Miriam E. Tucker

STOCKHOLM – Use of a "rule-in" hemoglobin A1c cut point of 6.8% and a "rule-out" value of 5.8%, with glucose testing for individuals who fall in the middle of the diagnostic cutoff, was more accurate in diagnosing type 2 diabetes than was a single cutoff value of 6.5%.

The finding from a multiethnic cohort study of 8,696 previously undiagnosed primary care patients addresses some of the concerns about false-positive and false-negative diagnoses associated with using a single measure of hemoglobin A1c. Multiple studies have shown that the 6.5% cutoff may be discordant with the results of an oral glucose tolerance test (OGTT), which is considered to be the standard diagnostic test for type 2 diabetes, said Dr. Samiul A. Mostafa, a clinical research fellow in the diabetes research unit of the University of Leicester (England).

In July 2009, an international expert committee recommended the use of hemoglobin A1c for diagnosing diabetes, with a diagnostic cutoff of 6.5% or above following a repeat confirmatory A1c test (Diabetes Care 2009;32:1327-34). In January 2010, the American Diabetes Association endorsed that recommendation (Diabetes Care 2010;33[suppl. 1]:S62-9). The European Association for the Study of Diabetes and the World Health Organization are expected to issue similar statements soon.

The study participants were identified from two systematic screening programs during 2002-2008. Three-quarters (75%) were white Europeans and 23% were South Asians from Pakistan, Bangladesh, and India. The mean A1c for the entire cohort was 5.7%. All underwent an OGTT and also had their HbA1c levels measured. Using the WHO criteria (a 2-hour plasma glucose level of 200 mg/dL or above, following a 75-g glucose load), the OGTT detected 291 individuals (3.3% of 8,696 study participants) with type 2 diabetes.

Among the white Europeans, use of the 6.5% A1c cutoff had a sensitivity of 62% and a positive predictive value of 45%. Based on an Australian study published earlier this year, the investigators chose to compare those values with a rule-out A1c cutoff of 5.5% and a rule-in cutoff of 7.0%, with a confirmatory OGTT used for those falling in between (Diabetes Care 2010;33:817-9).

That method gave an improved sensitivity of 98% and positive predictive value of 76% in the white European group. With either method, specificity and negative predictive values were close to 100%. For the South Asians, the 6.5% cutoff gave a sensitivity of 79% and positive predictive value of 36%, both of which improved to 99% and 68%, respectively, with the two–cut-point criteria. Again, specificity and negative predictive values were strong with either method, Dr. Mostafa reported.

"Impaired HbA1c," the term used for the values between the two cutoffs (5.6%-6.9%), was found in 59% of the total cohort, who thus required confirmatory tests. Noting that those in the impaired HbA1c group (55% of the total cohort) had A1c values between 5.6% and 6.4% (that is, lower than 6.5%), they tried various cut points and arrived at a rule-out value of 5.8% or below and a rule-in value of 6.8% or above. That left 28% of the total cohort in the "impaired HbA1c" category when defined as an A1c of 5.9%-6.7%.

"We believe [a rule-out value of 5.8% and a rule-in value of 6.8%] would be a more feasible strategy to implement in clinical practice," Dr. Mostafa said.

These cutoffs gave sensitivities of 92% for white Europeans and 98% for South Asians, and positive predictive values of 70% and 54%, respectively, while maintaining the nearly 100% specificity and negative predictive values for both ethnic groups. Despite the slight reductions in positive predictive values, "overall, we feel using the cut points of 5.8% and 6.8% is still diagnostically accurate, with the major advantage that only a quarter of the population would have to return for a subsequent test," he said.

In a final analysis, the investigators looked at mean HbA1c values in various undiagnosed populations. Compared with the U.K. cohort’s mean of 5.7%, the Australian cohort had a mean of 5.1%, which resulted in 24% falling into their 5.6%-6.9% "impaired HbA1c" category. That led to the hypothesis that broader cut points are acceptable when mean A1c is relatively low, but a tighter range is required when mean A1c is higher.

Studies conducted in Denmark and in India showed relatively high mean A1c values of 5.8% and 5.6%, respectively, similar to the U.K. group. Those populations would probably need to use narrower cut points to reduce the number of people who would require subsequent testing. In contrast, like the Australians, data from the U.S. National Health and Nutrition Examination Survey showed a 5.2% mean A1c, meaning that a broader cut point range might be feasible, Dr. Mostafa said.

Dr. Mostafa stated that he had no disclosures.

STOCKHOLM – Use of a "rule-in" hemoglobin A1c cut point of 6.8% and a "rule-out" value of 5.8%, with glucose testing for individuals who fall in the middle of the diagnostic cutoff, was more accurate in diagnosing type 2 diabetes than was a single cutoff value of 6.5%.

The finding from a multiethnic cohort study of 8,696 previously undiagnosed primary care patients addresses some of the concerns about false-positive and false-negative diagnoses associated with using a single measure of hemoglobin A1c. Multiple studies have shown that the 6.5% cutoff may be discordant with the results of an oral glucose tolerance test (OGTT), which is considered to be the standard diagnostic test for type 2 diabetes, said Dr. Samiul A. Mostafa, a clinical research fellow in the diabetes research unit of the University of Leicester (England).

In July 2009, an international expert committee recommended the use of hemoglobin A1c for diagnosing diabetes, with a diagnostic cutoff of 6.5% or above following a repeat confirmatory A1c test (Diabetes Care 2009;32:1327-34). In January 2010, the American Diabetes Association endorsed that recommendation (Diabetes Care 2010;33[suppl. 1]:S62-9). The European Association for the Study of Diabetes and the World Health Organization are expected to issue similar statements soon.

The study participants were identified from two systematic screening programs during 2002-2008. Three-quarters (75%) were white Europeans and 23% were South Asians from Pakistan, Bangladesh, and India. The mean A1c for the entire cohort was 5.7%. All underwent an OGTT and also had their HbA1c levels measured. Using the WHO criteria (a 2-hour plasma glucose level of 200 mg/dL or above, following a 75-g glucose load), the OGTT detected 291 individuals (3.3% of 8,696 study participants) with type 2 diabetes.

Among the white Europeans, use of the 6.5% A1c cutoff had a sensitivity of 62% and a positive predictive value of 45%. Based on an Australian study published earlier this year, the investigators chose to compare those values with a rule-out A1c cutoff of 5.5% and a rule-in cutoff of 7.0%, with a confirmatory OGTT used for those falling in between (Diabetes Care 2010;33:817-9).

That method gave an improved sensitivity of 98% and positive predictive value of 76% in the white European group. With either method, specificity and negative predictive values were close to 100%. For the South Asians, the 6.5% cutoff gave a sensitivity of 79% and positive predictive value of 36%, both of which improved to 99% and 68%, respectively, with the two–cut-point criteria. Again, specificity and negative predictive values were strong with either method, Dr. Mostafa reported.

"Impaired HbA1c," the term used for the values between the two cutoffs (5.6%-6.9%), was found in 59% of the total cohort, who thus required confirmatory tests. Noting that those in the impaired HbA1c group (55% of the total cohort) had A1c values between 5.6% and 6.4% (that is, lower than 6.5%), they tried various cut points and arrived at a rule-out value of 5.8% or below and a rule-in value of 6.8% or above. That left 28% of the total cohort in the "impaired HbA1c" category when defined as an A1c of 5.9%-6.7%.

"We believe [a rule-out value of 5.8% and a rule-in value of 6.8%] would be a more feasible strategy to implement in clinical practice," Dr. Mostafa said.

These cutoffs gave sensitivities of 92% for white Europeans and 98% for South Asians, and positive predictive values of 70% and 54%, respectively, while maintaining the nearly 100% specificity and negative predictive values for both ethnic groups. Despite the slight reductions in positive predictive values, "overall, we feel using the cut points of 5.8% and 6.8% is still diagnostically accurate, with the major advantage that only a quarter of the population would have to return for a subsequent test," he said.

In a final analysis, the investigators looked at mean HbA1c values in various undiagnosed populations. Compared with the U.K. cohort’s mean of 5.7%, the Australian cohort had a mean of 5.1%, which resulted in 24% falling into their 5.6%-6.9% "impaired HbA1c" category. That led to the hypothesis that broader cut points are acceptable when mean A1c is relatively low, but a tighter range is required when mean A1c is higher.

Studies conducted in Denmark and in India showed relatively high mean A1c values of 5.8% and 5.6%, respectively, similar to the U.K. group. Those populations would probably need to use narrower cut points to reduce the number of people who would require subsequent testing. In contrast, like the Australians, data from the U.S. National Health and Nutrition Examination Survey showed a 5.2% mean A1c, meaning that a broader cut point range might be feasible, Dr. Mostafa said.

Dr. Mostafa stated that he had no disclosures.

STOCKHOLM – Use of a "rule-in" hemoglobin A1c cut point of 6.8% and a "rule-out" value of 5.8%, with glucose testing for individuals who fall in the middle of the diagnostic cutoff, was more accurate in diagnosing type 2 diabetes than was a single cutoff value of 6.5%.

The finding from a multiethnic cohort study of 8,696 previously undiagnosed primary care patients addresses some of the concerns about false-positive and false-negative diagnoses associated with using a single measure of hemoglobin A1c. Multiple studies have shown that the 6.5% cutoff may be discordant with the results of an oral glucose tolerance test (OGTT), which is considered to be the standard diagnostic test for type 2 diabetes, said Dr. Samiul A. Mostafa, a clinical research fellow in the diabetes research unit of the University of Leicester (England).

In July 2009, an international expert committee recommended the use of hemoglobin A1c for diagnosing diabetes, with a diagnostic cutoff of 6.5% or above following a repeat confirmatory A1c test (Diabetes Care 2009;32:1327-34). In January 2010, the American Diabetes Association endorsed that recommendation (Diabetes Care 2010;33[suppl. 1]:S62-9). The European Association for the Study of Diabetes and the World Health Organization are expected to issue similar statements soon.

The study participants were identified from two systematic screening programs during 2002-2008. Three-quarters (75%) were white Europeans and 23% were South Asians from Pakistan, Bangladesh, and India. The mean A1c for the entire cohort was 5.7%. All underwent an OGTT and also had their HbA1c levels measured. Using the WHO criteria (a 2-hour plasma glucose level of 200 mg/dL or above, following a 75-g glucose load), the OGTT detected 291 individuals (3.3% of 8,696 study participants) with type 2 diabetes.

Among the white Europeans, use of the 6.5% A1c cutoff had a sensitivity of 62% and a positive predictive value of 45%. Based on an Australian study published earlier this year, the investigators chose to compare those values with a rule-out A1c cutoff of 5.5% and a rule-in cutoff of 7.0%, with a confirmatory OGTT used for those falling in between (Diabetes Care 2010;33:817-9).

That method gave an improved sensitivity of 98% and positive predictive value of 76% in the white European group. With either method, specificity and negative predictive values were close to 100%. For the South Asians, the 6.5% cutoff gave a sensitivity of 79% and positive predictive value of 36%, both of which improved to 99% and 68%, respectively, with the two–cut-point criteria. Again, specificity and negative predictive values were strong with either method, Dr. Mostafa reported.

"Impaired HbA1c," the term used for the values between the two cutoffs (5.6%-6.9%), was found in 59% of the total cohort, who thus required confirmatory tests. Noting that those in the impaired HbA1c group (55% of the total cohort) had A1c values between 5.6% and 6.4% (that is, lower than 6.5%), they tried various cut points and arrived at a rule-out value of 5.8% or below and a rule-in value of 6.8% or above. That left 28% of the total cohort in the "impaired HbA1c" category when defined as an A1c of 5.9%-6.7%.

"We believe [a rule-out value of 5.8% and a rule-in value of 6.8%] would be a more feasible strategy to implement in clinical practice," Dr. Mostafa said.

These cutoffs gave sensitivities of 92% for white Europeans and 98% for South Asians, and positive predictive values of 70% and 54%, respectively, while maintaining the nearly 100% specificity and negative predictive values for both ethnic groups. Despite the slight reductions in positive predictive values, "overall, we feel using the cut points of 5.8% and 6.8% is still diagnostically accurate, with the major advantage that only a quarter of the population would have to return for a subsequent test," he said.

In a final analysis, the investigators looked at mean HbA1c values in various undiagnosed populations. Compared with the U.K. cohort’s mean of 5.7%, the Australian cohort had a mean of 5.1%, which resulted in 24% falling into their 5.6%-6.9% "impaired HbA1c" category. That led to the hypothesis that broader cut points are acceptable when mean A1c is relatively low, but a tighter range is required when mean A1c is higher.

Studies conducted in Denmark and in India showed relatively high mean A1c values of 5.8% and 5.6%, respectively, similar to the U.K. group. Those populations would probably need to use narrower cut points to reduce the number of people who would require subsequent testing. In contrast, like the Australians, data from the U.S. National Health and Nutrition Examination Survey showed a 5.2% mean A1c, meaning that a broader cut point range might be feasible, Dr. Mostafa said.

Dr. Mostafa stated that he had no disclosures.

The American Association of Clinical Endocrinologists has issued two consensus panel statements to guide physicians in the use of continuous glucose monitoring.

The continuous glucose monitoring (CGM) statement defines the two types of available devices. With professional CGM, the patient wears the device for 3-5 days but is unaware of the results. The physician subsequently downloads and analyzes the data to guide treatment decisions. Personal CGM devices, in contrast, are owned by the patient, who can see the results in real time. While not approved for “treatment decisions,” the data are used in conjunction with self–blood glucose monitoring to inform medication adjustments.

The document summarizes data from several randomized controlled clinical trials that have evaluated the effects of CGM in the treatment of type 1 diabetes. On the basis of those, AACE recommended personal CGM for the following patient groups:

▸ Those with type 1 diabetes who have hypoglycemic unawareness or frequent hypoglycemia, hemoglobin A_1c over target, or excess glycemic variability, and those who require HbA_1c-lowering without increased hypoglycemia.

▸ Those planning pregnancy or who are pregnant.

▸ Children and adolescents with type 1 diabetes who have achieved HbA_1c levels less than 7.0% (these patients and their families are typically highly motivated), and youth with type 1 diabetes who have HbA_1c levels of at least 7.0% and are able to use the device on a near-daily basis.

In addition, the following patients might be good candidates for personal CGM, and a trial period of 2-4 weeks is recommended:

▸ Youth who frequently monitor their blood glucose levels.

▸ Committed families of young children (younger than 8 years), especially if the patient is having problems with hypoglycemia.

And, AACE advised, intermittent use of professional CGM may be useful for youth with type 1 diabetes who are experiencing changes to their diabetes regimen or have problems with nocturnal hypoglycemia/dawn phenomenon, hypoglycemia unawareness, and/or postprandial hyperglycemia.

The document also provides information about reimbursement for CGM, including advice on coding and a list of selected major U.S. private insurers' policies regarding CGM coverage (or lack thereof). The Centers for Medicare and Medicaid Services currently reimburses only for professional CGM.

That document summarizes the current state of the art with regard to continuous subcutaneous insulin delivery – pumps – noting that appropriate patient selection is critical, along with thorough assessment of their knowledge of diabetes management principles. Further, “selection of a provider is critical, and only those whose practice can assume full responsibility for the comprehensive pump management program should offer it.

“Patient diabetes education and a pump training plan must be implemented by a multidisciplinary team under direction of an experienced endocrinologist/diabetologist to address gaps in patient knowledge, and physicians prescribing insulin pumps for their patients should have a round-the-clock system in place to answer patients' concerns about pump problems,” the AACE statement advises.

Topics addressed include data comparing pump therapy with multiple insulin injections, pump safety data, and cost-effectiveness analyses, along with information on the economic feasibility of using pumps in medical practices. “Hard-core” data from randomized clinical trials published in peer-reviewed journals that provide evidence for the benefits of insulin pump therapy are lacking, AACE noted.

Some, though not all, of the task force authors of both documents disclosed financial relationships with manufacturers of pumps, CGM, and glucose-lowering medications.

Both statements are available online at www.aace.com

The American Association of Clinical Endocrinologists has issued two consensus panel statements to guide physicians in the use of continuous glucose monitoring.

The continuous glucose monitoring (CGM) statement defines the two types of available devices. With professional CGM, the patient wears the device for 3-5 days but is unaware of the results. The physician subsequently downloads and analyzes the data to guide treatment decisions. Personal CGM devices, in contrast, are owned by the patient, who can see the results in real time. While not approved for “treatment decisions,” the data are used in conjunction with self–blood glucose monitoring to inform medication adjustments.

The document summarizes data from several randomized controlled clinical trials that have evaluated the effects of CGM in the treatment of type 1 diabetes. On the basis of those, AACE recommended personal CGM for the following patient groups:

▸ Those with type 1 diabetes who have hypoglycemic unawareness or frequent hypoglycemia, hemoglobin A_1c over target, or excess glycemic variability, and those who require HbA_1c-lowering without increased hypoglycemia.

▸ Those planning pregnancy or who are pregnant.

▸ Children and adolescents with type 1 diabetes who have achieved HbA_1c levels less than 7.0% (these patients and their families are typically highly motivated), and youth with type 1 diabetes who have HbA_1c levels of at least 7.0% and are able to use the device on a near-daily basis.

In addition, the following patients might be good candidates for personal CGM, and a trial period of 2-4 weeks is recommended:

▸ Youth who frequently monitor their blood glucose levels.

▸ Committed families of young children (younger than 8 years), especially if the patient is having problems with hypoglycemia.

And, AACE advised, intermittent use of professional CGM may be useful for youth with type 1 diabetes who are experiencing changes to their diabetes regimen or have problems with nocturnal hypoglycemia/dawn phenomenon, hypoglycemia unawareness, and/or postprandial hyperglycemia.

The document also provides information about reimbursement for CGM, including advice on coding and a list of selected major U.S. private insurers' policies regarding CGM coverage (or lack thereof). The Centers for Medicare and Medicaid Services currently reimburses only for professional CGM.

That document summarizes the current state of the art with regard to continuous subcutaneous insulin delivery – pumps – noting that appropriate patient selection is critical, along with thorough assessment of their knowledge of diabetes management principles. Further, “selection of a provider is critical, and only those whose practice can assume full responsibility for the comprehensive pump management program should offer it.

“Patient diabetes education and a pump training plan must be implemented by a multidisciplinary team under direction of an experienced endocrinologist/diabetologist to address gaps in patient knowledge, and physicians prescribing insulin pumps for their patients should have a round-the-clock system in place to answer patients' concerns about pump problems,” the AACE statement advises.

Topics addressed include data comparing pump therapy with multiple insulin injections, pump safety data, and cost-effectiveness analyses, along with information on the economic feasibility of using pumps in medical practices. “Hard-core” data from randomized clinical trials published in peer-reviewed journals that provide evidence for the benefits of insulin pump therapy are lacking, AACE noted.

Some, though not all, of the task force authors of both documents disclosed financial relationships with manufacturers of pumps, CGM, and glucose-lowering medications.

Both statements are available online at www.aace.com

The American Association of Clinical Endocrinologists has issued two consensus panel statements to guide physicians in the use of continuous glucose monitoring.

The continuous glucose monitoring (CGM) statement defines the two types of available devices. With professional CGM, the patient wears the device for 3-5 days but is unaware of the results. The physician subsequently downloads and analyzes the data to guide treatment decisions. Personal CGM devices, in contrast, are owned by the patient, who can see the results in real time. While not approved for “treatment decisions,” the data are used in conjunction with self–blood glucose monitoring to inform medication adjustments.

The document summarizes data from several randomized controlled clinical trials that have evaluated the effects of CGM in the treatment of type 1 diabetes. On the basis of those, AACE recommended personal CGM for the following patient groups:

▸ Those with type 1 diabetes who have hypoglycemic unawareness or frequent hypoglycemia, hemoglobin A_1c over target, or excess glycemic variability, and those who require HbA_1c-lowering without increased hypoglycemia.

▸ Those planning pregnancy or who are pregnant.

▸ Children and adolescents with type 1 diabetes who have achieved HbA_1c levels less than 7.0% (these patients and their families are typically highly motivated), and youth with type 1 diabetes who have HbA_1c levels of at least 7.0% and are able to use the device on a near-daily basis.

In addition, the following patients might be good candidates for personal CGM, and a trial period of 2-4 weeks is recommended:

▸ Youth who frequently monitor their blood glucose levels.

▸ Committed families of young children (younger than 8 years), especially if the patient is having problems with hypoglycemia.

And, AACE advised, intermittent use of professional CGM may be useful for youth with type 1 diabetes who are experiencing changes to their diabetes regimen or have problems with nocturnal hypoglycemia/dawn phenomenon, hypoglycemia unawareness, and/or postprandial hyperglycemia.

The document also provides information about reimbursement for CGM, including advice on coding and a list of selected major U.S. private insurers' policies regarding CGM coverage (or lack thereof). The Centers for Medicare and Medicaid Services currently reimburses only for professional CGM.

That document summarizes the current state of the art with regard to continuous subcutaneous insulin delivery – pumps – noting that appropriate patient selection is critical, along with thorough assessment of their knowledge of diabetes management principles. Further, “selection of a provider is critical, and only those whose practice can assume full responsibility for the comprehensive pump management program should offer it.

“Patient diabetes education and a pump training plan must be implemented by a multidisciplinary team under direction of an experienced endocrinologist/diabetologist to address gaps in patient knowledge, and physicians prescribing insulin pumps for their patients should have a round-the-clock system in place to answer patients' concerns about pump problems,” the AACE statement advises.

Topics addressed include data comparing pump therapy with multiple insulin injections, pump safety data, and cost-effectiveness analyses, along with information on the economic feasibility of using pumps in medical practices. “Hard-core” data from randomized clinical trials published in peer-reviewed journals that provide evidence for the benefits of insulin pump therapy are lacking, AACE noted.

Some, though not all, of the task force authors of both documents disclosed financial relationships with manufacturers of pumps, CGM, and glucose-lowering medications.

Both statements are available online at www.aace.com

STOCKHOLM – The risk for developing type 2 diabetes is not the same for everyone with metabolic syndrome, but instead varies dramatically depending on individual factors.

In fact, hyperglycemia – with or without metabolic syndrome – was a much stronger predictor of incident type 2 diabetes than was metabolic syndrome without hyperglycemia in a 5-year observational analysis of 58,056 initially nondiabetic adults aged 30 years and older who were members of the managed care organization Kaiser Permanente Northwest, Gregory A. Nichols, Ph.D., said.

“In the absence of impaired fasting glucose, the definition of metabolic syndrome may be a misleading estimator of diabetes risk,” according to Dr. Nichols, the lead investigator on the study (Diabetes Res. Clin. Pract. 2010;90:115-21).

He and a colleague examined the incidence of diabetes for all possible combinations of metabolic syndrome components using criteria defined in the National Cholesterol Education Program's Adult Treatment Panel III report (ATP III) (Circulation 2004;109:433-8). The one exception was the use of body mass index as a substitute for waist circumference, which is rarely measured clinically, noted Dr. Nichols of Kaiser Permanente's Center for Health Research, Portland, Ore.

For the study, an individual was considered to have metabolic syndrome if they met three of the following five criteria: impaired fasting glucose (greater than 100 mg/dL), hypertension (130/85 mm Hg or greater), high triglycerides (150 mg/dL or greater), low HDL cholesterol (less than 40 mg/dL for men, 50 mg/dL for women), and BMI greater than 28.8 kg/m

Over 5 years, 6% of the total study sample developed diabetes. Compared with those who did not develop diabetes, those who did were significantly older (59 vs. 57 years), and were more likely to be male (52% vs. 44%), nonwhite (10% vs. 8%), and a current smoker (15% vs. 12%).

The risk for developing diabetes was greater in the presence than in the absence of each individual component. The 5-year risk for diabetes rose with each component an individual had at baseline, from 0.3% for those with none to 1.2% with one, 3.5% with two, 8.4% with three, 16.9% with four, and 28.2% with five.

Among the five individual components, the greatest diabetes risk was associated with impaired fasting glucose (IFG; incidence of 37.4/1,000 person-years), followed by low HDL cholesterol (21.6/1,000 person-years), high triglycerides (20.6/1,000), obesity (19.5), and hypertension (16.2).

There was a clear separation between combinations of components that did and did not contain IFG. The combination of IFG and any one additional component – by definition, not meeting metabolic syndrome criteria – had a higher incidence rate of diabetes (16.5/1,000 person-years) than did any three- or four-component combination that did not include IFG (7.9 and 11.3 per 1,000 person-years, respectively), yet did meet the metabolic syndrome criteria.

The incidence of diabetes among those who had IFG and no other metabolic syndrome component was 10.2/1,000 person-years, compared with 11.3/1,000 for those with every component except IFG, Dr. Nichols reported.

This study was funded by Tethys Bioscience Inc. Dr. Nichols disclosed that he has received research funding from GlaxoSmithKline, Novartis, Novo Nordisk, Takeda Pharmaceuticals, and Merck.

In the absence of IFG, 'the definition of metabolic syndrome may be a misleading estimator of diabetes risk.'

Source DR. NICHOLS

STOCKHOLM – The risk for developing type 2 diabetes is not the same for everyone with metabolic syndrome, but instead varies dramatically depending on individual factors.

In fact, hyperglycemia – with or without metabolic syndrome – was a much stronger predictor of incident type 2 diabetes than was metabolic syndrome without hyperglycemia in a 5-year observational analysis of 58,056 initially nondiabetic adults aged 30 years and older who were members of the managed care organization Kaiser Permanente Northwest, Gregory A. Nichols, Ph.D., said.

“In the absence of impaired fasting glucose, the definition of metabolic syndrome may be a misleading estimator of diabetes risk,” according to Dr. Nichols, the lead investigator on the study (Diabetes Res. Clin. Pract. 2010;90:115-21).

He and a colleague examined the incidence of diabetes for all possible combinations of metabolic syndrome components using criteria defined in the National Cholesterol Education Program's Adult Treatment Panel III report (ATP III) (Circulation 2004;109:433-8). The one exception was the use of body mass index as a substitute for waist circumference, which is rarely measured clinically, noted Dr. Nichols of Kaiser Permanente's Center for Health Research, Portland, Ore.

For the study, an individual was considered to have metabolic syndrome if they met three of the following five criteria: impaired fasting glucose (greater than 100 mg/dL), hypertension (130/85 mm Hg or greater), high triglycerides (150 mg/dL or greater), low HDL cholesterol (less than 40 mg/dL for men, 50 mg/dL for women), and BMI greater than 28.8 kg/m

Over 5 years, 6% of the total study sample developed diabetes. Compared with those who did not develop diabetes, those who did were significantly older (59 vs. 57 years), and were more likely to be male (52% vs. 44%), nonwhite (10% vs. 8%), and a current smoker (15% vs. 12%).

The risk for developing diabetes was greater in the presence than in the absence of each individual component. The 5-year risk for diabetes rose with each component an individual had at baseline, from 0.3% for those with none to 1.2% with one, 3.5% with two, 8.4% with three, 16.9% with four, and 28.2% with five.

Among the five individual components, the greatest diabetes risk was associated with impaired fasting glucose (IFG; incidence of 37.4/1,000 person-years), followed by low HDL cholesterol (21.6/1,000 person-years), high triglycerides (20.6/1,000), obesity (19.5), and hypertension (16.2).

There was a clear separation between combinations of components that did and did not contain IFG. The combination of IFG and any one additional component – by definition, not meeting metabolic syndrome criteria – had a higher incidence rate of diabetes (16.5/1,000 person-years) than did any three- or four-component combination that did not include IFG (7.9 and 11.3 per 1,000 person-years, respectively), yet did meet the metabolic syndrome criteria.

The incidence of diabetes among those who had IFG and no other metabolic syndrome component was 10.2/1,000 person-years, compared with 11.3/1,000 for those with every component except IFG, Dr. Nichols reported.

This study was funded by Tethys Bioscience Inc. Dr. Nichols disclosed that he has received research funding from GlaxoSmithKline, Novartis, Novo Nordisk, Takeda Pharmaceuticals, and Merck.

In the absence of IFG, 'the definition of metabolic syndrome may be a misleading estimator of diabetes risk.'

Source DR. NICHOLS

STOCKHOLM – The risk for developing type 2 diabetes is not the same for everyone with metabolic syndrome, but instead varies dramatically depending on individual factors.

In fact, hyperglycemia – with or without metabolic syndrome – was a much stronger predictor of incident type 2 diabetes than was metabolic syndrome without hyperglycemia in a 5-year observational analysis of 58,056 initially nondiabetic adults aged 30 years and older who were members of the managed care organization Kaiser Permanente Northwest, Gregory A. Nichols, Ph.D., said.

“In the absence of impaired fasting glucose, the definition of metabolic syndrome may be a misleading estimator of diabetes risk,” according to Dr. Nichols, the lead investigator on the study (Diabetes Res. Clin. Pract. 2010;90:115-21).

He and a colleague examined the incidence of diabetes for all possible combinations of metabolic syndrome components using criteria defined in the National Cholesterol Education Program's Adult Treatment Panel III report (ATP III) (Circulation 2004;109:433-8). The one exception was the use of body mass index as a substitute for waist circumference, which is rarely measured clinically, noted Dr. Nichols of Kaiser Permanente's Center for Health Research, Portland, Ore.

For the study, an individual was considered to have metabolic syndrome if they met three of the following five criteria: impaired fasting glucose (greater than 100 mg/dL), hypertension (130/85 mm Hg or greater), high triglycerides (150 mg/dL or greater), low HDL cholesterol (less than 40 mg/dL for men, 50 mg/dL for women), and BMI greater than 28.8 kg/m

Over 5 years, 6% of the total study sample developed diabetes. Compared with those who did not develop diabetes, those who did were significantly older (59 vs. 57 years), and were more likely to be male (52% vs. 44%), nonwhite (10% vs. 8%), and a current smoker (15% vs. 12%).

The risk for developing diabetes was greater in the presence than in the absence of each individual component. The 5-year risk for diabetes rose with each component an individual had at baseline, from 0.3% for those with none to 1.2% with one, 3.5% with two, 8.4% with three, 16.9% with four, and 28.2% with five.

Among the five individual components, the greatest diabetes risk was associated with impaired fasting glucose (IFG; incidence of 37.4/1,000 person-years), followed by low HDL cholesterol (21.6/1,000 person-years), high triglycerides (20.6/1,000), obesity (19.5), and hypertension (16.2).

There was a clear separation between combinations of components that did and did not contain IFG. The combination of IFG and any one additional component – by definition, not meeting metabolic syndrome criteria – had a higher incidence rate of diabetes (16.5/1,000 person-years) than did any three- or four-component combination that did not include IFG (7.9 and 11.3 per 1,000 person-years, respectively), yet did meet the metabolic syndrome criteria.

The incidence of diabetes among those who had IFG and no other metabolic syndrome component was 10.2/1,000 person-years, compared with 11.3/1,000 for those with every component except IFG, Dr. Nichols reported.

This study was funded by Tethys Bioscience Inc. Dr. Nichols disclosed that he has received research funding from GlaxoSmithKline, Novartis, Novo Nordisk, Takeda Pharmaceuticals, and Merck.

In the absence of IFG, 'the definition of metabolic syndrome may be a misleading estimator of diabetes risk.'

Source DR. NICHOLS

Major Finding: The cumulative incidence of microalbuminuria was 8.2% of patients on olmesartan vs. 9.8% of placebo patients, for a highly significant risk reduction of 23%.

Data Source: Randomized, placebo-controlled, double-blind, multicenter ROADMAP trial of 4,447 patients with type 2 diabetes and one or more other cardiovascular risk factors but with normoalbuminuria.

Disclosures: The study was funded by Daiichi-Sankyo, which manufactures olmesartan under the name Benicar.

STOCKHOLM – Olmesartan significantly reduced the time to microalbuminuria in a randomized, placebo-controlled, double-blind multicenter study of 4,447 patients with type 2 diabetes.

The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) trial investigated whether early treatment with the angiotensin receptor blocker olmesartan would delay the occurrence of microalbuminuria in patients with type 2 diabetes who had at least one other cardiovascular risk factor but who had normal albumin excretion at baseline.

At baseline, the patients had a mean age of 58 years, diabetes duration of 6 years, body mass index of 30 kg/m

In both groups, additional antihypertensive drug treatment other than ARBs or ACE inhibitors was used to reach the target BP of less than 130/80 mm Hg. That goal was reached by 78% of the olmesartan group and 71% of the placebo group by 48 months, Dr. Hermann Haller reported at the meeting.

The cumulative incidence of microalbuminuria was 8.2% in the olmesartan patients vs. 9.8% in the placebo group, giving a highly significant risk reduction of 23%, reported Dr. Haller of Hannover (Germany) Medical School.

Correction for the small differences in blood pressure between the two groups showed that the majority of the effect was BP-independent, he said.

Overall cardiovascular morbidity and mortality rates were low and similar between the two groups, with 4.3% of the olmesartan group and 4.2% of the placebo group experiencing any cardiovascular event or death. Total mortality occurred in 1.2% and 1.7%, respectively. Cardiovascular mortality, however, was higher in the olmesartan group (15 deaths vs. 3 deaths, or 0.7% vs. 0.1%), possibly because of hypotensive episodes in patients with preexisting cardiovascular disease.

There were no adverse effects of olmesartan on hard renal outcomes, Dr. Haller said.

Correction for the small differences in blood pressure between groups showed that most of the effect was BP-independent.

Source DR. HALLER

Major Finding: The cumulative incidence of microalbuminuria was 8.2% of patients on olmesartan vs. 9.8% of placebo patients, for a highly significant risk reduction of 23%.

Data Source: Randomized, placebo-controlled, double-blind, multicenter ROADMAP trial of 4,447 patients with type 2 diabetes and one or more other cardiovascular risk factors but with normoalbuminuria.

Disclosures: The study was funded by Daiichi-Sankyo, which manufactures olmesartan under the name Benicar.

STOCKHOLM – Olmesartan significantly reduced the time to microalbuminuria in a randomized, placebo-controlled, double-blind multicenter study of 4,447 patients with type 2 diabetes.

The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) trial investigated whether early treatment with the angiotensin receptor blocker olmesartan would delay the occurrence of microalbuminuria in patients with type 2 diabetes who had at least one other cardiovascular risk factor but who had normal albumin excretion at baseline.

At baseline, the patients had a mean age of 58 years, diabetes duration of 6 years, body mass index of 30 kg/m

In both groups, additional antihypertensive drug treatment other than ARBs or ACE inhibitors was used to reach the target BP of less than 130/80 mm Hg. That goal was reached by 78% of the olmesartan group and 71% of the placebo group by 48 months, Dr. Hermann Haller reported at the meeting.

The cumulative incidence of microalbuminuria was 8.2% in the olmesartan patients vs. 9.8% in the placebo group, giving a highly significant risk reduction of 23%, reported Dr. Haller of Hannover (Germany) Medical School.

Correction for the small differences in blood pressure between the two groups showed that the majority of the effect was BP-independent, he said.

Overall cardiovascular morbidity and mortality rates were low and similar between the two groups, with 4.3% of the olmesartan group and 4.2% of the placebo group experiencing any cardiovascular event or death. Total mortality occurred in 1.2% and 1.7%, respectively. Cardiovascular mortality, however, was higher in the olmesartan group (15 deaths vs. 3 deaths, or 0.7% vs. 0.1%), possibly because of hypotensive episodes in patients with preexisting cardiovascular disease.

There were no adverse effects of olmesartan on hard renal outcomes, Dr. Haller said.

Correction for the small differences in blood pressure between groups showed that most of the effect was BP-independent.

Source DR. HALLER

Major Finding: The cumulative incidence of microalbuminuria was 8.2% of patients on olmesartan vs. 9.8% of placebo patients, for a highly significant risk reduction of 23%.

Data Source: Randomized, placebo-controlled, double-blind, multicenter ROADMAP trial of 4,447 patients with type 2 diabetes and one or more other cardiovascular risk factors but with normoalbuminuria.

Disclosures: The study was funded by Daiichi-Sankyo, which manufactures olmesartan under the name Benicar.

STOCKHOLM – Olmesartan significantly reduced the time to microalbuminuria in a randomized, placebo-controlled, double-blind multicenter study of 4,447 patients with type 2 diabetes.

The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) trial investigated whether early treatment with the angiotensin receptor blocker olmesartan would delay the occurrence of microalbuminuria in patients with type 2 diabetes who had at least one other cardiovascular risk factor but who had normal albumin excretion at baseline.

At baseline, the patients had a mean age of 58 years, diabetes duration of 6 years, body mass index of 30 kg/m

In both groups, additional antihypertensive drug treatment other than ARBs or ACE inhibitors was used to reach the target BP of less than 130/80 mm Hg. That goal was reached by 78% of the olmesartan group and 71% of the placebo group by 48 months, Dr. Hermann Haller reported at the meeting.

The cumulative incidence of microalbuminuria was 8.2% in the olmesartan patients vs. 9.8% in the placebo group, giving a highly significant risk reduction of 23%, reported Dr. Haller of Hannover (Germany) Medical School.

Correction for the small differences in blood pressure between the two groups showed that the majority of the effect was BP-independent, he said.

Overall cardiovascular morbidity and mortality rates were low and similar between the two groups, with 4.3% of the olmesartan group and 4.2% of the placebo group experiencing any cardiovascular event or death. Total mortality occurred in 1.2% and 1.7%, respectively. Cardiovascular mortality, however, was higher in the olmesartan group (15 deaths vs. 3 deaths, or 0.7% vs. 0.1%), possibly because of hypotensive episodes in patients with preexisting cardiovascular disease.

There were no adverse effects of olmesartan on hard renal outcomes, Dr. Haller said.

Correction for the small differences in blood pressure between groups showed that most of the effect was BP-independent.

Source DR. HALLER

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

Major Finding: Complete headache remission was achieved in 10% of those receiving 15 mL of blood, compared with 32% with 20 mL, and 26% with 30 mL.

Data Source: A 5-year, randomized, double-blind, controlled, multicenter trial involving 121 women with postepidural dural puncture headache.

Disclosures: This study was funded by grants from the Australian Society of Anaesthetists and Abbott Australasia.

SAN ANTONIO — A 20-mL or 30-mL volume of autologous blood was superior to 15 mL in a randomized controlled trial of 121 obstetric patients who requested a therapeutic epidural blood patch for headache after inadvertent dural puncture during epidural insertion.

“We concluded … that an attempt to inject at least 20 mL should be made,” said Dr. Michael Paech, the Winthrop Professor and Chair of Obstetric Anesthesia at the University of Western Australia, Perth.

Although 20 mL is the most commonly used volume for therapeutic epidural blood patch (EBP), some experts have advocated using smaller or larger volumes. A 2002 Cochrane review concluded that “adequately powered, randomized trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache” (Cochrane Database Syst Rev. 2002;(2):CD001791). In a recent update, the Cochrane group still did not recommend prophylactic EBP but concluded that “therapeutic epidural blood patch showed a benefit over conservative treatment, based on the limited available evidence” (Cochrane Database Syst Rev. 2010;(1):CD001791).htttil now, the largest study of therapeutic EBP involved 33 patients, Dr. Paech noted.

The current study took place at 10 international centers between September 2004 and August 2009. The 121 women were randomized to 15 mL, 20 mL or 30 mL of blood, and were stratified by center and by receipt of the EBP at less than or longer than 48 hours after dural puncture. They were placed in the lateral position, injected at a rate of 5 mL per 15 seconds, and remained supine for 2 hours after.

There were no significant differences among the three dosage groups in the composite end point of complete response (resolved within 4 hours with no recurrence) or partial response (severity reduced or recurrence), which was achieved by 61% of the 15-mL group, 73% of the 20-mL group and 67% of the 30-mL group.

However, complete remission with no recurrence was far less common in the 15-mL group, with just 10% achieving that end point, compared with 32% of the 20-mL group and 26% of the 30-mL group. Compared with the 15-mL group, the odds ratios for complete headache relief were 4.7 for 20 mL and 3.6 for 30 mL, Dr. Paech reported.

There were no significant differences among the groups in functional assessment of headache impact, time to return of headache (overall mean 98 hours), time from EBP to hospital discharge, or incidence of repeat EBP. About half of the patients experienced back pain during the EBP injection, while back pain after the EBP occurred in about 85% overall, did not differ significantly among the groups, and was usually of low intensity, he said.

The proportions still suffering from moderate to severe back pain after 5 days did not differ significantly, although it was greater in the 15-mL group at 23%, compared with 12% of the 20-mL group and 11% of the 30-mL group..

During the question-and-answer period, Dr. Paech noted that the odds of partial or complete relief of headache if EBP was performed more than 48 hours (about two-thirds of all the subjects) from the dural puncture was 3.2 times greater than if done within 48 hours, a significant difference.

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT

SAN ANTONIO — Pregnancy-related subarachnoid hemorrhage presented most often in the postpartum period and often with severe headache, analyses of both nationwide and single-institution datasets revealed.

In an analysis of data from the Nationwide Inpatient Sample – an administrative dataset containing information on 20% of United States hospital admissions – SAH occurred at a rate of 5.6 per 100,000 deliveries and 5.0 per 100,000 pregnancy-related admissions. Two-thirds of these occurred in the postpartum period, Dr. Vanessa A. Olbrecht said.

Although rare, the incidence of SAH is increased twofold among women in the intrapartum/peripartum periods compared with the general population, and it is the second leading cause of indirect maternal death after cardiac disease. SAH needs to be considered in the differential diagnosis of postpartum headache, according to Dr. Olbrecht.

She and her associates at Massachusetts General Hospital used two data sources to investigate the epidemiology of SAH in pregnancy. From the NIS, they extracted all pregnancy-related admissions for women aged 15–44 years during 1997–2006, and identified all of those admissions with a primary or secondary diagnosis of SAH.

The second analysis was a comprehensive retrospective review of their own institution's experience with pregnancy-related SAH from 1992 through 2009. Here, they included only patients with SAH as the primary pathology, Dr. Olbrecht explained.

In the NIS, there were an estimated 2,254 cases of pregnancy-related SAH in the United States during the study period.

There was a geometric increase in SAH with age, with a doubling of the incidence from those aged 35–39 years to 40–44 years and odds ratios of 1.7 to 2.3 per every 10-year increase in age.

In a logistic regression analysis, eclampsia was the single biggest predictor of pregnancy-related SAH, with an “impressive” odds ratio of 88.4. Other significant and independent predictors included coagulopathy (odds ratio 7.2), preeclampsia superimposed on preexisting hypertension (4.2), severe preeclampsia (3.1), tobacco use (2.6), pre-existing hypertension (2.4), African-American race (2.4, compared with Caucasians), mild preeclampsia (2.1), and Hispanic race (1.6).

Compared with an age-matched cohort of non-pregnant women with SAH, the pregnant women with SAH had significantly lower in-hospital mortality, with a rate of 10.7% versus 18.7%. The proportion discharged somewhere other than home was 35.2% among the pregnant women with SAH vs. 48% among those with non-pregnancy related SAH. And the percentage who had aneurysm clipping/coiling – used as a proxy for aneurysmal SAH – was 12.1% in the pregnancy-related SAH group, compared with 44.2% among the non-pregnant SAH patients.

At Massachusetts General, there were 11 cases of SAH during the 17-year study period. Nine of the 11 had cesarean sections, and only 2 had vaginal deliveries. The women ranged in age from 19 to 42, with one-third over the age of 35 at the time of diagnosis. Half were Caucasian, 3 were African-American, and 2 were Hispanic. As in the NIS, two-thirds of the SAH occurred in the postpartum period, at a median of postpartum day 8.

The majority (9) presented with a sudden severe headache, and one-fourth (3) had seizures. Three cases were aneurysmal and were treated with craniotomy, and 2 were associated with venous sinus thrombosis. One patient died, and two were discharged home with significant neurologic deficits.

None of the study authors reported having relevant conflicts of interest.

SAH needs to be considered in the differential diagnosis of postpartum headache.

Source DR. OLBRECHT

Major Finding: Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3, but there were no significant differences at 6 weeks in depression or at 1 year in pain or depression.

Data Source: One-year follow-up of 82 parturients from an initial randomized, controlled trial of 188.

Disclosures: None was reported.

SAN ANTONIO — A single postpartum low dose of ketamine significantly and persistently reduced pain for up to 6 weeks after cesarean delivery compared with placebo, but there were no significant differences in chronic pain or depression between the two groups at 1 year, in a randomized, double-blind study of 82 women.

Low doses of the N-methyl-d-aspartate (NMDA) antagonist ketamine have been shown to decrease postoperative opioid requirements, and the drug has also been shown to have an antidepressive effect (Arch. Gen. Psychiatry 2006;63:856–64). hhose data led to the hypothesis that women who receive a single intravenous dose of ketamine might be less likely to develop postpartum depression or chronic pelvic pain, said Dr. Laurie Chalifoux of Northwestern University, Chicago.

A total of 188 women were randomized to receive either 10 mg IV ketamine or saline by a blinded anesthesiologist 5 minutes after cesarean delivery.

All received scheduled IV ketorolac 30 mg every 6 hours for 24 hours, along with 1 or 2 tablets of acetaminophen 325 mg/hydrocodone 10 mg every 4 hours as needed for breakthrough pain.

Among those 188 women, the group who received ketamine reported significantly lower numeric pain rating scores (on a scale of 1–10) than did those receiving saline.

However, there were no differences at any other time point, Dr. Chalifoux reported at the meeting.

The 82 patients who were available for an interview 1 year later were asked to report pain scores (1–10) and whether they had a self-diagnosis of depression at both 6 weeks and 1 year post partum. Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3.

Depression did not differ at 6 weeks, with just one woman (2%) from each group reporting that she was depressed at that point.

At 1 year, pain scores were nearly 0 in both groups and did not differ significantly (0.1 with ketamine vs. 0.0 with saline).

Depression also did not differ significantly, although there were two women (5%) who reported being depressed at 1 year in the saline group compared with none in the ketamine group.

It's possible that a higher dose than 10 mg might have had a greater impact, given that the previous studies showing analgesic and antidepressive effects used doses ranging from 0.15 to 1.0 mg/kg. However, the potential side effects of ketamine – including dysphoria, memory loss, hallucinations, seizures, nystagmus, hypertension, tachycardia, and nausea/vomiting – suggest that dosages should be kept in the lower ranges, Dr. Chalifoux noted.

Also, it's possible that ketamine might not have a large impact among healthy parturients, but it might among those who are at increased risk for depression or chronic pain, she said.

Major Finding: Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3, but there were no significant differences at 6 weeks in depression or at 1 year in pain or depression.

Data Source: One-year follow-up of 82 parturients from an initial randomized, controlled trial of 188.

Disclosures: None was reported.

SAN ANTONIO — A single postpartum low dose of ketamine significantly and persistently reduced pain for up to 6 weeks after cesarean delivery compared with placebo, but there were no significant differences in chronic pain or depression between the two groups at 1 year, in a randomized, double-blind study of 82 women.

Low doses of the N-methyl-d-aspartate (NMDA) antagonist ketamine have been shown to decrease postoperative opioid requirements, and the drug has also been shown to have an antidepressive effect (Arch. Gen. Psychiatry 2006;63:856–64). hhose data led to the hypothesis that women who receive a single intravenous dose of ketamine might be less likely to develop postpartum depression or chronic pelvic pain, said Dr. Laurie Chalifoux of Northwestern University, Chicago.

A total of 188 women were randomized to receive either 10 mg IV ketamine or saline by a blinded anesthesiologist 5 minutes after cesarean delivery.

All received scheduled IV ketorolac 30 mg every 6 hours for 24 hours, along with 1 or 2 tablets of acetaminophen 325 mg/hydrocodone 10 mg every 4 hours as needed for breakthrough pain.

Among those 188 women, the group who received ketamine reported significantly lower numeric pain rating scores (on a scale of 1–10) than did those receiving saline.

However, there were no differences at any other time point, Dr. Chalifoux reported at the meeting.

The 82 patients who were available for an interview 1 year later were asked to report pain scores (1–10) and whether they had a self-diagnosis of depression at both 6 weeks and 1 year post partum. Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3.

Depression did not differ at 6 weeks, with just one woman (2%) from each group reporting that she was depressed at that point.

At 1 year, pain scores were nearly 0 in both groups and did not differ significantly (0.1 with ketamine vs. 0.0 with saline).

Depression also did not differ significantly, although there were two women (5%) who reported being depressed at 1 year in the saline group compared with none in the ketamine group.

It's possible that a higher dose than 10 mg might have had a greater impact, given that the previous studies showing analgesic and antidepressive effects used doses ranging from 0.15 to 1.0 mg/kg. However, the potential side effects of ketamine – including dysphoria, memory loss, hallucinations, seizures, nystagmus, hypertension, tachycardia, and nausea/vomiting – suggest that dosages should be kept in the lower ranges, Dr. Chalifoux noted.

Also, it's possible that ketamine might not have a large impact among healthy parturients, but it might among those who are at increased risk for depression or chronic pain, she said.

Major Finding: Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3, but there were no significant differences at 6 weeks in depression or at 1 year in pain or depression.

Data Source: One-year follow-up of 82 parturients from an initial randomized, controlled trial of 188.

Disclosures: None was reported.

SAN ANTONIO — A single postpartum low dose of ketamine significantly and persistently reduced pain for up to 6 weeks after cesarean delivery compared with placebo, but there were no significant differences in chronic pain or depression between the two groups at 1 year, in a randomized, double-blind study of 82 women.

Low doses of the N-methyl-d-aspartate (NMDA) antagonist ketamine have been shown to decrease postoperative opioid requirements, and the drug has also been shown to have an antidepressive effect (Arch. Gen. Psychiatry 2006;63:856–64). hhose data led to the hypothesis that women who receive a single intravenous dose of ketamine might be less likely to develop postpartum depression or chronic pelvic pain, said Dr. Laurie Chalifoux of Northwestern University, Chicago.

A total of 188 women were randomized to receive either 10 mg IV ketamine or saline by a blinded anesthesiologist 5 minutes after cesarean delivery.

All received scheduled IV ketorolac 30 mg every 6 hours for 24 hours, along with 1 or 2 tablets of acetaminophen 325 mg/hydrocodone 10 mg every 4 hours as needed for breakthrough pain.

Among those 188 women, the group who received ketamine reported significantly lower numeric pain rating scores (on a scale of 1–10) than did those receiving saline.

However, there were no differences at any other time point, Dr. Chalifoux reported at the meeting.

The 82 patients who were available for an interview 1 year later were asked to report pain scores (1–10) and whether they had a self-diagnosis of depression at both 6 weeks and 1 year post partum. Patients in the ketamine group reported significantly less pain at 6 weeks post partum, with scores of 1.3 vs. 2.3.

Depression did not differ at 6 weeks, with just one woman (2%) from each group reporting that she was depressed at that point.

At 1 year, pain scores were nearly 0 in both groups and did not differ significantly (0.1 with ketamine vs. 0.0 with saline).

Depression also did not differ significantly, although there were two women (5%) who reported being depressed at 1 year in the saline group compared with none in the ketamine group.

It's possible that a higher dose than 10 mg might have had a greater impact, given that the previous studies showing analgesic and antidepressive effects used doses ranging from 0.15 to 1.0 mg/kg. However, the potential side effects of ketamine – including dysphoria, memory loss, hallucinations, seizures, nystagmus, hypertension, tachycardia, and nausea/vomiting – suggest that dosages should be kept in the lower ranges, Dr. Chalifoux noted.

Also, it's possible that ketamine might not have a large impact among healthy parturients, but it might among those who are at increased risk for depression or chronic pain, she said.

ATLANTA – A booster dose of meningococcal conjugate vaccine should be given to adolescents at 16 years of age if they received a first dose at age 11-12 years, and a booster should be given 5 years after the first dose – up to age 21 years – to those who first received the vaccine at age 13-15 years.

That was the vote of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention on Oct. 27th, but it was not unanimous. The panel was split 6-5, with 3 abstentions. Following that vote, ACIP also voted to include the booster dose under the federal Vaccines for Children program. The CDC usually adopts the ACIP's recommendations but is not obligated to do so.

In 2007, ACIP recommended that the quadrivalent meningococcal conjugate vaccine (MCV4), sold under the brand names Menactra and Menveo, be given to 11- to 12-year-olds at the established preteen visit, and to 13- to 18-year-olds who had not been previously vaccinated. At that time, it was assumed that this would protect teenagers through the peak age in disease seen in 16- to 21-year-olds, said Dr. Amanda Cohn of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD).

However, recent data have suggested that immunity from the vaccine wanes within 5 years after vaccination, thereby possibly failing to protect those at highest risk, particularly college students living in dorms.

A cost-effectiveness analysis presented at the meeting by Dr. Ismael Ortega-Sanchez, also with the NCIRD, showed that giving just one dose of MCV4 to all 11-year-olds was the least cost-effective of several options the ACIP considered, at $281,000 per quality adjusted life-year (QALY). Giving one dose just to 15-year-olds would cost $121,000/QALY, while giving doses to all 11-year-olds and 16-year-olds – the option chosen – comes to $157,000/QALY.

Despite the emerging evidence that the current practice of giving MCV4 vaccine to 11-to 12-year-olds is not the ideal option, many panel members and audience members expressed concern about removing the recommendation to give the vaccine at that age since it is part of the now-established preadolescent vaccination visit “platform” that also includes human papillomavirus and diphtheria-tetanus-pertussis vaccinations. Moreover, it does protect those aged 11- to 13-years-old against meningococcal disease.

While the evidence is now clear that the level of protective antibody against Neisseria meningitidis drops to suboptimal levels 5 years after receipt of MCV4, the level of disease does not appear to have been affected yet. Indeed, “We are currently at historic low rates of meningococcal disease,” Dr. Cohn said, adding that the ACIP working group's aim was to make a change in order to prevent those rates from rising again.

However, the sizable minority of the panel who opposed the addition of the booster dose for 16-year-olds cited cost and lack of cost-effectiveness. Among them was ACIP member Dr. Lance Chilton. “I'm worried that we don't have data that would support cost-effectiveness of a 2-dose regimen. It's certainly better than the current 11- to 12-year–only vaccination, but to me the cost-effectiveness data don't justify [the vote],” he said in an interview.

Dr. Chilton of the University of New Mexico, Albuquerque, said he would have preferred simply giving MCV4 at mid-adolescence. “I'm in favor of the preadolescent platform, but I don't think that changing the MCV4 to age 15-16 [years] would appreciably diminish that platform. Adding another platform is probably a good idea.”

As CDC employees, Dr. Cohn and Dr. Ortega-Sanchez have no financial conflicts. Dr. Chilton said that he also had no conflicts of interest.

ATLANTA – A booster dose of meningococcal conjugate vaccine should be given to adolescents at 16 years of age if they received a first dose at age 11-12 years, and a booster should be given 5 years after the first dose – up to age 21 years – to those who first received the vaccine at age 13-15 years.

That was the vote of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention on Oct. 27th, but it was not unanimous. The panel was split 6-5, with 3 abstentions. Following that vote, ACIP also voted to include the booster dose under the federal Vaccines for Children program. The CDC usually adopts the ACIP's recommendations but is not obligated to do so.

In 2007, ACIP recommended that the quadrivalent meningococcal conjugate vaccine (MCV4), sold under the brand names Menactra and Menveo, be given to 11- to 12-year-olds at the established preteen visit, and to 13- to 18-year-olds who had not been previously vaccinated. At that time, it was assumed that this would protect teenagers through the peak age in disease seen in 16- to 21-year-olds, said Dr. Amanda Cohn of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD).

However, recent data have suggested that immunity from the vaccine wanes within 5 years after vaccination, thereby possibly failing to protect those at highest risk, particularly college students living in dorms.

A cost-effectiveness analysis presented at the meeting by Dr. Ismael Ortega-Sanchez, also with the NCIRD, showed that giving just one dose of MCV4 to all 11-year-olds was the least cost-effective of several options the ACIP considered, at $281,000 per quality adjusted life-year (QALY). Giving one dose just to 15-year-olds would cost $121,000/QALY, while giving doses to all 11-year-olds and 16-year-olds – the option chosen – comes to $157,000/QALY.

Despite the emerging evidence that the current practice of giving MCV4 vaccine to 11-to 12-year-olds is not the ideal option, many panel members and audience members expressed concern about removing the recommendation to give the vaccine at that age since it is part of the now-established preadolescent vaccination visit “platform” that also includes human papillomavirus and diphtheria-tetanus-pertussis vaccinations. Moreover, it does protect those aged 11- to 13-years-old against meningococcal disease.

While the evidence is now clear that the level of protective antibody against Neisseria meningitidis drops to suboptimal levels 5 years after receipt of MCV4, the level of disease does not appear to have been affected yet. Indeed, “We are currently at historic low rates of meningococcal disease,” Dr. Cohn said, adding that the ACIP working group's aim was to make a change in order to prevent those rates from rising again.

However, the sizable minority of the panel who opposed the addition of the booster dose for 16-year-olds cited cost and lack of cost-effectiveness. Among them was ACIP member Dr. Lance Chilton. “I'm worried that we don't have data that would support cost-effectiveness of a 2-dose regimen. It's certainly better than the current 11- to 12-year–only vaccination, but to me the cost-effectiveness data don't justify [the vote],” he said in an interview.

Dr. Chilton of the University of New Mexico, Albuquerque, said he would have preferred simply giving MCV4 at mid-adolescence. “I'm in favor of the preadolescent platform, but I don't think that changing the MCV4 to age 15-16 [years] would appreciably diminish that platform. Adding another platform is probably a good idea.”

As CDC employees, Dr. Cohn and Dr. Ortega-Sanchez have no financial conflicts. Dr. Chilton said that he also had no conflicts of interest.

ATLANTA – A booster dose of meningococcal conjugate vaccine should be given to adolescents at 16 years of age if they received a first dose at age 11-12 years, and a booster should be given 5 years after the first dose – up to age 21 years – to those who first received the vaccine at age 13-15 years.

That was the vote of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention on Oct. 27th, but it was not unanimous. The panel was split 6-5, with 3 abstentions. Following that vote, ACIP also voted to include the booster dose under the federal Vaccines for Children program. The CDC usually adopts the ACIP's recommendations but is not obligated to do so.

In 2007, ACIP recommended that the quadrivalent meningococcal conjugate vaccine (MCV4), sold under the brand names Menactra and Menveo, be given to 11- to 12-year-olds at the established preteen visit, and to 13- to 18-year-olds who had not been previously vaccinated. At that time, it was assumed that this would protect teenagers through the peak age in disease seen in 16- to 21-year-olds, said Dr. Amanda Cohn of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD).

However, recent data have suggested that immunity from the vaccine wanes within 5 years after vaccination, thereby possibly failing to protect those at highest risk, particularly college students living in dorms.

A cost-effectiveness analysis presented at the meeting by Dr. Ismael Ortega-Sanchez, also with the NCIRD, showed that giving just one dose of MCV4 to all 11-year-olds was the least cost-effective of several options the ACIP considered, at $281,000 per quality adjusted life-year (QALY). Giving one dose just to 15-year-olds would cost $121,000/QALY, while giving doses to all 11-year-olds and 16-year-olds – the option chosen – comes to $157,000/QALY.

Despite the emerging evidence that the current practice of giving MCV4 vaccine to 11-to 12-year-olds is not the ideal option, many panel members and audience members expressed concern about removing the recommendation to give the vaccine at that age since it is part of the now-established preadolescent vaccination visit “platform” that also includes human papillomavirus and diphtheria-tetanus-pertussis vaccinations. Moreover, it does protect those aged 11- to 13-years-old against meningococcal disease.

While the evidence is now clear that the level of protective antibody against Neisseria meningitidis drops to suboptimal levels 5 years after receipt of MCV4, the level of disease does not appear to have been affected yet. Indeed, “We are currently at historic low rates of meningococcal disease,” Dr. Cohn said, adding that the ACIP working group's aim was to make a change in order to prevent those rates from rising again.

However, the sizable minority of the panel who opposed the addition of the booster dose for 16-year-olds cited cost and lack of cost-effectiveness. Among them was ACIP member Dr. Lance Chilton. “I'm worried that we don't have data that would support cost-effectiveness of a 2-dose regimen. It's certainly better than the current 11- to 12-year–only vaccination, but to me the cost-effectiveness data don't justify [the vote],” he said in an interview.

Dr. Chilton of the University of New Mexico, Albuquerque, said he would have preferred simply giving MCV4 at mid-adolescence. “I'm in favor of the preadolescent platform, but I don't think that changing the MCV4 to age 15-16 [years] would appreciably diminish that platform. Adding another platform is probably a good idea.”

As CDC employees, Dr. Cohn and Dr. Ortega-Sanchez have no financial conflicts. Dr. Chilton said that he also had no conflicts of interest.

Major Finding: The excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age.

Data Source: Several different sources, including the CDC, Merck, and GlaxoSmithKline.

Disclosures: Dr. Cortese and Dr. Baggs are CDC employees and do not have financial disclosures.

ATLANTA – New data on the rotavirus vaccine suggest a slightly increased risk for intussusception following the first dose, but consensus among experts remains that in most cases the vaccine's benefits outweigh the possible risk.

At the meeting, speakers summarized postmarketing surveillance data from Mexico, Brazil, Australia, and the United States for Merck's Rotateq and GlaxoSmithKline's Rotarix. Taken together, the data suggest that the excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age. In contrast, the risk was 1 in 10,000 with Wyeth-Lederle's RotaShield, which was removed from the market in 1999, said Dr. Margaret M. Cortese of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention.

On Sept. 22, 2010, the U.S. Food and Drug Administration approved a label change for Rotarix advising of new data regarding intussusception from an evaluation in Mexico by GSK.

For its part, ACIP will revise the wording of its 2009 rotavirus recommendations only with regard to infants with a previous history of intussusception. Whereas it had previously said that “practitioners should consider the potential risks and benefits of administering rotavirus vaccine” to such infants, the new wording will say that “under usual circumstances in the United States, for infants with a history of intussusception, ACIP considers the possible increased risk of intussusception following rotavirus vaccine to outweigh the benefit of protection against severe rotavirus disease.”

However, “providers may administer rotavirus vaccine” to such an infant “if, in a particular circumstance, they believe the benefit to outweigh the possible risk.”

Data from the different studies were somewhat conflicting. For Rotateq, the incidence rate ratios for intussusception within 7 days of vaccination were 2.8, compared with infants receiving diphtheria, tetanus, and acellular pertussis (DTaP) vaccine in a surveillance study conducted by Merck and 5.26 compared with historical controls in Australian postlicensure surveillance. However, data from the Vaccine Safety Datalink in the United States showed a reduced rate of intussusception with Rotateq, with a ratio of 0.65 compared with infants who did not receive the vaccine, Dr. James Baggs of the CDC's National Center for Emerging and Zoonotic Infectious Diseases reported.

For Rotarix, the risk ratios were 1.8 within 30 days of vaccination from GSK's self-controlled case series, 4.6 within 7 days of vaccination in Mexico, and 1.1 in Brazil, in self- and case-controlled data collected by the CDC and the Pan American Health Organization, and 3.45 from the Australian study, which was based on just five intussusception cases within 7 days of vaccination.

At the same time, the numbers of hospitalizations for gastroenteritis overall and of gastroenteritis due to rotavirus have been declining, with just 4% of 101 gastroenteritis hospitalizations confirmed as rotavirus so far in 2010, down from 26% of 168 cases in 2009 and 51% of 211 cases in 2006, Dr. Cortese said.

Previous data suggested that the vaccine prevents 88% of rotavirus hospitalizations/deaths, 84% of emergency department visits, and 80% of clinic visits. (The numbers are based on updated inputs to the model published in Pediatrics 2007;119:684-97.) Using those numbers, the CDC estimates that in 2009, rotavirus vaccination prevented 295,822 clinic visits, 169,431 emergency department visits, 52,802 hospitalizations, and 16 deaths. “The vaccine has had a significant impact on rotavirus disease in the United States,” Dr. Cortese commented.

Assuming a relative risk of 4.6 for excess intussusception cases for one vaccinated birth cohort through 5 years of age, the vaccine prevents 1,100 hospitalizations and 80 deaths for every one case of intussusception, she said.

In a statementhposted online after the ACIP meeting, the CDC said, “Considering that the data currently available suggest a small risk of intussusception caused by rotavirus vaccine is possible and considering that the benefits of rotavirus vaccination are great, the CDC continues to recommend both Rotarix and RotaTeq to prevent severe rotavirus disease in U.S. infants and children. The CDC will continue to monitor additional data on intussusception as they become available.”

Major Finding: The excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age.

Data Source: Several different sources, including the CDC, Merck, and GlaxoSmithKline.

Disclosures: Dr. Cortese and Dr. Baggs are CDC employees and do not have financial disclosures.

ATLANTA – New data on the rotavirus vaccine suggest a slightly increased risk for intussusception following the first dose, but consensus among experts remains that in most cases the vaccine's benefits outweigh the possible risk.

At the meeting, speakers summarized postmarketing surveillance data from Mexico, Brazil, Australia, and the United States for Merck's Rotateq and GlaxoSmithKline's Rotarix. Taken together, the data suggest that the excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age. In contrast, the risk was 1 in 10,000 with Wyeth-Lederle's RotaShield, which was removed from the market in 1999, said Dr. Margaret M. Cortese of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention.

On Sept. 22, 2010, the U.S. Food and Drug Administration approved a label change for Rotarix advising of new data regarding intussusception from an evaluation in Mexico by GSK.

For its part, ACIP will revise the wording of its 2009 rotavirus recommendations only with regard to infants with a previous history of intussusception. Whereas it had previously said that “practitioners should consider the potential risks and benefits of administering rotavirus vaccine” to such infants, the new wording will say that “under usual circumstances in the United States, for infants with a history of intussusception, ACIP considers the possible increased risk of intussusception following rotavirus vaccine to outweigh the benefit of protection against severe rotavirus disease.”

However, “providers may administer rotavirus vaccine” to such an infant “if, in a particular circumstance, they believe the benefit to outweigh the possible risk.”

Data from the different studies were somewhat conflicting. For Rotateq, the incidence rate ratios for intussusception within 7 days of vaccination were 2.8, compared with infants receiving diphtheria, tetanus, and acellular pertussis (DTaP) vaccine in a surveillance study conducted by Merck and 5.26 compared with historical controls in Australian postlicensure surveillance. However, data from the Vaccine Safety Datalink in the United States showed a reduced rate of intussusception with Rotateq, with a ratio of 0.65 compared with infants who did not receive the vaccine, Dr. James Baggs of the CDC's National Center for Emerging and Zoonotic Infectious Diseases reported.

For Rotarix, the risk ratios were 1.8 within 30 days of vaccination from GSK's self-controlled case series, 4.6 within 7 days of vaccination in Mexico, and 1.1 in Brazil, in self- and case-controlled data collected by the CDC and the Pan American Health Organization, and 3.45 from the Australian study, which was based on just five intussusception cases within 7 days of vaccination.

At the same time, the numbers of hospitalizations for gastroenteritis overall and of gastroenteritis due to rotavirus have been declining, with just 4% of 101 gastroenteritis hospitalizations confirmed as rotavirus so far in 2010, down from 26% of 168 cases in 2009 and 51% of 211 cases in 2006, Dr. Cortese said.

Previous data suggested that the vaccine prevents 88% of rotavirus hospitalizations/deaths, 84% of emergency department visits, and 80% of clinic visits. (The numbers are based on updated inputs to the model published in Pediatrics 2007;119:684-97.) Using those numbers, the CDC estimates that in 2009, rotavirus vaccination prevented 295,822 clinic visits, 169,431 emergency department visits, 52,802 hospitalizations, and 16 deaths. “The vaccine has had a significant impact on rotavirus disease in the United States,” Dr. Cortese commented.

Assuming a relative risk of 4.6 for excess intussusception cases for one vaccinated birth cohort through 5 years of age, the vaccine prevents 1,100 hospitalizations and 80 deaths for every one case of intussusception, she said.

In a statementhposted online after the ACIP meeting, the CDC said, “Considering that the data currently available suggest a small risk of intussusception caused by rotavirus vaccine is possible and considering that the benefits of rotavirus vaccination are great, the CDC continues to recommend both Rotarix and RotaTeq to prevent severe rotavirus disease in U.S. infants and children. The CDC will continue to monitor additional data on intussusception as they become available.”

Major Finding: The excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age.

Data Source: Several different sources, including the CDC, Merck, and GlaxoSmithKline.

Disclosures: Dr. Cortese and Dr. Baggs are CDC employees and do not have financial disclosures.

ATLANTA – New data on the rotavirus vaccine suggest a slightly increased risk for intussusception following the first dose, but consensus among experts remains that in most cases the vaccine's benefits outweigh the possible risk.

At the meeting, speakers summarized postmarketing surveillance data from Mexico, Brazil, Australia, and the United States for Merck's Rotateq and GlaxoSmithKline's Rotarix. Taken together, the data suggest that the excess risk for intussusception is approximately 1 per 97,000 infants following a first dose of rotavirus vaccine given at 6-14 weeks of age. In contrast, the risk was 1 in 10,000 with Wyeth-Lederle's RotaShield, which was removed from the market in 1999, said Dr. Margaret M. Cortese of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention.

On Sept. 22, 2010, the U.S. Food and Drug Administration approved a label change for Rotarix advising of new data regarding intussusception from an evaluation in Mexico by GSK.

For its part, ACIP will revise the wording of its 2009 rotavirus recommendations only with regard to infants with a previous history of intussusception. Whereas it had previously said that “practitioners should consider the potential risks and benefits of administering rotavirus vaccine” to such infants, the new wording will say that “under usual circumstances in the United States, for infants with a history of intussusception, ACIP considers the possible increased risk of intussusception following rotavirus vaccine to outweigh the benefit of protection against severe rotavirus disease.”

However, “providers may administer rotavirus vaccine” to such an infant “if, in a particular circumstance, they believe the benefit to outweigh the possible risk.”

Data from the different studies were somewhat conflicting. For Rotateq, the incidence rate ratios for intussusception within 7 days of vaccination were 2.8, compared with infants receiving diphtheria, tetanus, and acellular pertussis (DTaP) vaccine in a surveillance study conducted by Merck and 5.26 compared with historical controls in Australian postlicensure surveillance. However, data from the Vaccine Safety Datalink in the United States showed a reduced rate of intussusception with Rotateq, with a ratio of 0.65 compared with infants who did not receive the vaccine, Dr. James Baggs of the CDC's National Center for Emerging and Zoonotic Infectious Diseases reported.

For Rotarix, the risk ratios were 1.8 within 30 days of vaccination from GSK's self-controlled case series, 4.6 within 7 days of vaccination in Mexico, and 1.1 in Brazil, in self- and case-controlled data collected by the CDC and the Pan American Health Organization, and 3.45 from the Australian study, which was based on just five intussusception cases within 7 days of vaccination.

At the same time, the numbers of hospitalizations for gastroenteritis overall and of gastroenteritis due to rotavirus have been declining, with just 4% of 101 gastroenteritis hospitalizations confirmed as rotavirus so far in 2010, down from 26% of 168 cases in 2009 and 51% of 211 cases in 2006, Dr. Cortese said.

Previous data suggested that the vaccine prevents 88% of rotavirus hospitalizations/deaths, 84% of emergency department visits, and 80% of clinic visits. (The numbers are based on updated inputs to the model published in Pediatrics 2007;119:684-97.) Using those numbers, the CDC estimates that in 2009, rotavirus vaccination prevented 295,822 clinic visits, 169,431 emergency department visits, 52,802 hospitalizations, and 16 deaths. “The vaccine has had a significant impact on rotavirus disease in the United States,” Dr. Cortese commented.

Assuming a relative risk of 4.6 for excess intussusception cases for one vaccinated birth cohort through 5 years of age, the vaccine prevents 1,100 hospitalizations and 80 deaths for every one case of intussusception, she said.

In a statementhposted online after the ACIP meeting, the CDC said, “Considering that the data currently available suggest a small risk of intussusception caused by rotavirus vaccine is possible and considering that the benefits of rotavirus vaccination are great, the CDC continues to recommend both Rotarix and RotaTeq to prevent severe rotavirus disease in U.S. infants and children. The CDC will continue to monitor additional data on intussusception as they become available.”

ATLANTA – In the face of an ongoing pertussis outbreak in California, a series of three votes by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices aimed to expand and clarify recommendations for pertussis vaccination.

The votes taken at the meeting removed previous language restricting the interval for receipt of the adolescent-adult formulation of the tetanus-diphtheria-pertussis vaccine, and expanded the use of Tdap to adults aged 65 years and older and to undervaccinated children aged 7-10 years.

Kathleen Harriman, Ph.D., of the California Department of Public Health's Immunization Branch updated the committee on the California outbreak. A total of 6,978 cases had been reported as of Oct. 19, 2010, for a rate of 16 cases per 100,000 population. Ten deaths have been reported among infants aged 2 months or younger.

The California state health department has recommended Tdap for all individuals aged 10 years and older who have not yet received it – particularly women of childbearing age (including those who are pregnant), others who have contact with young infants, and individuals older than 64 years of age – and also as a replacement for the old tetanus-diphtheria (Td) vaccine for wound management, even though the vaccine is not licensed for those aged 7-9 years or 64 years and older. The state also said that Tdap should be given without regard to the interval since the previous Td dose, said Dr. Harriman, who is also a registered nurse.

Dr. Jennifer Liang of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD) presented similar draft document language for the ACIP to vote on. In 2005, the ACIP adolescent recommendation (for those aged 11-12 years) had said that an interval of at least 5 years between Td and Tdap was “encouraged” to reduce the risk for local and systemic reactions, particularly the limb swelling that – although usually benign – can be frightening for parents.

The new language, unanimously approved by ACIP (with one abstention), says that adolescents aged 11-18 years who have completed the recommended five-dose childhood diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP)/diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series and adults age 19-64 years should receive a single dose of Tdap in place of one Td dose. Adolescents should receive Tdap at a preventive care visit at 11-12 years of age, Dr. Liang said.

In addition, adolescents or adults who have not received a dose of Tdap – or for whom the status is unknown – should be immunized as soon as feasible, regardless of the interval since the last tetanus- or diphtheria-containing vaccine.

The second vote, to recommend Tdap for adults aged 65 years and older, was taken following presentations by Dr. Wayde Weston of GlaxoSmithKline and Dr. Michael Decker of Sanofi Pasteur, demonstrating immunogenicity and safety of Boostrix and Adacel, respectively, in adults aged 64 and older. GSK has filed an application with the Food and Drug Administration for an indication in that age group; Sanofi Pasteur is working on its application.

The recommendation says that adults aged 65 years and older who have or who anticipate having close contact with an infant aged younger than 12 months (such as a grandparent, child care provider, or health care provider) should receive a single dose of Tdap to protect against pertussis and to reduce the likelihood of transmission of pertussis to infants aged younger than 12 months (who are not yet fully immunized).

In addition, for adults aged 65 and older, a single dose of Tdap vaccine may be given in place of a Td vaccine in those who have not previously received Tdap.

Finally, the committee voted another off-label use of Tdap in children aged 7-10 years with incomplete or unknown pertussis vaccine history. For those children, a single dose of Tdap is recommended to protect against pertussis. If further doses of tetanus- and diphtheria-containing vaccines are needed, then children aged 7-10 years should be vaccinated according to catch-up guidance. Further guidance is forthcoming regarding revaccination.

Children aged 7-10 years who have never been vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccine status should receive a series of three vaccinations containing tetanus and diphtheria toxoids.

The preferred schedule is a single dose of Tdap, followed by a dose of Td more than 4 weeks after Tdap and another dose of Td 6-12 months later. If not given as the first dose, Tdap can be substituted for any of the other Td doses in the series.

Although the California pertussis outbreak has raised the urgency of these recommendations, the ACIP has actually been working on increasing pertussis immunization for at least 2 years, working group chair Dr. Mark H. Sawyer said in an interview.

“The main idea of all of this is to free up people's ability to receive vaccine in special circumstances, such as an outbreak. … But this was already on our agenda. Pertussis has been a recognized problem for some time now. The California outbreak just illuminated its importance. But it's not unique to California. Other states are having significant problems with pertussis,” said Dr. Sawyer, professor of pediatrics at the University of California, San Diego.

As a CDC employee, Dr. Liang has no financial conflicts. Dr. Harriman and Dr. Sawyer also stated that they had no financial conflicts.

ATLANTA – In the face of an ongoing pertussis outbreak in California, a series of three votes by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices aimed to expand and clarify recommendations for pertussis vaccination.

The votes taken at the meeting removed previous language restricting the interval for receipt of the adolescent-adult formulation of the tetanus-diphtheria-pertussis vaccine, and expanded the use of Tdap to adults aged 65 years and older and to undervaccinated children aged 7-10 years.

Kathleen Harriman, Ph.D., of the California Department of Public Health's Immunization Branch updated the committee on the California outbreak. A total of 6,978 cases had been reported as of Oct. 19, 2010, for a rate of 16 cases per 100,000 population. Ten deaths have been reported among infants aged 2 months or younger.

The California state health department has recommended Tdap for all individuals aged 10 years and older who have not yet received it – particularly women of childbearing age (including those who are pregnant), others who have contact with young infants, and individuals older than 64 years of age – and also as a replacement for the old tetanus-diphtheria (Td) vaccine for wound management, even though the vaccine is not licensed for those aged 7-9 years or 64 years and older. The state also said that Tdap should be given without regard to the interval since the previous Td dose, said Dr. Harriman, who is also a registered nurse.

Dr. Jennifer Liang of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD) presented similar draft document language for the ACIP to vote on. In 2005, the ACIP adolescent recommendation (for those aged 11-12 years) had said that an interval of at least 5 years between Td and Tdap was “encouraged” to reduce the risk for local and systemic reactions, particularly the limb swelling that – although usually benign – can be frightening for parents.

The new language, unanimously approved by ACIP (with one abstention), says that adolescents aged 11-18 years who have completed the recommended five-dose childhood diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP)/diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series and adults age 19-64 years should receive a single dose of Tdap in place of one Td dose. Adolescents should receive Tdap at a preventive care visit at 11-12 years of age, Dr. Liang said.

In addition, adolescents or adults who have not received a dose of Tdap – or for whom the status is unknown – should be immunized as soon as feasible, regardless of the interval since the last tetanus- or diphtheria-containing vaccine.

The second vote, to recommend Tdap for adults aged 65 years and older, was taken following presentations by Dr. Wayde Weston of GlaxoSmithKline and Dr. Michael Decker of Sanofi Pasteur, demonstrating immunogenicity and safety of Boostrix and Adacel, respectively, in adults aged 64 and older. GSK has filed an application with the Food and Drug Administration for an indication in that age group; Sanofi Pasteur is working on its application.

The recommendation says that adults aged 65 years and older who have or who anticipate having close contact with an infant aged younger than 12 months (such as a grandparent, child care provider, or health care provider) should receive a single dose of Tdap to protect against pertussis and to reduce the likelihood of transmission of pertussis to infants aged younger than 12 months (who are not yet fully immunized).

In addition, for adults aged 65 and older, a single dose of Tdap vaccine may be given in place of a Td vaccine in those who have not previously received Tdap.

Finally, the committee voted another off-label use of Tdap in children aged 7-10 years with incomplete or unknown pertussis vaccine history. For those children, a single dose of Tdap is recommended to protect against pertussis. If further doses of tetanus- and diphtheria-containing vaccines are needed, then children aged 7-10 years should be vaccinated according to catch-up guidance. Further guidance is forthcoming regarding revaccination.

Children aged 7-10 years who have never been vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccine status should receive a series of three vaccinations containing tetanus and diphtheria toxoids.

The preferred schedule is a single dose of Tdap, followed by a dose of Td more than 4 weeks after Tdap and another dose of Td 6-12 months later. If not given as the first dose, Tdap can be substituted for any of the other Td doses in the series.

Although the California pertussis outbreak has raised the urgency of these recommendations, the ACIP has actually been working on increasing pertussis immunization for at least 2 years, working group chair Dr. Mark H. Sawyer said in an interview.

“The main idea of all of this is to free up people's ability to receive vaccine in special circumstances, such as an outbreak. … But this was already on our agenda. Pertussis has been a recognized problem for some time now. The California outbreak just illuminated its importance. But it's not unique to California. Other states are having significant problems with pertussis,” said Dr. Sawyer, professor of pediatrics at the University of California, San Diego.

As a CDC employee, Dr. Liang has no financial conflicts. Dr. Harriman and Dr. Sawyer also stated that they had no financial conflicts.

ATLANTA – In the face of an ongoing pertussis outbreak in California, a series of three votes by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices aimed to expand and clarify recommendations for pertussis vaccination.

The votes taken at the meeting removed previous language restricting the interval for receipt of the adolescent-adult formulation of the tetanus-diphtheria-pertussis vaccine, and expanded the use of Tdap to adults aged 65 years and older and to undervaccinated children aged 7-10 years.

Kathleen Harriman, Ph.D., of the California Department of Public Health's Immunization Branch updated the committee on the California outbreak. A total of 6,978 cases had been reported as of Oct. 19, 2010, for a rate of 16 cases per 100,000 population. Ten deaths have been reported among infants aged 2 months or younger.

The California state health department has recommended Tdap for all individuals aged 10 years and older who have not yet received it – particularly women of childbearing age (including those who are pregnant), others who have contact with young infants, and individuals older than 64 years of age – and also as a replacement for the old tetanus-diphtheria (Td) vaccine for wound management, even though the vaccine is not licensed for those aged 7-9 years or 64 years and older. The state also said that Tdap should be given without regard to the interval since the previous Td dose, said Dr. Harriman, who is also a registered nurse.

Dr. Jennifer Liang of the CDC's National Center for Immunization and Respiratory Diseases (NCIRD) presented similar draft document language for the ACIP to vote on. In 2005, the ACIP adolescent recommendation (for those aged 11-12 years) had said that an interval of at least 5 years between Td and Tdap was “encouraged” to reduce the risk for local and systemic reactions, particularly the limb swelling that – although usually benign – can be frightening for parents.

The new language, unanimously approved by ACIP (with one abstention), says that adolescents aged 11-18 years who have completed the recommended five-dose childhood diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP)/diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series and adults age 19-64 years should receive a single dose of Tdap in place of one Td dose. Adolescents should receive Tdap at a preventive care visit at 11-12 years of age, Dr. Liang said.

In addition, adolescents or adults who have not received a dose of Tdap – or for whom the status is unknown – should be immunized as soon as feasible, regardless of the interval since the last tetanus- or diphtheria-containing vaccine.

The second vote, to recommend Tdap for adults aged 65 years and older, was taken following presentations by Dr. Wayde Weston of GlaxoSmithKline and Dr. Michael Decker of Sanofi Pasteur, demonstrating immunogenicity and safety of Boostrix and Adacel, respectively, in adults aged 64 and older. GSK has filed an application with the Food and Drug Administration for an indication in that age group; Sanofi Pasteur is working on its application.

The recommendation says that adults aged 65 years and older who have or who anticipate having close contact with an infant aged younger than 12 months (such as a grandparent, child care provider, or health care provider) should receive a single dose of Tdap to protect against pertussis and to reduce the likelihood of transmission of pertussis to infants aged younger than 12 months (who are not yet fully immunized).

In addition, for adults aged 65 and older, a single dose of Tdap vaccine may be given in place of a Td vaccine in those who have not previously received Tdap.

Finally, the committee voted another off-label use of Tdap in children aged 7-10 years with incomplete or unknown pertussis vaccine history. For those children, a single dose of Tdap is recommended to protect against pertussis. If further doses of tetanus- and diphtheria-containing vaccines are needed, then children aged 7-10 years should be vaccinated according to catch-up guidance. Further guidance is forthcoming regarding revaccination.

Children aged 7-10 years who have never been vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccine status should receive a series of three vaccinations containing tetanus and diphtheria toxoids.

The preferred schedule is a single dose of Tdap, followed by a dose of Td more than 4 weeks after Tdap and another dose of Td 6-12 months later. If not given as the first dose, Tdap can be substituted for any of the other Td doses in the series.

Although the California pertussis outbreak has raised the urgency of these recommendations, the ACIP has actually been working on increasing pertussis immunization for at least 2 years, working group chair Dr. Mark H. Sawyer said in an interview.

“The main idea of all of this is to free up people's ability to receive vaccine in special circumstances, such as an outbreak. … But this was already on our agenda. Pertussis has been a recognized problem for some time now. The California outbreak just illuminated its importance. But it's not unique to California. Other states are having significant problems with pertussis,” said Dr. Sawyer, professor of pediatrics at the University of California, San Diego.

As a CDC employee, Dr. Liang has no financial conflicts. Dr. Harriman and Dr. Sawyer also stated that they had no financial conflicts.