body weight or any evidence of hemodilution or peripheral edema, and there was no effect on HDL cholesterol or LDL cholesterol. There was a slight decrease in triglycerides with pioglitazone but not with CCX140-B, he said.

In a separate rodent study presented at EASD, CCX140-B significantly improved metabolic/renal parameters including hyperglycemia, insulin sensitivity, serum adiponectin, glucosuria, albuminuria, and serum markers (creatine and BUN) of renal function. The metabolic improvements correlated with a significant reduction in adipose tissue macrophage numbers. ChemoCentryx will soon be initiating phase II clinical studies of CCX140-B for the treatment of diabetic nephropathy, according to a company statement.

Dr. Hanefeld has received lecture honoraria from Bayer AG, Takeda Pharmaceutical, GlaxoSmithKline, Sanofi-Aventis, and Boehringer-Ingelheim. He is also a consultant for Sanofi-Aventis and Eli Lilly.

LISBON – A novel investigational chemokine receptor antagonist produced a statistically significant decrease in hemoglobin A_1c and a higher percentage of HbA_1c responders, compared with placebo after 4 weeks of treatment in a phase II multinational study of 159 patients with type 2 diabetes who were already taking metformin.

The compound, ChemoCentryx’s CCX140-B, works by blocking the infiltration and activation of certain monocytes/macrophages and other cells bearing chemokine receptor 2 that occur during inflammation and are implicated in the development of insulin resistance in type 2 diabetes. The agent is designed to provide selective treatment without compromising other immune functions, said Dr. Markolf Hanefeld, director of the Centre for Clinical Studies, Technical University Dresden (Germany).

The subjects had been on stable metformin treatment for at least 8 weeks before study entry. They had a mean age of 59 years, were 64% male, had a mean body mass index of 32 kg/m², median diabetes duration of 5.8 years. At baseline, they had a mean hemoglobin A_1c value of 7.5% and mean fasting plasma glucose of 170 mg/dL. They were randomized to receive 5 mg/day CCX140-B, 10 mg/day CCX140-B, placebo, or open-label 30 mg/day pioglitazone as an active comparator.

Reductions in HbA_1c from baseline at week 4 were 0.09 percentage points with both placebo and the 5 mg CCX140-B group, 0.23 for the 10 mg CCX140-B group, and 0.13 with pioglitazone. The difference, compared with placebo, was significant for 10 mg CCX140-B (P = .045) but not for pioglitazone. The percentage of patients who had a decrease in HbA_1c from baseline to week 4 was 58% for placebo, 51% for 5mg CCX140-B, 82% for 10 mg CCX140-B, and 77% for pioglitazone. Again, the difference from placebo was significant for 10 mg CCX140-B (P = 0.45) but not for 5 mg CCX140-B or pioglitazone, Dr. Hanefeld reported.

Treatment with CCX140-B also showed a dose-dependent decrease in fasting glucose through week 4, he noted.

There were no safety concerns regarding laboratory hematology, chemistry, or urinalysis. In contrast to what has been seen with other CCR2 agonists in animal studies, there were no significant changes in plasma MCP-1 or blood monocyte count with CCX140-B. There were also no significant changes in body weight or any evidence of hemodilution or peripheral edema, and there was no effect on HDL cholesterol or LDL cholesterol. There was a slight decrease in triglycerides with pioglitazone but not with CCX140-B, he said.

In a separate rodent study presented at EASD, CCX140-B significantly improved metabolic/renal parameters including hyperglycemia, insulin sensitivity, serum adiponectin, glucosuria, albuminuria, and serum markers (creatine and BUN) of renal function. The metabolic improvements correlated with a significant reduction in adipose tissue macrophage numbers. ChemoCentryx will soon be initiating phase II clinical studies of CCX140-B for the treatment of diabetic nephropathy, according to a company statement.

Dr. Hanefeld has received lecture honoraria from Bayer AG, Takeda Pharmaceutical, GlaxoSmithKline, Sanofi-Aventis, and Boehringer-Ingelheim. He is also a consultant for Sanofi-Aventis and Eli Lilly.

LISBON – A novel investigational chemokine receptor antagonist produced a statistically significant decrease in hemoglobin A_1c and a higher percentage of HbA_1c responders, compared with placebo after 4 weeks of treatment in a phase II multinational study of 159 patients with type 2 diabetes who were already taking metformin.

The compound, ChemoCentryx’s CCX140-B, works by blocking the infiltration and activation of certain monocytes/macrophages and other cells bearing chemokine receptor 2 that occur during inflammation and are implicated in the development of insulin resistance in type 2 diabetes. The agent is designed to provide selective treatment without compromising other immune functions, said Dr. Markolf Hanefeld, director of the Centre for Clinical Studies, Technical University Dresden (Germany).

The subjects had been on stable metformin treatment for at least 8 weeks before study entry. They had a mean age of 59 years, were 64% male, had a mean body mass index of 32 kg/m², median diabetes duration of 5.8 years. At baseline, they had a mean hemoglobin A_1c value of 7.5% and mean fasting plasma glucose of 170 mg/dL. They were randomized to receive 5 mg/day CCX140-B, 10 mg/day CCX140-B, placebo, or open-label 30 mg/day pioglitazone as an active comparator.

Reductions in HbA_1c from baseline at week 4 were 0.09 percentage points with both placebo and the 5 mg CCX140-B group, 0.23 for the 10 mg CCX140-B group, and 0.13 with pioglitazone. The difference, compared with placebo, was significant for 10 mg CCX140-B (P = .045) but not for pioglitazone. The percentage of patients who had a decrease in HbA_1c from baseline to week 4 was 58% for placebo, 51% for 5mg CCX140-B, 82% for 10 mg CCX140-B, and 77% for pioglitazone. Again, the difference from placebo was significant for 10 mg CCX140-B (P = 0.45) but not for 5 mg CCX140-B or pioglitazone, Dr. Hanefeld reported.

Treatment with CCX140-B also showed a dose-dependent decrease in fasting glucose through week 4, he noted.

There were no safety concerns regarding laboratory hematology, chemistry, or urinalysis. In contrast to what has been seen with other CCR2 agonists in animal studies, there were no significant changes in plasma MCP-1 or blood monocyte count with CCX140-B. There were also no significant changes in body weight or any evidence of hemodilution or peripheral edema, and there was no effect on HDL cholesterol or LDL cholesterol. There was a slight decrease in triglycerides with pioglitazone but not with CCX140-B, he said.

In a separate rodent study presented at EASD, CCX140-B significantly improved metabolic/renal parameters including hyperglycemia, insulin sensitivity, serum adiponectin, glucosuria, albuminuria, and serum markers (creatine and BUN) of renal function. The metabolic improvements correlated with a significant reduction in adipose tissue macrophage numbers. ChemoCentryx will soon be initiating phase II clinical studies of CCX140-B for the treatment of diabetic nephropathy, according to a company statement.

Dr. Hanefeld has received lecture honoraria from Bayer AG, Takeda Pharmaceutical, GlaxoSmithKline, Sanofi-Aventis, and Boehringer-Ingelheim. He is also a consultant for Sanofi-Aventis and Eli Lilly.

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization’s criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered," said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:(Suppl. 2):S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks’ gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would "substantially increase the frequency of hyperglycemic disorders in pregnancy," compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered."

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m²), whereas the Middle Eastern women had a higher average BMI (25.9). Both ethnic minority groups were more likely than Scandinavian women to have a first-degree relative with diabetes (47% of South Asian women and 39% of Middle Eastern, vs. 13% of Scandinavian). Both minority groups were also shorter on average, and had more previous pregnancies and lower educational levels, she reported.

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a "two-step" method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour "loading" test at 24-28 weeks’ gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

"There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes, and it would lead to a significant increase in health care costs," the ACOG authors noted, adding that "significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes."

ACOG and other organizations are looking ahead to the National Institutes of Health’s Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus, scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. "Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM," the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Neither Dr. Morkrid nor Dr. Diamant had any financial disclosures.

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization’s criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered," said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:(Suppl. 2):S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks’ gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would "substantially increase the frequency of hyperglycemic disorders in pregnancy," compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered."

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m²), whereas the Middle Eastern women had a higher average BMI (25.9). Both ethnic minority groups were more likely than Scandinavian women to have a first-degree relative with diabetes (47% of South Asian women and 39% of Middle Eastern, vs. 13% of Scandinavian). Both minority groups were also shorter on average, and had more previous pregnancies and lower educational levels, she reported.

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a "two-step" method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour "loading" test at 24-28 weeks’ gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

"There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes, and it would lead to a significant increase in health care costs," the ACOG authors noted, adding that "significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes."

ACOG and other organizations are looking ahead to the National Institutes of Health’s Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus, scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. "Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM," the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Neither Dr. Morkrid nor Dr. Diamant had any financial disclosures.

LISBON – Use of the recently proposed International Association of Diabetes and Pregnancy Study Group criteria for identifying women with gestational diabetes would increase the diagnosis by 240%, compared with the World Health Organization’s criteria, according to the findings of a population-based multiethnic cohort study of 823 healthy pregnant women in Norway.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered," said Dr. Kjersti Morkrid of the department of endocrinology at Oslo University Hospital and the Institute of Clinical Medicine at the University of Oslo.

The IADPSG criteria were derived from an international workshop held in Pasadena, Calif., in which 225 conferees from 40 countries reviewed the results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study and other data suggesting that there is a risk for adverse fetal outcomes below current gestational diabetes mellitus (GDM) diagnostic thresholds. Indeed, currently used criteria were either chosen to identify women at risk for the later development of diabetes (Diabetes Care 2007;30:(Suppl. 2):S251-60), or were derived from nonpregnant individuals (World Health Org. Tech. Rep. Ser. 1980;646:1-80) and were not primarily aimed at identifying pregnancies with increased risk for adverse perinatal outcome, the IADPSG authors noted (Diabetes Care 2010;33:676-91).

The newly proposed criteria, which have been endorsed by the American Diabetes Association but not the American College of Obstetricians and Gynecologists (ACOG), were aimed at identifying women who have a 75% increased risk for adverse fetal outcomes, including birth weight greater than the 90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord C-peptide above the 90th percentile (the primary HAPO outcomes).

The IADPSG criteria call for an initial measurement of fasting plasma glucose (FPG), random glucose, or hemoglobin A_1c level in all or just high-risk women at the first prenatal visit. If the results do not detect overt diabetes but the FPG is 92-126 mg/dL, then GDM is diagnosed. If the FPG is less than 92 mg/dL, then a single 75-g, 2-hour oral glucose tolerance test (OGTT) is performed at 24-28 weeks’ gestation. The OGTT should be performed after an overnight fast, with overt diabetes diagnosed if the fasting plasma glucose level is at least 126 mg/dL. GDM is diagnosed if the FPG is greater than 92 mg/dL, if the 1-hour value exceeds 180 mg/dL, or if the 2-hour value exceeds 153 mg/dL.

The IADPSG authors acknowledged that the criteria would "substantially increase the frequency of hyperglycemic disorders in pregnancy," compared with other criteria such as those of the World Health Organization, which diagnose GDM at 24-28 weeks by either an FPG of at least 126 mg/dL or a 2-hour value of at least 140 mg/dL or higher following a 75-g glucose load.

The Norwegian Stork Groruddalen Research Program quantified that increase in a multiethnic population, including 41% of the 823 from Scandinavia, 24% from South Asia (primarily Pakistan and Sri Lanka), and 15% from the Middle East (mainly from Iraq, Morocco, and Turkey), as well as others from Eastern Europe, East Asia, Somalia, sub-Saharan Africa, and South America.

"Before endorsing the IADPSG criteria, the impact of diagnosing nearly one-third of all pregnant women should be considered."

Compared with women from Scandinavia, those of South Asian and Middle Eastern origin were significantly younger on average (aged 28 and 29 years, respectively, vs. 30 years for Scandinavian women). South Asian women had lower prepregnancy body mass indexes compared with Scandinavian women (23.7 vs. 24.6 kg/m²), whereas the Middle Eastern women had a higher average BMI (25.9). Both ethnic minority groups were more likely than Scandinavian women to have a first-degree relative with diabetes (47% of South Asian women and 39% of Middle Eastern, vs. 13% of Scandinavian). Both minority groups were also shorter on average, and had more previous pregnancies and lower educational levels, she reported.

Of the 759 women who completed the OGTT at visit 2, GDM prevalence rates were 32% by the IADPSG criteria, compared with just 13% by the WHO criteria. The overall increase in GDM diagnosis was by a factor of 2.4, ranging from 2.2 for Scandinavian and Middle Eastern women to a 2.8-fold increase among Southeast Asian women.

There was poor overlap between the two criteria, with just 9% identified by both, 4% by only the WHO criteria, and 22% by only the IADPSG criteria. More than two-thirds who were identified by the IADPSG were not identified by WHO criteria, Dr. Morkrid pointed out.

After adjustment for ethnicity, age, BMI, body height, parity, education level, and first-degree relatives with diabetes, factors significantly associated with GDM by the WHO criteria were body height per cm (odds ratio, 0.92), low education level (OR, 1.83), and having a first degree relative with diabetes (OR, 2.28). With the IADPSG criteria, prepregnancy BMI (OR, 1.09) and South Asian origin (OR, 2.48) were the most significant factors.

In response to a question from the audience about fetal outcome, Dr. Morkrid responded that those data are available but have not yet been analyzed.

The IADPSG criteria have been adopted by some countries, including Japan and Germany, but not widely in the United States. In September 2010, the ACOG Committee on Obstetric Practice issued a committee opinion restating its recommendation for a "two-step" method that differs from both the IADPSG and WHO criteria, utilizing a 50-g, 1-hour "loading" test at 24-28 weeks’ gestation, followed by a confirmatory 100-g, 3-hour OGTT.

In addition to concerns regarding the dramatic increase in the number of women diagnosed with GDM that would occur with adoption of the IADPSG criteria – ACOG estimates the proportion would be 18% of all pregnant women – the ACOG committee opinion also cited the lack of evidence regarding impact on outcomes.

"There is no evidence that the identification and treatment of women based on the new [IADPSG] recommendations will lead to clinically significant improvements in maternal and neonatal outcomes, and it would lead to a significant increase in health care costs," the ACOG authors noted, adding that "significant questions remain regarding the implications on health care costs, the effect of GDM diagnosis on the pregnant woman and her family, the effect of diagnosis on obstetric interventions in pregnancy, and whether the identification and treatment of GDM will improve meaningful perinatal, neonatal, and maternal outcomes."

ACOG and other organizations are looking ahead to the National Institutes of Health’s Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus, scheduled for October 29-31, 2012, to develop a uniform diagnostic standard. "Consensus regarding optimal diagnostic criteria among the many groups and professional organizations will further much needed research regarding the benefits and harms of screening and diagnosis of GDM," the ACOG opinion statement said.

The Norwegian study was funded by the Research Council of Norway, the South-Eastern Norway Regional Health Authority, and the Norwegian Directorate of Health. Neither Dr. Morkrid nor Dr. Diamant had any financial disclosures.

Reoperation for failed antireflux surgery can be performed safely in experienced centers, but outcomes are not as good as with primary operations, according to the results of two new analyses.

Dr. Nicholas R.A. Symons of Imperial College, London, and his associates performed a systematic literature review of 20 studies comprising 930 operations in 922 patients. "We can conclude that laparoscopic revision antireflux surgery, when performed in units with an interest in this type of surgery, is feasible and safe but subject to somewhat greater risk of conversion, higher morbidity, longer hospital stay, and poorer outcomes than primary laparoscopic fundoplication," the researchers wrote in the American Journal of Surgery (2011;202:336-43).

Similarly, based on their retrospective study of 275 patients, Dr. Omar Awais of the University of Pittsburgh and his associates said, "Redo antireflux surgery can be performed safely in experienced centers, and as expected, the outcomes after redo antireflux surgery are not as good as [those of] first-time procedures. The operative approach depends on the underlying cause of failure" (Ann. Thorac. Surg. 2011;92:1083-90).

"Redo surgery after failed fundoplication is a complex operation."

Laparoscopic procedures are considered the gold standard treatment for severe gastroesophageal reflux because they appear to be more efficacious and less expensive than an open approach. Nonetheless, between 2.8% and 4.4% of patients who undergo laparoscopic fundoplication at a specialist center will require late reoperation for persistent or recurrent symptoms, and there may be an increased revision rate after primary laparoscopic antireflux surgery compared with an initial open approach. Revision of failed antireflux surgery increasingly is being performed laparoscopically, but data about this approach are limited, Dr. Symons and his associates noted.

Their analysis included 19 case-control series and one prospective case-control study. Patients ranged in age from 13 to 83 years, and 57% were female. Of the 8 articles in which the mean time between initial fundoplication and revision was given, the mean interval was 45.5 months (range 2-360 months). Of 12 studies noting the number of previous fundoplications the patients had undergone, 47 procedures (6.9%) were second reoperations and 9 (1.3%) were third reoperations.

Of the 18 studies documenting the type of initial surgery, 62% were laparoscopic, 35% were performed via laparotomy, 3% via thoracotomy, and 0.2% using video-assisted thoracoscopic surgery. Nissen fundoplication and Toupet partial fundoplication were the most common initial and revision procedures. Reflux/heartburn, experienced by 61% of patients, and dysphagia in 31% were the most common indications for laparoscopic reoperation, the investigators reported. Surgical duration, reported in 13 of the case series, ranged from 55 to 246 minutes, with an overall mean of 166 minutes for 721 patients. Previous studies have shown longer surgical times when the initial surgery was done laparoscopically compared with previous laparotomy, and also for revision surgery compared with primary surgery, Dr. Symons and his associates noted.

The overall rate of conversion from laparoscopic reoperation to open surgery – reported in all the studies – was 7.2%, while the rate for patients who had more than one previous fundoplication was 19%. The most common reason for conversion, reported in 16 studies, was adhesions from previous surgery. The overall 7.2% conversion rate is higher than that noted for primary surgery (3.7%), "but is not excessive given the increased complexity of revision surgery," they commented.

Postoperative complications, reported from 18 studies, occurred in 14%, ranging from 0% to 44%. There were two deaths, both occurring in the same study. Pneumothorax was the most common complication, in 2% (14/810). Mean length of stay, reported in 18 studies, ranged from 1.2 to 6 days.

Satisfactory to excellent results were reported for 84% of the operations, while 5% of patients had a further antireflux procedure. There was no significant correlation between the number of cases in a series and the mean surgical duration, conversion rate, postoperative complication rate, or reoperation rate.

While revision laparoscopic fundoplication does not confer excessive morbidity, evidence for the efficacy of this procedure "is far less convincing, mainly owing to the mixture of reporting time points, inconsistency of end point definitions, and methods of assessment between studies. There appears to be a larger proportion of patients undergoing a re-revision surgery than after primary fundoplication," Dr. Symons and his associates commented.

"This review is based on data from highly specialized units and, for these results to be reproduced, revision laparoscopic antireflux surgery should be performed by surgeons with experience and special interest in both laparoscopic and esophagogastric surgery," they concluded.

The single-center study included patients who underwent minimally invasive reoperative surgery after failed fundoplication at the University of Pittsburgh Medical Center from 1996 to 2008. The 275 patients had a median age of 52 years (range 17-88 years), and 11.3% had had more than one prior antireflux surgery. As with the systematic review, the most common presenting symptoms were heartburn (64%) and dysphagia (49.5%). The median time from the prior operation to the redo operation was 36 months.

"We can conclude that laparoscopic revision antireflux surgery ... is feasible and safe but subject to somewhat greater risk of conversion."

Transmediastinal migration of the wrap or a recurrent hiatal hernia (64%) were the most common causes of failure of the prior antireflux operation. Esophageal shortening was noted in 43% of patients, and a defect in the crural repair was identified in 4.4%. The most common procedure during reoperation was a Nissen fundoplication with or without a Collis gastroplasty. Nearly all of the redo procedures (93%) were done with a minimally invasive approach. There were eight conversions to open surgery due to extensive adhesions or a recognized intraoperative perforation, Dr. Awais and his associates reported.

Major complications included postoperative leaks in 3.3%; atrial fibrillation in 2%; and bleeding, pulmonary embolism, and Clostridium difficile colitis, each in less than 1%. Reexploration was required in 1.4%, for complications related to leak or bleeding. There was no perioperative mortality. Length of stay ranged from 1 to 75 days (median 3 days).

During follow-up of up to 14.5 years (median 3.3 years), 11.3% had a failure of the redo operation, requiring surgical intervention. An esophagectomy was required in 4 patients. The estimated probability of freedom from failure was 95% at 1 year, 93% at 2 years, and 84% at 5 years. Age and partial fundoplication were significantly associated with failure of the redo operation, and there was a trend for multiple redo operations to be associated with failure, Dr. Awais and his associates said.

Dysphagia decreased significantly after the redo procedure in 135 patients, with dysphagia scores declining from 2.7 to 1.4. Scores on the GERD-Health Related Quality of Life questionnaire, available in 186 patients, were excellent in 52% and satisfactory in 33%.

"Redo surgery after failed fundoplication is a complex operation, and a comprehensive evaluation should be completed prior to performing the procedure. ... Thoracic surgeons with significant laparoscopic and open esophageal surgical experience can perform minimally invasive complex redo esophageal antireflux procedures safely, with excellent to satisfactory results possible in more than 80% of patients using minimally invasive techniques at an experienced center," Dr. Awais and his associates concluded.

Both Dr. Symons and Dr. Awais stated that they had no disclosures.

Reoperation for failed antireflux surgery can be performed safely in experienced centers, but outcomes are not as good as with primary operations, according to the results of two new analyses.

Dr. Nicholas R.A. Symons of Imperial College, London, and his associates performed a systematic literature review of 20 studies comprising 930 operations in 922 patients. "We can conclude that laparoscopic revision antireflux surgery, when performed in units with an interest in this type of surgery, is feasible and safe but subject to somewhat greater risk of conversion, higher morbidity, longer hospital stay, and poorer outcomes than primary laparoscopic fundoplication," the researchers wrote in the American Journal of Surgery (2011;202:336-43).

Similarly, based on their retrospective study of 275 patients, Dr. Omar Awais of the University of Pittsburgh and his associates said, "Redo antireflux surgery can be performed safely in experienced centers, and as expected, the outcomes after redo antireflux surgery are not as good as [those of] first-time procedures. The operative approach depends on the underlying cause of failure" (Ann. Thorac. Surg. 2011;92:1083-90).

"Redo surgery after failed fundoplication is a complex operation."

Laparoscopic procedures are considered the gold standard treatment for severe gastroesophageal reflux because they appear to be more efficacious and less expensive than an open approach. Nonetheless, between 2.8% and 4.4% of patients who undergo laparoscopic fundoplication at a specialist center will require late reoperation for persistent or recurrent symptoms, and there may be an increased revision rate after primary laparoscopic antireflux surgery compared with an initial open approach. Revision of failed antireflux surgery increasingly is being performed laparoscopically, but data about this approach are limited, Dr. Symons and his associates noted.

Their analysis included 19 case-control series and one prospective case-control study. Patients ranged in age from 13 to 83 years, and 57% were female. Of the 8 articles in which the mean time between initial fundoplication and revision was given, the mean interval was 45.5 months (range 2-360 months). Of 12 studies noting the number of previous fundoplications the patients had undergone, 47 procedures (6.9%) were second reoperations and 9 (1.3%) were third reoperations.

Of the 18 studies documenting the type of initial surgery, 62% were laparoscopic, 35% were performed via laparotomy, 3% via thoracotomy, and 0.2% using video-assisted thoracoscopic surgery. Nissen fundoplication and Toupet partial fundoplication were the most common initial and revision procedures. Reflux/heartburn, experienced by 61% of patients, and dysphagia in 31% were the most common indications for laparoscopic reoperation, the investigators reported. Surgical duration, reported in 13 of the case series, ranged from 55 to 246 minutes, with an overall mean of 166 minutes for 721 patients. Previous studies have shown longer surgical times when the initial surgery was done laparoscopically compared with previous laparotomy, and also for revision surgery compared with primary surgery, Dr. Symons and his associates noted.

The overall rate of conversion from laparoscopic reoperation to open surgery – reported in all the studies – was 7.2%, while the rate for patients who had more than one previous fundoplication was 19%. The most common reason for conversion, reported in 16 studies, was adhesions from previous surgery. The overall 7.2% conversion rate is higher than that noted for primary surgery (3.7%), "but is not excessive given the increased complexity of revision surgery," they commented.

Postoperative complications, reported from 18 studies, occurred in 14%, ranging from 0% to 44%. There were two deaths, both occurring in the same study. Pneumothorax was the most common complication, in 2% (14/810). Mean length of stay, reported in 18 studies, ranged from 1.2 to 6 days.

Satisfactory to excellent results were reported for 84% of the operations, while 5% of patients had a further antireflux procedure. There was no significant correlation between the number of cases in a series and the mean surgical duration, conversion rate, postoperative complication rate, or reoperation rate.

While revision laparoscopic fundoplication does not confer excessive morbidity, evidence for the efficacy of this procedure "is far less convincing, mainly owing to the mixture of reporting time points, inconsistency of end point definitions, and methods of assessment between studies. There appears to be a larger proportion of patients undergoing a re-revision surgery than after primary fundoplication," Dr. Symons and his associates commented.

"This review is based on data from highly specialized units and, for these results to be reproduced, revision laparoscopic antireflux surgery should be performed by surgeons with experience and special interest in both laparoscopic and esophagogastric surgery," they concluded.

The single-center study included patients who underwent minimally invasive reoperative surgery after failed fundoplication at the University of Pittsburgh Medical Center from 1996 to 2008. The 275 patients had a median age of 52 years (range 17-88 years), and 11.3% had had more than one prior antireflux surgery. As with the systematic review, the most common presenting symptoms were heartburn (64%) and dysphagia (49.5%). The median time from the prior operation to the redo operation was 36 months.

"We can conclude that laparoscopic revision antireflux surgery ... is feasible and safe but subject to somewhat greater risk of conversion."

Transmediastinal migration of the wrap or a recurrent hiatal hernia (64%) were the most common causes of failure of the prior antireflux operation. Esophageal shortening was noted in 43% of patients, and a defect in the crural repair was identified in 4.4%. The most common procedure during reoperation was a Nissen fundoplication with or without a Collis gastroplasty. Nearly all of the redo procedures (93%) were done with a minimally invasive approach. There were eight conversions to open surgery due to extensive adhesions or a recognized intraoperative perforation, Dr. Awais and his associates reported.

Major complications included postoperative leaks in 3.3%; atrial fibrillation in 2%; and bleeding, pulmonary embolism, and Clostridium difficile colitis, each in less than 1%. Reexploration was required in 1.4%, for complications related to leak or bleeding. There was no perioperative mortality. Length of stay ranged from 1 to 75 days (median 3 days).

During follow-up of up to 14.5 years (median 3.3 years), 11.3% had a failure of the redo operation, requiring surgical intervention. An esophagectomy was required in 4 patients. The estimated probability of freedom from failure was 95% at 1 year, 93% at 2 years, and 84% at 5 years. Age and partial fundoplication were significantly associated with failure of the redo operation, and there was a trend for multiple redo operations to be associated with failure, Dr. Awais and his associates said.

Dysphagia decreased significantly after the redo procedure in 135 patients, with dysphagia scores declining from 2.7 to 1.4. Scores on the GERD-Health Related Quality of Life questionnaire, available in 186 patients, were excellent in 52% and satisfactory in 33%.

"Redo surgery after failed fundoplication is a complex operation, and a comprehensive evaluation should be completed prior to performing the procedure. ... Thoracic surgeons with significant laparoscopic and open esophageal surgical experience can perform minimally invasive complex redo esophageal antireflux procedures safely, with excellent to satisfactory results possible in more than 80% of patients using minimally invasive techniques at an experienced center," Dr. Awais and his associates concluded.

Both Dr. Symons and Dr. Awais stated that they had no disclosures.

Reoperation for failed antireflux surgery can be performed safely in experienced centers, but outcomes are not as good as with primary operations, according to the results of two new analyses.

Dr. Nicholas R.A. Symons of Imperial College, London, and his associates performed a systematic literature review of 20 studies comprising 930 operations in 922 patients. "We can conclude that laparoscopic revision antireflux surgery, when performed in units with an interest in this type of surgery, is feasible and safe but subject to somewhat greater risk of conversion, higher morbidity, longer hospital stay, and poorer outcomes than primary laparoscopic fundoplication," the researchers wrote in the American Journal of Surgery (2011;202:336-43).

Similarly, based on their retrospective study of 275 patients, Dr. Omar Awais of the University of Pittsburgh and his associates said, "Redo antireflux surgery can be performed safely in experienced centers, and as expected, the outcomes after redo antireflux surgery are not as good as [those of] first-time procedures. The operative approach depends on the underlying cause of failure" (Ann. Thorac. Surg. 2011;92:1083-90).

"Redo surgery after failed fundoplication is a complex operation."

Laparoscopic procedures are considered the gold standard treatment for severe gastroesophageal reflux because they appear to be more efficacious and less expensive than an open approach. Nonetheless, between 2.8% and 4.4% of patients who undergo laparoscopic fundoplication at a specialist center will require late reoperation for persistent or recurrent symptoms, and there may be an increased revision rate after primary laparoscopic antireflux surgery compared with an initial open approach. Revision of failed antireflux surgery increasingly is being performed laparoscopically, but data about this approach are limited, Dr. Symons and his associates noted.

Their analysis included 19 case-control series and one prospective case-control study. Patients ranged in age from 13 to 83 years, and 57% were female. Of the 8 articles in which the mean time between initial fundoplication and revision was given, the mean interval was 45.5 months (range 2-360 months). Of 12 studies noting the number of previous fundoplications the patients had undergone, 47 procedures (6.9%) were second reoperations and 9 (1.3%) were third reoperations.

Of the 18 studies documenting the type of initial surgery, 62% were laparoscopic, 35% were performed via laparotomy, 3% via thoracotomy, and 0.2% using video-assisted thoracoscopic surgery. Nissen fundoplication and Toupet partial fundoplication were the most common initial and revision procedures. Reflux/heartburn, experienced by 61% of patients, and dysphagia in 31% were the most common indications for laparoscopic reoperation, the investigators reported. Surgical duration, reported in 13 of the case series, ranged from 55 to 246 minutes, with an overall mean of 166 minutes for 721 patients. Previous studies have shown longer surgical times when the initial surgery was done laparoscopically compared with previous laparotomy, and also for revision surgery compared with primary surgery, Dr. Symons and his associates noted.

The overall rate of conversion from laparoscopic reoperation to open surgery – reported in all the studies – was 7.2%, while the rate for patients who had more than one previous fundoplication was 19%. The most common reason for conversion, reported in 16 studies, was adhesions from previous surgery. The overall 7.2% conversion rate is higher than that noted for primary surgery (3.7%), "but is not excessive given the increased complexity of revision surgery," they commented.

Postoperative complications, reported from 18 studies, occurred in 14%, ranging from 0% to 44%. There were two deaths, both occurring in the same study. Pneumothorax was the most common complication, in 2% (14/810). Mean length of stay, reported in 18 studies, ranged from 1.2 to 6 days.

Satisfactory to excellent results were reported for 84% of the operations, while 5% of patients had a further antireflux procedure. There was no significant correlation between the number of cases in a series and the mean surgical duration, conversion rate, postoperative complication rate, or reoperation rate.

While revision laparoscopic fundoplication does not confer excessive morbidity, evidence for the efficacy of this procedure "is far less convincing, mainly owing to the mixture of reporting time points, inconsistency of end point definitions, and methods of assessment between studies. There appears to be a larger proportion of patients undergoing a re-revision surgery than after primary fundoplication," Dr. Symons and his associates commented.

"This review is based on data from highly specialized units and, for these results to be reproduced, revision laparoscopic antireflux surgery should be performed by surgeons with experience and special interest in both laparoscopic and esophagogastric surgery," they concluded.

The single-center study included patients who underwent minimally invasive reoperative surgery after failed fundoplication at the University of Pittsburgh Medical Center from 1996 to 2008. The 275 patients had a median age of 52 years (range 17-88 years), and 11.3% had had more than one prior antireflux surgery. As with the systematic review, the most common presenting symptoms were heartburn (64%) and dysphagia (49.5%). The median time from the prior operation to the redo operation was 36 months.

"We can conclude that laparoscopic revision antireflux surgery ... is feasible and safe but subject to somewhat greater risk of conversion."

Transmediastinal migration of the wrap or a recurrent hiatal hernia (64%) were the most common causes of failure of the prior antireflux operation. Esophageal shortening was noted in 43% of patients, and a defect in the crural repair was identified in 4.4%. The most common procedure during reoperation was a Nissen fundoplication with or without a Collis gastroplasty. Nearly all of the redo procedures (93%) were done with a minimally invasive approach. There were eight conversions to open surgery due to extensive adhesions or a recognized intraoperative perforation, Dr. Awais and his associates reported.

Major complications included postoperative leaks in 3.3%; atrial fibrillation in 2%; and bleeding, pulmonary embolism, and Clostridium difficile colitis, each in less than 1%. Reexploration was required in 1.4%, for complications related to leak or bleeding. There was no perioperative mortality. Length of stay ranged from 1 to 75 days (median 3 days).

During follow-up of up to 14.5 years (median 3.3 years), 11.3% had a failure of the redo operation, requiring surgical intervention. An esophagectomy was required in 4 patients. The estimated probability of freedom from failure was 95% at 1 year, 93% at 2 years, and 84% at 5 years. Age and partial fundoplication were significantly associated with failure of the redo operation, and there was a trend for multiple redo operations to be associated with failure, Dr. Awais and his associates said.

Dysphagia decreased significantly after the redo procedure in 135 patients, with dysphagia scores declining from 2.7 to 1.4. Scores on the GERD-Health Related Quality of Life questionnaire, available in 186 patients, were excellent in 52% and satisfactory in 33%.

"Redo surgery after failed fundoplication is a complex operation, and a comprehensive evaluation should be completed prior to performing the procedure. ... Thoracic surgeons with significant laparoscopic and open esophageal surgical experience can perform minimally invasive complex redo esophageal antireflux procedures safely, with excellent to satisfactory results possible in more than 80% of patients using minimally invasive techniques at an experienced center," Dr. Awais and his associates concluded.

Both Dr. Symons and Dr. Awais stated that they had no disclosures.

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue (the first was a meeting in 2001 on HIV/AIDS), the UN issued a consensus document recognizing that “the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world.”

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-ensured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed efforts by the World Health Organization to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to “bring NCDs into our broader global health and development agenda.”

Nearly two-thirds (63%) of deaths worldwide result from noncommunicable diseases such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health.

Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are “the diseases that break the bank,” said Dr. Margaret Chan, WHO's director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

“Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day,” according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

“Groups from the food and drink industry…were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach,” the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013. This essentially enables a lack of accountability that the editorial authors deemed “a missed opportunity.”

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be “explicitly recognized and addressed. … Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO's ability to govern and advance public health, which will severely impair capacity to help member states address NCDs” (Lancet 2011 [doi:10.1016/S0140-6736 (11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, “the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed.”

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. “I think that industry has to be involved in the development of the options for policy, and in the implementation.

“The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the United Nations,” he said. “But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there.”

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability.

There is still a chance that the “25% by 2025” NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The NCD Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues.

“If the outcomes are strong, we will forgive governments for not agreeing to those at the summit,” Ms. Keeling concluded.

'If industry is not at the table, … the UN and the government will simply be lost' in terms of knowing the possibilities.

Source DR. YACH

In the UN declaration, member states agreed to reduce salt and sugars and eliminate trans fats in foods, and to increase access to health care systems.

Source Miriam E. Tucker/Elsevier Global Medical News

Focus on U.S. Agenda

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own countries' experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address.

“For the United States' part, under President Obama, the United States has made taking on chronic disease a major focus.”

Among the U.S. initiatives are the recently launched Million Hearts campaign (

http://millionhearts.hhs.gov

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue (the first was a meeting in 2001 on HIV/AIDS), the UN issued a consensus document recognizing that “the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world.”

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-ensured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed efforts by the World Health Organization to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to “bring NCDs into our broader global health and development agenda.”

Nearly two-thirds (63%) of deaths worldwide result from noncommunicable diseases such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health.

Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are “the diseases that break the bank,” said Dr. Margaret Chan, WHO's director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

“Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day,” according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

“Groups from the food and drink industry…were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach,” the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013. This essentially enables a lack of accountability that the editorial authors deemed “a missed opportunity.”

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be “explicitly recognized and addressed. … Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO's ability to govern and advance public health, which will severely impair capacity to help member states address NCDs” (Lancet 2011 [doi:10.1016/S0140-6736 (11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, “the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed.”

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. “I think that industry has to be involved in the development of the options for policy, and in the implementation.

“The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the United Nations,” he said. “But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there.”

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability.

There is still a chance that the “25% by 2025” NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The NCD Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues.

“If the outcomes are strong, we will forgive governments for not agreeing to those at the summit,” Ms. Keeling concluded.

'If industry is not at the table, … the UN and the government will simply be lost' in terms of knowing the possibilities.

Source DR. YACH

In the UN declaration, member states agreed to reduce salt and sugars and eliminate trans fats in foods, and to increase access to health care systems.

Source Miriam E. Tucker/Elsevier Global Medical News

Focus on U.S. Agenda

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own countries' experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address.

“For the United States' part, under President Obama, the United States has made taking on chronic disease a major focus.”

Among the U.S. initiatives are the recently launched Million Hearts campaign (

http://millionhearts.hhs.gov

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue (the first was a meeting in 2001 on HIV/AIDS), the UN issued a consensus document recognizing that “the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world.”

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-ensured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed efforts by the World Health Organization to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to “bring NCDs into our broader global health and development agenda.”

Nearly two-thirds (63%) of deaths worldwide result from noncommunicable diseases such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health.

Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are “the diseases that break the bank,” said Dr. Margaret Chan, WHO's director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

“Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day,” according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

“Groups from the food and drink industry…were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach,” the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013. This essentially enables a lack of accountability that the editorial authors deemed “a missed opportunity.”

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be “explicitly recognized and addressed. … Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO's ability to govern and advance public health, which will severely impair capacity to help member states address NCDs” (Lancet 2011 [doi:10.1016/S0140-6736 (11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, “the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed.”

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. “I think that industry has to be involved in the development of the options for policy, and in the implementation.

“The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the United Nations,” he said. “But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there.”

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability.

There is still a chance that the “25% by 2025” NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The NCD Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues.

“If the outcomes are strong, we will forgive governments for not agreeing to those at the summit,” Ms. Keeling concluded.

'If industry is not at the table, … the UN and the government will simply be lost' in terms of knowing the possibilities.

Source DR. YACH

In the UN declaration, member states agreed to reduce salt and sugars and eliminate trans fats in foods, and to increase access to health care systems.

Source Miriam E. Tucker/Elsevier Global Medical News

Focus on U.S. Agenda

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own countries' experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address.

“For the United States' part, under President Obama, the United States has made taking on chronic disease a major focus.”

Among the U.S. initiatives are the recently launched Million Hearts campaign (

http://millionhearts.hhs.gov

Major Finding: After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, risk for CVD events following pregnancy was elevated by an odds ratio of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking.

Data Source: Case-control study of 2,660 CVD event cases and 13,357 matched controls who had given birth to at least one child.

Disclosures: Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes in pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m

“Preventive strategies after pregnancy might need to be individualized depending on each woman's characteristics and risk profile,” said Dr. Erik Schwarcz of University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish quality registers from 1991 through 2008, were 4,590 women diagnosed with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19–61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls.

GDM history was present for 2.4% of cases and 1.2% of controls, a significant difference. Also significantly increased among cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. With a BMI of 20–25 as the referent, a BMI of 25–29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20–24) versus overweight (BMI 25 or greater), only overweight women had increased risk for CVD (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn't add any risk above and beyond that of smoking, Dr. Schwarcz explained.

'Preventive strategies after pregnancy might need to be individualized.'

Source DR. SCHWARCZ

Major Finding: After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, risk for CVD events following pregnancy was elevated by an odds ratio of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking.

Data Source: Case-control study of 2,660 CVD event cases and 13,357 matched controls who had given birth to at least one child.

Disclosures: Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes in pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m

“Preventive strategies after pregnancy might need to be individualized depending on each woman's characteristics and risk profile,” said Dr. Erik Schwarcz of University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish quality registers from 1991 through 2008, were 4,590 women diagnosed with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19–61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls.

GDM history was present for 2.4% of cases and 1.2% of controls, a significant difference. Also significantly increased among cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. With a BMI of 20–25 as the referent, a BMI of 25–29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20–24) versus overweight (BMI 25 or greater), only overweight women had increased risk for CVD (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn't add any risk above and beyond that of smoking, Dr. Schwarcz explained.

'Preventive strategies after pregnancy might need to be individualized.'

Source DR. SCHWARCZ

Major Finding: After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, risk for CVD events following pregnancy was elevated by an odds ratio of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking.

Data Source: Case-control study of 2,660 CVD event cases and 13,357 matched controls who had given birth to at least one child.

Disclosures: Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes in pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m

“Preventive strategies after pregnancy might need to be individualized depending on each woman's characteristics and risk profile,” said Dr. Erik Schwarcz of University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish quality registers from 1991 through 2008, were 4,590 women diagnosed with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19–61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls.

GDM history was present for 2.4% of cases and 1.2% of controls, a significant difference. Also significantly increased among cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. With a BMI of 20–25 as the referent, a BMI of 25–29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20–24) versus overweight (BMI 25 or greater), only overweight women had increased risk for CVD (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn't add any risk above and beyond that of smoking, Dr. Schwarcz explained.

'Preventive strategies after pregnancy might need to be individualized.'

Source DR. SCHWARCZ