Miriam E. Tucker

The Food and Drug Administration has issued an advisory about stolen vials of Levemir that have now resurfaced.

Three separate lots totaling approximately 129,000 10-mL vials of the long-acting basal insulin analogue, made by Novo Nordisk, were stolen in North Carolina and are now being sold in the U.S. market. Some vials from one of the lots were discovered at a medical center in Houston.

These stolen insulin vials may not have been stored or handled properly and may be dangerous to patients. The FDA has received one report of a patient who suffered an adverse event due to poor glucose control after using a vial from one of the lots.

The agency advises the following for patients who use Levemir:

▸ Determine if you have Levemir from one of the following lots: XZF0036, XZF0037, or XZF0038. Lot numbers are located on the side of the box of insulin and also on the side of the vial.

▸ If the Levemir is from one of these lots, replace it with a vial of Levemir from another lot. Do not switch to a different brand of insulin without first contacting your health care provider, because another insulin product may require dosing adjustments.

▸ Always visually inspect your insulin before using it. Levemir is a clear and colorless solution.

▸ Contact the Novo Nordisk Customer Care Center at 800-727-6500 for instructions on what to do with vials from these lots, or if you have any other questions.

“The safety of our patients is of paramount concern and we are working with our partners, the pharmacy, the FDA, and law enforcement authorities to investigate the situation and take immediate steps to maintain the highest standard of safety and quality for our products,” Novo Nordisk said in a statement.

The Food and Drug Administration has issued an advisory about stolen vials of Levemir that have now resurfaced.

Three separate lots totaling approximately 129,000 10-mL vials of the long-acting basal insulin analogue, made by Novo Nordisk, were stolen in North Carolina and are now being sold in the U.S. market. Some vials from one of the lots were discovered at a medical center in Houston.

These stolen insulin vials may not have been stored or handled properly and may be dangerous to patients. The FDA has received one report of a patient who suffered an adverse event due to poor glucose control after using a vial from one of the lots.

The agency advises the following for patients who use Levemir:

▸ Determine if you have Levemir from one of the following lots: XZF0036, XZF0037, or XZF0038. Lot numbers are located on the side of the box of insulin and also on the side of the vial.

▸ If the Levemir is from one of these lots, replace it with a vial of Levemir from another lot. Do not switch to a different brand of insulin without first contacting your health care provider, because another insulin product may require dosing adjustments.

▸ Always visually inspect your insulin before using it. Levemir is a clear and colorless solution.

▸ Contact the Novo Nordisk Customer Care Center at 800-727-6500 for instructions on what to do with vials from these lots, or if you have any other questions.

“The safety of our patients is of paramount concern and we are working with our partners, the pharmacy, the FDA, and law enforcement authorities to investigate the situation and take immediate steps to maintain the highest standard of safety and quality for our products,” Novo Nordisk said in a statement.

The Food and Drug Administration has issued an advisory about stolen vials of Levemir that have now resurfaced.

Three separate lots totaling approximately 129,000 10-mL vials of the long-acting basal insulin analogue, made by Novo Nordisk, were stolen in North Carolina and are now being sold in the U.S. market. Some vials from one of the lots were discovered at a medical center in Houston.

These stolen insulin vials may not have been stored or handled properly and may be dangerous to patients. The FDA has received one report of a patient who suffered an adverse event due to poor glucose control after using a vial from one of the lots.

The agency advises the following for patients who use Levemir:

▸ Determine if you have Levemir from one of the following lots: XZF0036, XZF0037, or XZF0038. Lot numbers are located on the side of the box of insulin and also on the side of the vial.

▸ If the Levemir is from one of these lots, replace it with a vial of Levemir from another lot. Do not switch to a different brand of insulin without first contacting your health care provider, because another insulin product may require dosing adjustments.

▸ Always visually inspect your insulin before using it. Levemir is a clear and colorless solution.

▸ Contact the Novo Nordisk Customer Care Center at 800-727-6500 for instructions on what to do with vials from these lots, or if you have any other questions.

“The safety of our patients is of paramount concern and we are working with our partners, the pharmacy, the FDA, and law enforcement authorities to investigate the situation and take immediate steps to maintain the highest standard of safety and quality for our products,” Novo Nordisk said in a statement.

NEW ORLEANS — Among patients with established cardiovascular disease, diabetes increased the risk for secondary cardiovascular hospitalization or death by 42% in a prospective analysis of data from more than 12,000 members of Kaiser Permanente Northwest.

That increased risk was seen after adjustment for a wide range of risk factors associated with cardiovascular events, and in the setting of relatively high use of guideline-recommended medications for secondary prevention.

“Cardiovascular disease prevention in patients with diabetes remains the Holy Grail. Despite widespread use of secondary prevention medications, the risk of CVD was still high. It seems unlikely that 'more of same' will be the answer,” Gregory A. Nichols, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

The study, funded by GlaxoSmithKline, is the first to document CVD hospitalizations and all-cause mortality in patients with and without diabetes outside of a clinical trial, said Dr. Nichols of Kaiser Permanente NW, Portland, Ore.

The study population comprised 12,278 patients who were added to Kaiser's cardiovascular disease registry during 2000–2005 and followed through 2008 or until they died or left the health plan. Of the registry patients, 2,384 (19%) had diabetes and 9,894 (81%) did not. In both groups about 60% were male, and the mean age at baseline was 66 years.

The mean body mass index was significantly higher in the diabetic patients than in the nondiabetic patients (32.6 and 29.6 kg/m

Use of pharmacotherapy for CVD prevention was high in both groups, but the patients with diabetes were significantly more likely than were those without to be receiving antiplatelets (86% vs. 71%), ACE inhibitors and/or angiotensin receptor blockers (60% vs. 40%), beta-blockers (76% vs. 67%), and statins (71% vs. 64%).

Nonetheless, over a mean follow-up of nearly 4 years, 17% of the diabetes patients had a CVD hospitalization, compared with 10% of those without, a significant difference. Death occurred in 15% of the diabetes patients, compared with 13% of the nondiabetic patients, a nonsignificant difference. Cardiovascular disease hospitalizations occurred at an age- and sex-adjusted rate of 41 per 1,000 person-years in the diabetes group, compared with 25/1,000 in those without diabetes, Dr. Nichols reported.

The composite outcome—CVD hospitalizations and death—was greater in the diabetic group (32% vs. 23%), primarily owing to the difference in hospitalizations, he said.

Significant predictors of the composite outcome included age 65 or greater (hazard ratio 1.79), chronic kidney disease (HR 1.75), depression (1.35), and statin use (0.86). After full adjustment for those factors as well other demographic and clinical factors and medication use, the patients with diabetes were 40% more likely to be hospitalized for CVD, 34% more likely to die of all causes, and 42% more likely to experience the composite outcome.

One limitation of this study is that diabetes status was assessed only at baseline. “Undoubtedly, some portion of nondiabetic patients developed it during follow-up. Their events would be misclassified, thus making our estimates of the relative risk attributable to diabetes conservative,” noted Dr. Nichols, who disclosed that he has received research funding from GlaxoSmithKline, Merck & Co., Novartis Pharmaceuticals, and Novo Nordisk.

Over 4 years, 17% of the diabetes patients had a CVD hospitalization, versus 10% of those without. DR. NICHOLS

NEW ORLEANS — Among patients with established cardiovascular disease, diabetes increased the risk for secondary cardiovascular hospitalization or death by 42% in a prospective analysis of data from more than 12,000 members of Kaiser Permanente Northwest.

That increased risk was seen after adjustment for a wide range of risk factors associated with cardiovascular events, and in the setting of relatively high use of guideline-recommended medications for secondary prevention.

“Cardiovascular disease prevention in patients with diabetes remains the Holy Grail. Despite widespread use of secondary prevention medications, the risk of CVD was still high. It seems unlikely that 'more of same' will be the answer,” Gregory A. Nichols, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

The study, funded by GlaxoSmithKline, is the first to document CVD hospitalizations and all-cause mortality in patients with and without diabetes outside of a clinical trial, said Dr. Nichols of Kaiser Permanente NW, Portland, Ore.

The study population comprised 12,278 patients who were added to Kaiser's cardiovascular disease registry during 2000–2005 and followed through 2008 or until they died or left the health plan. Of the registry patients, 2,384 (19%) had diabetes and 9,894 (81%) did not. In both groups about 60% were male, and the mean age at baseline was 66 years.

The mean body mass index was significantly higher in the diabetic patients than in the nondiabetic patients (32.6 and 29.6 kg/m

Use of pharmacotherapy for CVD prevention was high in both groups, but the patients with diabetes were significantly more likely than were those without to be receiving antiplatelets (86% vs. 71%), ACE inhibitors and/or angiotensin receptor blockers (60% vs. 40%), beta-blockers (76% vs. 67%), and statins (71% vs. 64%).

Nonetheless, over a mean follow-up of nearly 4 years, 17% of the diabetes patients had a CVD hospitalization, compared with 10% of those without, a significant difference. Death occurred in 15% of the diabetes patients, compared with 13% of the nondiabetic patients, a nonsignificant difference. Cardiovascular disease hospitalizations occurred at an age- and sex-adjusted rate of 41 per 1,000 person-years in the diabetes group, compared with 25/1,000 in those without diabetes, Dr. Nichols reported.

The composite outcome—CVD hospitalizations and death—was greater in the diabetic group (32% vs. 23%), primarily owing to the difference in hospitalizations, he said.

Significant predictors of the composite outcome included age 65 or greater (hazard ratio 1.79), chronic kidney disease (HR 1.75), depression (1.35), and statin use (0.86). After full adjustment for those factors as well other demographic and clinical factors and medication use, the patients with diabetes were 40% more likely to be hospitalized for CVD, 34% more likely to die of all causes, and 42% more likely to experience the composite outcome.

One limitation of this study is that diabetes status was assessed only at baseline. “Undoubtedly, some portion of nondiabetic patients developed it during follow-up. Their events would be misclassified, thus making our estimates of the relative risk attributable to diabetes conservative,” noted Dr. Nichols, who disclosed that he has received research funding from GlaxoSmithKline, Merck & Co., Novartis Pharmaceuticals, and Novo Nordisk.

Over 4 years, 17% of the diabetes patients had a CVD hospitalization, versus 10% of those without. DR. NICHOLS

NEW ORLEANS — Among patients with established cardiovascular disease, diabetes increased the risk for secondary cardiovascular hospitalization or death by 42% in a prospective analysis of data from more than 12,000 members of Kaiser Permanente Northwest.

That increased risk was seen after adjustment for a wide range of risk factors associated with cardiovascular events, and in the setting of relatively high use of guideline-recommended medications for secondary prevention.

“Cardiovascular disease prevention in patients with diabetes remains the Holy Grail. Despite widespread use of secondary prevention medications, the risk of CVD was still high. It seems unlikely that 'more of same' will be the answer,” Gregory A. Nichols, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

The study, funded by GlaxoSmithKline, is the first to document CVD hospitalizations and all-cause mortality in patients with and without diabetes outside of a clinical trial, said Dr. Nichols of Kaiser Permanente NW, Portland, Ore.

The study population comprised 12,278 patients who were added to Kaiser's cardiovascular disease registry during 2000–2005 and followed through 2008 or until they died or left the health plan. Of the registry patients, 2,384 (19%) had diabetes and 9,894 (81%) did not. In both groups about 60% were male, and the mean age at baseline was 66 years.

The mean body mass index was significantly higher in the diabetic patients than in the nondiabetic patients (32.6 and 29.6 kg/m

Use of pharmacotherapy for CVD prevention was high in both groups, but the patients with diabetes were significantly more likely than were those without to be receiving antiplatelets (86% vs. 71%), ACE inhibitors and/or angiotensin receptor blockers (60% vs. 40%), beta-blockers (76% vs. 67%), and statins (71% vs. 64%).

Nonetheless, over a mean follow-up of nearly 4 years, 17% of the diabetes patients had a CVD hospitalization, compared with 10% of those without, a significant difference. Death occurred in 15% of the diabetes patients, compared with 13% of the nondiabetic patients, a nonsignificant difference. Cardiovascular disease hospitalizations occurred at an age- and sex-adjusted rate of 41 per 1,000 person-years in the diabetes group, compared with 25/1,000 in those without diabetes, Dr. Nichols reported.

The composite outcome—CVD hospitalizations and death—was greater in the diabetic group (32% vs. 23%), primarily owing to the difference in hospitalizations, he said.

Significant predictors of the composite outcome included age 65 or greater (hazard ratio 1.79), chronic kidney disease (HR 1.75), depression (1.35), and statin use (0.86). After full adjustment for those factors as well other demographic and clinical factors and medication use, the patients with diabetes were 40% more likely to be hospitalized for CVD, 34% more likely to die of all causes, and 42% more likely to experience the composite outcome.

One limitation of this study is that diabetes status was assessed only at baseline. “Undoubtedly, some portion of nondiabetic patients developed it during follow-up. Their events would be misclassified, thus making our estimates of the relative risk attributable to diabetes conservative,” noted Dr. Nichols, who disclosed that he has received research funding from GlaxoSmithKline, Merck & Co., Novartis Pharmaceuticals, and Novo Nordisk.

Over 4 years, 17% of the diabetes patients had a CVD hospitalization, versus 10% of those without. DR. NICHOLS

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel voted to drop the recommended number of postexposure doses of rabies vaccine from five to four, based on data suggesting that doing so would not adversely affect outcomes for exposed individuals.

The decision of the Advisory Committee on Immunization Practices stems from the “tenuous” nature of the rabies vaccine supply since 2007. The rabies vaccine made by Novartis (RabAvert) is now available for both pre-exposure and postexposure immunization without limitations. Sanofi Pasteur's rabies vaccine (Imovax) is still available only for postexposure prophylaxis, the CDC's Charles Rupprecht, V.M.D., said at ACIP's June meeting.

An interim four-dose schedule was developed to address the supply problem, and now the committee has advised the four-dose schedule for routine use, based on data from both animal and human clinical trials suggesting that recipients develop detectable rabies virus neutralizing antibodies by day 14, when a vaccine schedule of doses given at days 0, 3, 7, and 14 is used. (The fifth dose is given at 28 days.)

In addition, no significant differences were documented between the four- and five-dose rabies vaccine schedule in the relative amount of neutralizing antibodies produced. Equivalent outcomes were observed in comparison studies using four doses of vaccine given along with rabies immune globulin, said Dr. Rupprecht, chief of the CDC's rabies program.

Nonetheless, if ACIP's vote is approved by the CDC, it presents a conflict with the labeling approved by the Food and Drug Administration, which still recommends five doses of rabies vaccine. Any change to the labeling would require a request from the manufacturers and submission by them of additional data to support the change, FDA representative Dr. Norman Baylor said, adding that only in the event of a safety concern would the FDA be able to force such a change.

Spokesmen for Novartis and Sanofi Pasteur do not support the change. “It's what the committee feels is best based on the data available to them, but we can't talk about off-label use, and our label firmly states it's a five-dose regimen,” Sanofi Pasteur's Philip Hosbach said in an interview at the meeting.

Mr. Hosbach, vice president of immunization policy and government relations at Sanofi Pasteur, added that his company's supply issue stemmed from a planned shutdown of its manufacturing plant in 2007 for an upgrade. It is set to resume operation in the fourth quarter of 2009 with a full supply.

Clement Lewin, Ph.D., head of strategic immunization planning at Novartis Vaccines and Diagnostics, also reacted negatively to the ACIP vote. “It does mean a challenge for Novartis because the FDA guidance clearly states five doses and Novartis doesn't support off-label use of any of its products.”

He added, “We're currently supplying [rabies vaccine] for both pre- and postexposure prophylaxis. … Anyone who needs vaccine pre- or postexposure is able to get it. Last year the supply constraints were such that use was restricted to postexposure. Currently we are meeting all the demand of the United States. There is no supply issue at the moment,” Dr. Lewin said in an on-site interview.

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel voted to drop the recommended number of postexposure doses of rabies vaccine from five to four, based on data suggesting that doing so would not adversely affect outcomes for exposed individuals.

The decision of the Advisory Committee on Immunization Practices stems from the “tenuous” nature of the rabies vaccine supply since 2007. The rabies vaccine made by Novartis (RabAvert) is now available for both pre-exposure and postexposure immunization without limitations. Sanofi Pasteur's rabies vaccine (Imovax) is still available only for postexposure prophylaxis, the CDC's Charles Rupprecht, V.M.D., said at ACIP's June meeting.

An interim four-dose schedule was developed to address the supply problem, and now the committee has advised the four-dose schedule for routine use, based on data from both animal and human clinical trials suggesting that recipients develop detectable rabies virus neutralizing antibodies by day 14, when a vaccine schedule of doses given at days 0, 3, 7, and 14 is used. (The fifth dose is given at 28 days.)

In addition, no significant differences were documented between the four- and five-dose rabies vaccine schedule in the relative amount of neutralizing antibodies produced. Equivalent outcomes were observed in comparison studies using four doses of vaccine given along with rabies immune globulin, said Dr. Rupprecht, chief of the CDC's rabies program.

Nonetheless, if ACIP's vote is approved by the CDC, it presents a conflict with the labeling approved by the Food and Drug Administration, which still recommends five doses of rabies vaccine. Any change to the labeling would require a request from the manufacturers and submission by them of additional data to support the change, FDA representative Dr. Norman Baylor said, adding that only in the event of a safety concern would the FDA be able to force such a change.

Spokesmen for Novartis and Sanofi Pasteur do not support the change. “It's what the committee feels is best based on the data available to them, but we can't talk about off-label use, and our label firmly states it's a five-dose regimen,” Sanofi Pasteur's Philip Hosbach said in an interview at the meeting.

Mr. Hosbach, vice president of immunization policy and government relations at Sanofi Pasteur, added that his company's supply issue stemmed from a planned shutdown of its manufacturing plant in 2007 for an upgrade. It is set to resume operation in the fourth quarter of 2009 with a full supply.

Clement Lewin, Ph.D., head of strategic immunization planning at Novartis Vaccines and Diagnostics, also reacted negatively to the ACIP vote. “It does mean a challenge for Novartis because the FDA guidance clearly states five doses and Novartis doesn't support off-label use of any of its products.”

He added, “We're currently supplying [rabies vaccine] for both pre- and postexposure prophylaxis. … Anyone who needs vaccine pre- or postexposure is able to get it. Last year the supply constraints were such that use was restricted to postexposure. Currently we are meeting all the demand of the United States. There is no supply issue at the moment,” Dr. Lewin said in an on-site interview.

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel voted to drop the recommended number of postexposure doses of rabies vaccine from five to four, based on data suggesting that doing so would not adversely affect outcomes for exposed individuals.

The decision of the Advisory Committee on Immunization Practices stems from the “tenuous” nature of the rabies vaccine supply since 2007. The rabies vaccine made by Novartis (RabAvert) is now available for both pre-exposure and postexposure immunization without limitations. Sanofi Pasteur's rabies vaccine (Imovax) is still available only for postexposure prophylaxis, the CDC's Charles Rupprecht, V.M.D., said at ACIP's June meeting.

An interim four-dose schedule was developed to address the supply problem, and now the committee has advised the four-dose schedule for routine use, based on data from both animal and human clinical trials suggesting that recipients develop detectable rabies virus neutralizing antibodies by day 14, when a vaccine schedule of doses given at days 0, 3, 7, and 14 is used. (The fifth dose is given at 28 days.)

In addition, no significant differences were documented between the four- and five-dose rabies vaccine schedule in the relative amount of neutralizing antibodies produced. Equivalent outcomes were observed in comparison studies using four doses of vaccine given along with rabies immune globulin, said Dr. Rupprecht, chief of the CDC's rabies program.

Nonetheless, if ACIP's vote is approved by the CDC, it presents a conflict with the labeling approved by the Food and Drug Administration, which still recommends five doses of rabies vaccine. Any change to the labeling would require a request from the manufacturers and submission by them of additional data to support the change, FDA representative Dr. Norman Baylor said, adding that only in the event of a safety concern would the FDA be able to force such a change.

Spokesmen for Novartis and Sanofi Pasteur do not support the change. “It's what the committee feels is best based on the data available to them, but we can't talk about off-label use, and our label firmly states it's a five-dose regimen,” Sanofi Pasteur's Philip Hosbach said in an interview at the meeting.

Mr. Hosbach, vice president of immunization policy and government relations at Sanofi Pasteur, added that his company's supply issue stemmed from a planned shutdown of its manufacturing plant in 2007 for an upgrade. It is set to resume operation in the fourth quarter of 2009 with a full supply.

Clement Lewin, Ph.D., head of strategic immunization planning at Novartis Vaccines and Diagnostics, also reacted negatively to the ACIP vote. “It does mean a challenge for Novartis because the FDA guidance clearly states five doses and Novartis doesn't support off-label use of any of its products.”

He added, “We're currently supplying [rabies vaccine] for both pre- and postexposure prophylaxis. … Anyone who needs vaccine pre- or postexposure is able to get it. Last year the supply constraints were such that use was restricted to postexposure. Currently we are meeting all the demand of the United States. There is no supply issue at the moment,” Dr. Lewin said in an on-site interview.

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel recommended the use of either the combination measles-mumps-rubella-varicella vaccine or the separate MMR and varicella vaccines for children at 12–15 months of age, but to retain a preference for the MMRV vaccine for the second dose given at 4–6 years of age.

The issue was addressed by the Advisory Committee on Immunization Practices (ACIP) at its June meeting because data had emerged last year suggesting an increased risk for febrile seizures in very young children given MMRV, compared with children given the MMR and varicella vaccines separately. ACIP had previously stated a general preference for the use of combination vaccines over separate vaccines whenever possible, said Dr. Jonathan Temte, MMRV vaccine safety working group chair.

In a separate vote, ACIP qualified the language for that preference—contained in its general vaccine recommendations—to say that although combination vaccines are still “generally” preferred over separate injections of equivalent components, “considerations should include provider assessment, patient preference, and potential for adverse events,” along with other factors.

“In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent. Public trust in the safety and efficacy of vaccines is key to the success of immunization programs,” said Dr. Temte of the department of family medicine at the University of Wisconsin, Madison.

The MMRV vaccine—Merck & Co.'s ProQuad—is not on the U.S. market but is expected in 2010, a company spokesman said.

The American Academy of Pediatrics Committee on Infectious Diseases (COID) will take ACIP's vote into consideration, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“The COID has not finished its deliberations on this. But, what this did was to remove the preference for MMRV. This now means the practitioner will have the opportunity, with the parents, to discuss the increased risk of febrile seizures associated with MMRV and make a provider/parent decision about whether to give two shots or one shot with a slightly increased risk.”

As to whether the COID—which Dr. Bocchini chairs—will come to the same conclusion, “I think it's possible they'll be in alignment, but I can't really say right now,” he said.

The vote on dose 2 was more straightforward, he noted. “The risk of febrile seizures in that age group is low…. So, under usual circumstances a combination vaccine would be preferred,” said Dr. Bocchini of Louisiana State University, Shreveport.

During the meeting, Dr. Karen Broder of the CDC's Immunization Safety Office presented a summary of evidence from two studies—one from the CDC's Vaccine Safety Datalink, the other from Merck—which together showed an approximately twofold elevated risk for febrile seizures among children aged 12–23 months in the 2 weeks following receipt of MMRV, compared with receipt of separate MMR and varicella vaccines. After vaccination, 7–9 febrile seizures occur per 10,000 children vaccinated with MMRV, compared with 3–4/10,000 with the separate vaccines.

After dose 1 of MMRV vaccine, 1 additional febrile seizure is expected to occur per approximately 2,300–2,600 children vaccinated, compared with when MMR and varicella vaccines are given separately, Dr. Broder said.

There was no increased risk for febrile seizure after dose 2, which is given to children at 4–6 years of age, although less information is available about the risk in that age group, she noted.

Committee members were divided on the dose 1 decision, with 4 of 14 members voting “no” to giving equal preference for the first dose, stating that they would rather see a preference for giving MMR and varicella vaccines separately. Among the concerns they raised were the need for storing all three vaccines, the need for scheduling additional visits, the extra time it would take to counsel parents about the risk of febrile seizures, and the fact that providers are paid two administration fees for giving the two separate shots.

But panel members who supported the vote for equal choice noted that although febrile seizures are scary to parents, most of these seizures are not of great medical consequence. A few panelists noted that expressing a preference for giving MMR and varicella separately would interfere with physician and patient choice, and might lead to decreased vaccine coverage because of the need for separate injections.

In other business, ACIP voted to apply these recommendations to children receiving the vaccines at ages other than those recommended, and to include the changes in the Vaccines for Children Program.

ACIP members who have conflicts of interest are required to abstain from voting.

Dr. Jonathan Temte said, “In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent.” ©Parker Smith Photography

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel recommended the use of either the combination measles-mumps-rubella-varicella vaccine or the separate MMR and varicella vaccines for children at 12–15 months of age, but to retain a preference for the MMRV vaccine for the second dose given at 4–6 years of age.

The issue was addressed by the Advisory Committee on Immunization Practices (ACIP) at its June meeting because data had emerged last year suggesting an increased risk for febrile seizures in very young children given MMRV, compared with children given the MMR and varicella vaccines separately. ACIP had previously stated a general preference for the use of combination vaccines over separate vaccines whenever possible, said Dr. Jonathan Temte, MMRV vaccine safety working group chair.

In a separate vote, ACIP qualified the language for that preference—contained in its general vaccine recommendations—to say that although combination vaccines are still “generally” preferred over separate injections of equivalent components, “considerations should include provider assessment, patient preference, and potential for adverse events,” along with other factors.

“In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent. Public trust in the safety and efficacy of vaccines is key to the success of immunization programs,” said Dr. Temte of the department of family medicine at the University of Wisconsin, Madison.

The MMRV vaccine—Merck & Co.'s ProQuad—is not on the U.S. market but is expected in 2010, a company spokesman said.

The American Academy of Pediatrics Committee on Infectious Diseases (COID) will take ACIP's vote into consideration, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“The COID has not finished its deliberations on this. But, what this did was to remove the preference for MMRV. This now means the practitioner will have the opportunity, with the parents, to discuss the increased risk of febrile seizures associated with MMRV and make a provider/parent decision about whether to give two shots or one shot with a slightly increased risk.”

As to whether the COID—which Dr. Bocchini chairs—will come to the same conclusion, “I think it's possible they'll be in alignment, but I can't really say right now,” he said.

The vote on dose 2 was more straightforward, he noted. “The risk of febrile seizures in that age group is low…. So, under usual circumstances a combination vaccine would be preferred,” said Dr. Bocchini of Louisiana State University, Shreveport.

During the meeting, Dr. Karen Broder of the CDC's Immunization Safety Office presented a summary of evidence from two studies—one from the CDC's Vaccine Safety Datalink, the other from Merck—which together showed an approximately twofold elevated risk for febrile seizures among children aged 12–23 months in the 2 weeks following receipt of MMRV, compared with receipt of separate MMR and varicella vaccines. After vaccination, 7–9 febrile seizures occur per 10,000 children vaccinated with MMRV, compared with 3–4/10,000 with the separate vaccines.

After dose 1 of MMRV vaccine, 1 additional febrile seizure is expected to occur per approximately 2,300–2,600 children vaccinated, compared with when MMR and varicella vaccines are given separately, Dr. Broder said.

There was no increased risk for febrile seizure after dose 2, which is given to children at 4–6 years of age, although less information is available about the risk in that age group, she noted.

Committee members were divided on the dose 1 decision, with 4 of 14 members voting “no” to giving equal preference for the first dose, stating that they would rather see a preference for giving MMR and varicella vaccines separately. Among the concerns they raised were the need for storing all three vaccines, the need for scheduling additional visits, the extra time it would take to counsel parents about the risk of febrile seizures, and the fact that providers are paid two administration fees for giving the two separate shots.

But panel members who supported the vote for equal choice noted that although febrile seizures are scary to parents, most of these seizures are not of great medical consequence. A few panelists noted that expressing a preference for giving MMR and varicella separately would interfere with physician and patient choice, and might lead to decreased vaccine coverage because of the need for separate injections.

In other business, ACIP voted to apply these recommendations to children receiving the vaccines at ages other than those recommended, and to include the changes in the Vaccines for Children Program.

ACIP members who have conflicts of interest are required to abstain from voting.

Dr. Jonathan Temte said, “In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent.” ©Parker Smith Photography

ATLANTA — The Centers for Disease Control and Prevention's vaccine advisory panel recommended the use of either the combination measles-mumps-rubella-varicella vaccine or the separate MMR and varicella vaccines for children at 12–15 months of age, but to retain a preference for the MMRV vaccine for the second dose given at 4–6 years of age.

The issue was addressed by the Advisory Committee on Immunization Practices (ACIP) at its June meeting because data had emerged last year suggesting an increased risk for febrile seizures in very young children given MMRV, compared with children given the MMR and varicella vaccines separately. ACIP had previously stated a general preference for the use of combination vaccines over separate vaccines whenever possible, said Dr. Jonathan Temte, MMRV vaccine safety working group chair.

In a separate vote, ACIP qualified the language for that preference—contained in its general vaccine recommendations—to say that although combination vaccines are still “generally” preferred over separate injections of equivalent components, “considerations should include provider assessment, patient preference, and potential for adverse events,” along with other factors.

“In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent. Public trust in the safety and efficacy of vaccines is key to the success of immunization programs,” said Dr. Temte of the department of family medicine at the University of Wisconsin, Madison.

The MMRV vaccine—Merck & Co.'s ProQuad—is not on the U.S. market but is expected in 2010, a company spokesman said.

The American Academy of Pediatrics Committee on Infectious Diseases (COID) will take ACIP's vote into consideration, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“The COID has not finished its deliberations on this. But, what this did was to remove the preference for MMRV. This now means the practitioner will have the opportunity, with the parents, to discuss the increased risk of febrile seizures associated with MMRV and make a provider/parent decision about whether to give two shots or one shot with a slightly increased risk.”

As to whether the COID—which Dr. Bocchini chairs—will come to the same conclusion, “I think it's possible they'll be in alignment, but I can't really say right now,” he said.

The vote on dose 2 was more straightforward, he noted. “The risk of febrile seizures in that age group is low…. So, under usual circumstances a combination vaccine would be preferred,” said Dr. Bocchini of Louisiana State University, Shreveport.

During the meeting, Dr. Karen Broder of the CDC's Immunization Safety Office presented a summary of evidence from two studies—one from the CDC's Vaccine Safety Datalink, the other from Merck—which together showed an approximately twofold elevated risk for febrile seizures among children aged 12–23 months in the 2 weeks following receipt of MMRV, compared with receipt of separate MMR and varicella vaccines. After vaccination, 7–9 febrile seizures occur per 10,000 children vaccinated with MMRV, compared with 3–4/10,000 with the separate vaccines.

After dose 1 of MMRV vaccine, 1 additional febrile seizure is expected to occur per approximately 2,300–2,600 children vaccinated, compared with when MMR and varicella vaccines are given separately, Dr. Broder said.

There was no increased risk for febrile seizure after dose 2, which is given to children at 4–6 years of age, although less information is available about the risk in that age group, she noted.

Committee members were divided on the dose 1 decision, with 4 of 14 members voting “no” to giving equal preference for the first dose, stating that they would rather see a preference for giving MMR and varicella vaccines separately. Among the concerns they raised were the need for storing all three vaccines, the need for scheduling additional visits, the extra time it would take to counsel parents about the risk of febrile seizures, and the fact that providers are paid two administration fees for giving the two separate shots.

But panel members who supported the vote for equal choice noted that although febrile seizures are scary to parents, most of these seizures are not of great medical consequence. A few panelists noted that expressing a preference for giving MMR and varicella separately would interfere with physician and patient choice, and might lead to decreased vaccine coverage because of the need for separate injections.

In other business, ACIP voted to apply these recommendations to children receiving the vaccines at ages other than those recommended, and to include the changes in the Vaccines for Children Program.

ACIP members who have conflicts of interest are required to abstain from voting.

Dr. Jonathan Temte said, “In the era of the lowest levels of vaccine-preventable diseases, increasingly parents express more fear of vaccines than of diseases they prevent.” ©Parker Smith Photography

NEW ORLEANS — Findings from the RECORD study confirm the growing consensus that rosiglitazone should not be used in patients with a history of heart failure, with previous problems that might have led to myocardial damage, or in women who are at increased risk for fractures.

However, “Although our evidence is insufficient to rule out a small increased risk of myocardial infarction caused by rosiglitazone when compared with other glucose-lowering agents, it appears that for people with type 2 diabetes, rosiglitazone can be used without concern that there is increased overall cardiovascular morbidity and mortality, or for that matter, all-cause mortality,” study chair Philip D. Home said at the annual scientific sessions of the American Diabetes Association.

“We recommend monitoring for fluid retention,” added Dr. Home, professor of diabetes medicine at Newcastle University, England.

In the prospective, multicenter, open-label Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes (RECORD) trial, funded by GlaxoSmithKline, addition of rosiglitazone (Avandia) to either sulfonylurea or metformin therapy in people with type 2 diabetes increased their risk for heart failure but did not increase the risk of overall cardiovascular morbidity or mortality in a mean follow-up of 5.5 years (Lancet 2009 June 5 [doi:10.1016/S0140-6736(09)60953-3]).

The study was originally designed to evaluate noninferiority of rosiglitazone on cardiovascular outcomes and glucose control, compared with sulfonyl-urea, over a 6-year period. It included a total of 4,447 patients with type 2 diabetes whose glucose levels were inadequately controlled with either sulfonylurea or metformin alone.

Patients in the trial—seen in 364 centers in 25 countries in Europe and Australasia—were aged 40-75 years, had a body mass index greater than 25 kg/m2, and had hemoglobin A1c levels between 7.0% and 9.0% (mean 7.9%) despite maximal doses of either sulfonyl-urea or metformin monotherapy. Patients who were taking sulfonylurea initially were randomized to add-on treatment of either rosiglitazone or metformin (as “active comparator”) while those already on metformin were randomized to the addition of either rosiglitazone or sulfonylurea.

Rosiglitazone was added at a starting doses of 4 mg/day and titrated up as needed to achieve a target HbA1c of 7.0% or less. Any patient who had an HbA1c of 8.5% or more with the two agents was “rescued” with either a third oral agent (if taking rosiglitazone) or transferred to insulin if on metformin/sulfonylurea. A total of 2,220 were randomized to receive rosiglitazone, and 2,227 to the active control group (sulfonyl-urea plus metformin).

The overall rate of the primary end point, cardiovascular hospitalization or cardiovascular death, was 28 per 1,000 person-years, occurring in 321 rosiglitazone patients and 323 active control patients. The hazard ratio of 0.99 met the prespecified noninferiority criteria. Excluding cardiovascular events not of atherosclerotic origin gave similar results (HR 0.97).

The predefined composite secondary end point of cardiovascular death, myocardial infarction, and stroke gave a hazard ratio of 0.93 for rosiglitazone vs. active comparator, suggesting a slight but not statistically significant benefit for rosiglitazone. Cardiovascular death and all-cause death were also slightly in favor of rosiglitazone but not statistically significant (HR 0.84 and 0.86, respectively). The hazard ratio for MI was 1.14—there were eight excess cases with rosiglitazone—but this was also statistically nonsignificant.

Heart failure was highly significantly increased with rosiglitazone, with a hazard ratio of 2.10. Increased heart failure with rosiglitazone has been reported previously in other studies, and in an earlier interim analysis of RECORD (N. Engl. J. Med. 2007;357:28-38).

The overall incidence of participant-reported bone fractures was higher in the rosiglitazone group than in the active control group, with a risk ratio of 1.57, higher for women than men (1.82 vs. 1.23). Fractures of the upper limb and distal lower limb were increased, but hip and femur fractures were not.

In the final results, the statistical power for RECORD was less than initially planned because the overall primary event rate in the 4,447 patients followed for a mean of 5.5 years was substantially lower than anticipated. Reasons for this aren't entirely clear, but an editorial that accompanied the interim analysis of the study suggested that incomplete analysis due to a high loss to follow-up (10%) and the differences in medical care in the various countries where the trial was conducted were possible factors.

Dr. Home disclosed that he is on an advisory panel and speakers bureau for, and receives research support from, GlaxoSmithKline. He also has financial relationships with a variety of other companies that make diabetes-related products.

Hazard ratios for rosiglitazone patients were 2.10 for heart failure and 1.57 for bone fractures. DR. HOME

NEW ORLEANS — Findings from the RECORD study confirm the growing consensus that rosiglitazone should not be used in patients with a history of heart failure, with previous problems that might have led to myocardial damage, or in women who are at increased risk for fractures.

However, “Although our evidence is insufficient to rule out a small increased risk of myocardial infarction caused by rosiglitazone when compared with other glucose-lowering agents, it appears that for people with type 2 diabetes, rosiglitazone can be used without concern that there is increased overall cardiovascular morbidity and mortality, or for that matter, all-cause mortality,” study chair Philip D. Home said at the annual scientific sessions of the American Diabetes Association.

“We recommend monitoring for fluid retention,” added Dr. Home, professor of diabetes medicine at Newcastle University, England.

In the prospective, multicenter, open-label Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes (RECORD) trial, funded by GlaxoSmithKline, addition of rosiglitazone (Avandia) to either sulfonylurea or metformin therapy in people with type 2 diabetes increased their risk for heart failure but did not increase the risk of overall cardiovascular morbidity or mortality in a mean follow-up of 5.5 years (Lancet 2009 June 5 [doi:10.1016/S0140-6736(09)60953-3]).

The study was originally designed to evaluate noninferiority of rosiglitazone on cardiovascular outcomes and glucose control, compared with sulfonyl-urea, over a 6-year period. It included a total of 4,447 patients with type 2 diabetes whose glucose levels were inadequately controlled with either sulfonylurea or metformin alone.

Patients in the trial—seen in 364 centers in 25 countries in Europe and Australasia—were aged 40-75 years, had a body mass index greater than 25 kg/m2, and had hemoglobin A1c levels between 7.0% and 9.0% (mean 7.9%) despite maximal doses of either sulfonyl-urea or metformin monotherapy. Patients who were taking sulfonylurea initially were randomized to add-on treatment of either rosiglitazone or metformin (as “active comparator”) while those already on metformin were randomized to the addition of either rosiglitazone or sulfonylurea.

Rosiglitazone was added at a starting doses of 4 mg/day and titrated up as needed to achieve a target HbA1c of 7.0% or less. Any patient who had an HbA1c of 8.5% or more with the two agents was “rescued” with either a third oral agent (if taking rosiglitazone) or transferred to insulin if on metformin/sulfonylurea. A total of 2,220 were randomized to receive rosiglitazone, and 2,227 to the active control group (sulfonyl-urea plus metformin).

The overall rate of the primary end point, cardiovascular hospitalization or cardiovascular death, was 28 per 1,000 person-years, occurring in 321 rosiglitazone patients and 323 active control patients. The hazard ratio of 0.99 met the prespecified noninferiority criteria. Excluding cardiovascular events not of atherosclerotic origin gave similar results (HR 0.97).

The predefined composite secondary end point of cardiovascular death, myocardial infarction, and stroke gave a hazard ratio of 0.93 for rosiglitazone vs. active comparator, suggesting a slight but not statistically significant benefit for rosiglitazone. Cardiovascular death and all-cause death were also slightly in favor of rosiglitazone but not statistically significant (HR 0.84 and 0.86, respectively). The hazard ratio for MI was 1.14—there were eight excess cases with rosiglitazone—but this was also statistically nonsignificant.

Heart failure was highly significantly increased with rosiglitazone, with a hazard ratio of 2.10. Increased heart failure with rosiglitazone has been reported previously in other studies, and in an earlier interim analysis of RECORD (N. Engl. J. Med. 2007;357:28-38).

The overall incidence of participant-reported bone fractures was higher in the rosiglitazone group than in the active control group, with a risk ratio of 1.57, higher for women than men (1.82 vs. 1.23). Fractures of the upper limb and distal lower limb were increased, but hip and femur fractures were not.

In the final results, the statistical power for RECORD was less than initially planned because the overall primary event rate in the 4,447 patients followed for a mean of 5.5 years was substantially lower than anticipated. Reasons for this aren't entirely clear, but an editorial that accompanied the interim analysis of the study suggested that incomplete analysis due to a high loss to follow-up (10%) and the differences in medical care in the various countries where the trial was conducted were possible factors.

Dr. Home disclosed that he is on an advisory panel and speakers bureau for, and receives research support from, GlaxoSmithKline. He also has financial relationships with a variety of other companies that make diabetes-related products.

Hazard ratios for rosiglitazone patients were 2.10 for heart failure and 1.57 for bone fractures. DR. HOME

NEW ORLEANS — Findings from the RECORD study confirm the growing consensus that rosiglitazone should not be used in patients with a history of heart failure, with previous problems that might have led to myocardial damage, or in women who are at increased risk for fractures.

However, “Although our evidence is insufficient to rule out a small increased risk of myocardial infarction caused by rosiglitazone when compared with other glucose-lowering agents, it appears that for people with type 2 diabetes, rosiglitazone can be used without concern that there is increased overall cardiovascular morbidity and mortality, or for that matter, all-cause mortality,” study chair Philip D. Home said at the annual scientific sessions of the American Diabetes Association.

“We recommend monitoring for fluid retention,” added Dr. Home, professor of diabetes medicine at Newcastle University, England.

In the prospective, multicenter, open-label Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes (RECORD) trial, funded by GlaxoSmithKline, addition of rosiglitazone (Avandia) to either sulfonylurea or metformin therapy in people with type 2 diabetes increased their risk for heart failure but did not increase the risk of overall cardiovascular morbidity or mortality in a mean follow-up of 5.5 years (Lancet 2009 June 5 [doi:10.1016/S0140-6736(09)60953-3]).

The study was originally designed to evaluate noninferiority of rosiglitazone on cardiovascular outcomes and glucose control, compared with sulfonyl-urea, over a 6-year period. It included a total of 4,447 patients with type 2 diabetes whose glucose levels were inadequately controlled with either sulfonylurea or metformin alone.

Patients in the trial—seen in 364 centers in 25 countries in Europe and Australasia—were aged 40-75 years, had a body mass index greater than 25 kg/m2, and had hemoglobin A1c levels between 7.0% and 9.0% (mean 7.9%) despite maximal doses of either sulfonyl-urea or metformin monotherapy. Patients who were taking sulfonylurea initially were randomized to add-on treatment of either rosiglitazone or metformin (as “active comparator”) while those already on metformin were randomized to the addition of either rosiglitazone or sulfonylurea.

Rosiglitazone was added at a starting doses of 4 mg/day and titrated up as needed to achieve a target HbA1c of 7.0% or less. Any patient who had an HbA1c of 8.5% or more with the two agents was “rescued” with either a third oral agent (if taking rosiglitazone) or transferred to insulin if on metformin/sulfonylurea. A total of 2,220 were randomized to receive rosiglitazone, and 2,227 to the active control group (sulfonyl-urea plus metformin).

The overall rate of the primary end point, cardiovascular hospitalization or cardiovascular death, was 28 per 1,000 person-years, occurring in 321 rosiglitazone patients and 323 active control patients. The hazard ratio of 0.99 met the prespecified noninferiority criteria. Excluding cardiovascular events not of atherosclerotic origin gave similar results (HR 0.97).

The predefined composite secondary end point of cardiovascular death, myocardial infarction, and stroke gave a hazard ratio of 0.93 for rosiglitazone vs. active comparator, suggesting a slight but not statistically significant benefit for rosiglitazone. Cardiovascular death and all-cause death were also slightly in favor of rosiglitazone but not statistically significant (HR 0.84 and 0.86, respectively). The hazard ratio for MI was 1.14—there were eight excess cases with rosiglitazone—but this was also statistically nonsignificant.

Heart failure was highly significantly increased with rosiglitazone, with a hazard ratio of 2.10. Increased heart failure with rosiglitazone has been reported previously in other studies, and in an earlier interim analysis of RECORD (N. Engl. J. Med. 2007;357:28-38).

The overall incidence of participant-reported bone fractures was higher in the rosiglitazone group than in the active control group, with a risk ratio of 1.57, higher for women than men (1.82 vs. 1.23). Fractures of the upper limb and distal lower limb were increased, but hip and femur fractures were not.

In the final results, the statistical power for RECORD was less than initially planned because the overall primary event rate in the 4,447 patients followed for a mean of 5.5 years was substantially lower than anticipated. Reasons for this aren't entirely clear, but an editorial that accompanied the interim analysis of the study suggested that incomplete analysis due to a high loss to follow-up (10%) and the differences in medical care in the various countries where the trial was conducted were possible factors.

Dr. Home disclosed that he is on an advisory panel and speakers bureau for, and receives research support from, GlaxoSmithKline. He also has financial relationships with a variety of other companies that make diabetes-related products.

Hazard ratios for rosiglitazone patients were 2.10 for heart failure and 1.57 for bone fractures. DR. HOME

NEW ORLEANS — The proportion of gestational diabetes cases attributable to overweight and obesity totaled 46% in a population-based study of more than 20,000 women from seven U.S. states.

The data, from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS), were used to generate a population-based estimate of the contribution of prepregnancy overweight and obesity to the development of gestational diabetes mellitus (GDM). Shin Y. Kim reported the results at the annual scientific sessions of the American Diabetes Association.

“If we assume that the relationship between GDM and obesity and overweight is causal and no other confounders exist, then a large proportion of GDM cases are potentially preventable,” said Dr. Kim of the CDC's division of reproductive health.

She and her associates analyzed PRAMS data from the seven states that had implemented the 2003 revised birth certificate, which distinguishes GDM from diabetes that existed prior to pregnancy. The surveillance system collects data via a questionnaire from mothers of newborns 2-6 months after delivery. A total of 22,767 women with complete chart information who did not have pre-existing diabetes were included.

The overall GDM prevalence was 4%, ranging from 3.1% in Florida to 5% in Ohio. (The other five states were Nebraska, South Carolina, Utah, Washington, and New York, excluding New York City.) More than 70% of the women with GDM had a prepregnancy body mass index of at least 25 kg/m2, compared with 44.9% of the women who did not have GDM during pregnancy, Ms. Kim reported.

The GDM prevalence was 0.7% for women classified as underweight (body mass index 13-18.4 kg/m2) prior to pregnancy, 2.3% for those with normal weight (BMI 18.5-24.9), 4.8% for overweight women (25-29.9), 5.5% for those who were obese (30-34.9), and 11.5% for extremely obese women (35-64.9). With normal weight used as the reference group, the unadjusted relative risks of developing GDM were 2.1, 2.4, and 5 for women who were overweight, obese, and extremely obese, respectively.

“The probability of GDM increases with increasing BMI, with no clear BMI threshold below which a dose-response relationship was not evident,” Ms. Kim said.

The relative risks did not change after adjustment for maternal age, race/ethnicity, marital status, or parity. Once adjusted, the proportions of gestational diabetes cases attributable to overweight, obesity, and extreme obesity were 15.4%, 9.7%, and 21.1%, for a total of 46.2%. “In other words, if all women with a BMI of 25 or greater had a GDM risk equal to that of women in the normal BMI category, nearly half of GDM cases could be prevented. Lifestyle interventions to reduce BMI have the potential to lower GDM risk,” she commented.

There are a few possible reasons for why overweight/obesity contributed to only about half of GDM cases, Ms. Kim said in a follow-up interview.

“First, prepregnancy weight was self-reported, and women tend to underreport their weight. This may have led us to underestimate the contribution of overweight and obesity to the fraction of GDM attributable to weight. Also, there may be a race/ethnic difference in the relationship between BMI and GDM risk, and our analysis overrepresents non-Hispanic white women compared to the general population,” she noted.

If the analyses had been done using data representing the entire U.S. population, she continued, the study might have generated a larger estimate of the proportion of GDM cases associated with a high BMI. “Physical activity also contributes to GDM risk, and we had no data on physical activity levels in our study population. In addition, BMI is not a perfect measure of body fat, but we use it often because it can easily be obtained. If we had used lean women as our reference group, the [attributable proportion] would have been much higher. This is because the GDM risk increased in a nearly linear fashion as BMI increased.”

However, she said, the 46% estimate from this study is “higher than other non-population-based estimates found in the literature, and the dose-response relationship is consistent with estimates found in the general population with type 2 diabetes.”

Ms. Kim stated that she had no disclosures to make.

NEW ORLEANS — The proportion of gestational diabetes cases attributable to overweight and obesity totaled 46% in a population-based study of more than 20,000 women from seven U.S. states.

The data, from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS), were used to generate a population-based estimate of the contribution of prepregnancy overweight and obesity to the development of gestational diabetes mellitus (GDM). Shin Y. Kim reported the results at the annual scientific sessions of the American Diabetes Association.

“If we assume that the relationship between GDM and obesity and overweight is causal and no other confounders exist, then a large proportion of GDM cases are potentially preventable,” said Dr. Kim of the CDC's division of reproductive health.

She and her associates analyzed PRAMS data from the seven states that had implemented the 2003 revised birth certificate, which distinguishes GDM from diabetes that existed prior to pregnancy. The surveillance system collects data via a questionnaire from mothers of newborns 2-6 months after delivery. A total of 22,767 women with complete chart information who did not have pre-existing diabetes were included.

The overall GDM prevalence was 4%, ranging from 3.1% in Florida to 5% in Ohio. (The other five states were Nebraska, South Carolina, Utah, Washington, and New York, excluding New York City.) More than 70% of the women with GDM had a prepregnancy body mass index of at least 25 kg/m2, compared with 44.9% of the women who did not have GDM during pregnancy, Ms. Kim reported.

The GDM prevalence was 0.7% for women classified as underweight (body mass index 13-18.4 kg/m2) prior to pregnancy, 2.3% for those with normal weight (BMI 18.5-24.9), 4.8% for overweight women (25-29.9), 5.5% for those who were obese (30-34.9), and 11.5% for extremely obese women (35-64.9). With normal weight used as the reference group, the unadjusted relative risks of developing GDM were 2.1, 2.4, and 5 for women who were overweight, obese, and extremely obese, respectively.

“The probability of GDM increases with increasing BMI, with no clear BMI threshold below which a dose-response relationship was not evident,” Ms. Kim said.

The relative risks did not change after adjustment for maternal age, race/ethnicity, marital status, or parity. Once adjusted, the proportions of gestational diabetes cases attributable to overweight, obesity, and extreme obesity were 15.4%, 9.7%, and 21.1%, for a total of 46.2%. “In other words, if all women with a BMI of 25 or greater had a GDM risk equal to that of women in the normal BMI category, nearly half of GDM cases could be prevented. Lifestyle interventions to reduce BMI have the potential to lower GDM risk,” she commented.

There are a few possible reasons for why overweight/obesity contributed to only about half of GDM cases, Ms. Kim said in a follow-up interview.

“First, prepregnancy weight was self-reported, and women tend to underreport their weight. This may have led us to underestimate the contribution of overweight and obesity to the fraction of GDM attributable to weight. Also, there may be a race/ethnic difference in the relationship between BMI and GDM risk, and our analysis overrepresents non-Hispanic white women compared to the general population,” she noted.

If the analyses had been done using data representing the entire U.S. population, she continued, the study might have generated a larger estimate of the proportion of GDM cases associated with a high BMI. “Physical activity also contributes to GDM risk, and we had no data on physical activity levels in our study population. In addition, BMI is not a perfect measure of body fat, but we use it often because it can easily be obtained. If we had used lean women as our reference group, the [attributable proportion] would have been much higher. This is because the GDM risk increased in a nearly linear fashion as BMI increased.”

However, she said, the 46% estimate from this study is “higher than other non-population-based estimates found in the literature, and the dose-response relationship is consistent with estimates found in the general population with type 2 diabetes.”

Ms. Kim stated that she had no disclosures to make.

NEW ORLEANS — The proportion of gestational diabetes cases attributable to overweight and obesity totaled 46% in a population-based study of more than 20,000 women from seven U.S. states.

The data, from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS), were used to generate a population-based estimate of the contribution of prepregnancy overweight and obesity to the development of gestational diabetes mellitus (GDM). Shin Y. Kim reported the results at the annual scientific sessions of the American Diabetes Association.

“If we assume that the relationship between GDM and obesity and overweight is causal and no other confounders exist, then a large proportion of GDM cases are potentially preventable,” said Dr. Kim of the CDC's division of reproductive health.

She and her associates analyzed PRAMS data from the seven states that had implemented the 2003 revised birth certificate, which distinguishes GDM from diabetes that existed prior to pregnancy. The surveillance system collects data via a questionnaire from mothers of newborns 2-6 months after delivery. A total of 22,767 women with complete chart information who did not have pre-existing diabetes were included.

The overall GDM prevalence was 4%, ranging from 3.1% in Florida to 5% in Ohio. (The other five states were Nebraska, South Carolina, Utah, Washington, and New York, excluding New York City.) More than 70% of the women with GDM had a prepregnancy body mass index of at least 25 kg/m2, compared with 44.9% of the women who did not have GDM during pregnancy, Ms. Kim reported.

The GDM prevalence was 0.7% for women classified as underweight (body mass index 13-18.4 kg/m2) prior to pregnancy, 2.3% for those with normal weight (BMI 18.5-24.9), 4.8% for overweight women (25-29.9), 5.5% for those who were obese (30-34.9), and 11.5% for extremely obese women (35-64.9). With normal weight used as the reference group, the unadjusted relative risks of developing GDM were 2.1, 2.4, and 5 for women who were overweight, obese, and extremely obese, respectively.

“The probability of GDM increases with increasing BMI, with no clear BMI threshold below which a dose-response relationship was not evident,” Ms. Kim said.

The relative risks did not change after adjustment for maternal age, race/ethnicity, marital status, or parity. Once adjusted, the proportions of gestational diabetes cases attributable to overweight, obesity, and extreme obesity were 15.4%, 9.7%, and 21.1%, for a total of 46.2%. “In other words, if all women with a BMI of 25 or greater had a GDM risk equal to that of women in the normal BMI category, nearly half of GDM cases could be prevented. Lifestyle interventions to reduce BMI have the potential to lower GDM risk,” she commented.

There are a few possible reasons for why overweight/obesity contributed to only about half of GDM cases, Ms. Kim said in a follow-up interview.

“First, prepregnancy weight was self-reported, and women tend to underreport their weight. This may have led us to underestimate the contribution of overweight and obesity to the fraction of GDM attributable to weight. Also, there may be a race/ethnic difference in the relationship between BMI and GDM risk, and our analysis overrepresents non-Hispanic white women compared to the general population,” she noted.

If the analyses had been done using data representing the entire U.S. population, she continued, the study might have generated a larger estimate of the proportion of GDM cases associated with a high BMI. “Physical activity also contributes to GDM risk, and we had no data on physical activity levels in our study population. In addition, BMI is not a perfect measure of body fat, but we use it often because it can easily be obtained. If we had used lean women as our reference group, the [attributable proportion] would have been much higher. This is because the GDM risk increased in a nearly linear fashion as BMI increased.”

However, she said, the 46% estimate from this study is “higher than other non-population-based estimates found in the literature, and the dose-response relationship is consistent with estimates found in the general population with type 2 diabetes.”

Ms. Kim stated that she had no disclosures to make.

BALTIMORE — For as many as a third of adolescents who report riding in a car with a drinking driver, that driver may well be a parent rather than a peer.

That finding, based on a cross-sectional questionnaire of 2,100 adolescents, highlights “a profoundly underrecognized and undertreated public health problem,” Dr. Celeste R. Wilson said in a poster presentation at the annual meeting of the Pediatric Academic Societies.

“Primary care providers need effective counseling strategies for adolescents exposed to parents who drive while intoxicated and more training in how to deal with parents who are placing their children at risk by engaging in this behavior,” said Dr. Wilson, of the Center for Adolescent Substance Abuse Research at Children's Hospital, Boston.

The study sample was recruited from among 12- to 18-year-olds who arrived for routine primary care visits at one of nine primary care practices in Massachusetts, Vermont, and New Hampshire during 2005-2008. They completed computerized questionnaires as part of a larger study on substance abuse. The total 2,100 adolescents who completed the 20-item survey had a mean age of 16 years, and two-thirds were female. Half had at least one parent with a college degree, and 69% lived with both parents.

Of the 2,100 total respondents, 22% reported having ridden in a car in the previous 90 days with a driver who had been drinking. Of those 459 respondents, 41% identified that driver as someone living in their home. And of those 189 respondents, 91% (172) said that the drinking driver living in their home was an adult who was over 21 years of age. Because of institutional review board concerns about study subject protection, the survey did not directly inquire whether the drinking driver was a parent or guardian. Instead, the descriptions “an adult over 21 years of age” and “living in your home” were used as proxies, Dr. Wilson explained.

Adolescents who reported riding with a drinking driver who was an adult living in their home were more likely to be female, to be white, and to have a parent with no college degree. Younger adolescents were more likely than older ones to report riding with a drinking “parent.”

Although the exact nature of the relationship between the adult drinking driver and the adolescent could not be confirmed, other questionnaire data supported the supposition that most of these were indeed parents. The risk for having ridden with a drinking driver who was older than 21 and living in the teenager's home was more than three times greater for those who agreed with the statements “I have a parent whose use of alcohol or other drugs worries me,” “I have a parent who gets drunk or high,” and/or “I have a parent who needs treatment for alcohol or other drug problems.” The risk was more than double for those who said, “I have a parent who uses alcohol or drugs soon after getting up in the morning.”

Still, Dr. Wilson acknowledged that at least in some cases, the drinking driver might be an older sibling or a parent's romantic partner who is not the teen's parent. Nonetheless, “I think the key issue is that an adult who is well known to the adolescent is engaging in behavior that's potentially putting the adolescent at risk. Such behavior is of grave concern, as it not only threatens the adolescent's safety but also inadvertently sends a powerful yet erroneous message that it is acceptable to drink and drive.”

This study was funded by grants from the National Institutes of Health and several private foundations. Dr. Wilson said she had no financial disclosures.

Clinicians need counseling strategies for teens who are exposed to parents who drink and drive. ©Dmitriy

BALTIMORE — For as many as a third of adolescents who report riding in a car with a drinking driver, that driver may well be a parent rather than a peer.

That finding, based on a cross-sectional questionnaire of 2,100 adolescents, highlights “a profoundly underrecognized and undertreated public health problem,” Dr. Celeste R. Wilson said in a poster presentation at the annual meeting of the Pediatric Academic Societies.

“Primary care providers need effective counseling strategies for adolescents exposed to parents who drive while intoxicated and more training in how to deal with parents who are placing their children at risk by engaging in this behavior,” said Dr. Wilson, of the Center for Adolescent Substance Abuse Research at Children's Hospital, Boston.

The study sample was recruited from among 12- to 18-year-olds who arrived for routine primary care visits at one of nine primary care practices in Massachusetts, Vermont, and New Hampshire during 2005-2008. They completed computerized questionnaires as part of a larger study on substance abuse. The total 2,100 adolescents who completed the 20-item survey had a mean age of 16 years, and two-thirds were female. Half had at least one parent with a college degree, and 69% lived with both parents.

Of the 2,100 total respondents, 22% reported having ridden in a car in the previous 90 days with a driver who had been drinking. Of those 459 respondents, 41% identified that driver as someone living in their home. And of those 189 respondents, 91% (172) said that the drinking driver living in their home was an adult who was over 21 years of age. Because of institutional review board concerns about study subject protection, the survey did not directly inquire whether the drinking driver was a parent or guardian. Instead, the descriptions “an adult over 21 years of age” and “living in your home” were used as proxies, Dr. Wilson explained.

Adolescents who reported riding with a drinking driver who was an adult living in their home were more likely to be female, to be white, and to have a parent with no college degree. Younger adolescents were more likely than older ones to report riding with a drinking “parent.”

Although the exact nature of the relationship between the adult drinking driver and the adolescent could not be confirmed, other questionnaire data supported the supposition that most of these were indeed parents. The risk for having ridden with a drinking driver who was older than 21 and living in the teenager's home was more than three times greater for those who agreed with the statements “I have a parent whose use of alcohol or other drugs worries me,” “I have a parent who gets drunk or high,” and/or “I have a parent who needs treatment for alcohol or other drug problems.” The risk was more than double for those who said, “I have a parent who uses alcohol or drugs soon after getting up in the morning.”

Still, Dr. Wilson acknowledged that at least in some cases, the drinking driver might be an older sibling or a parent's romantic partner who is not the teen's parent. Nonetheless, “I think the key issue is that an adult who is well known to the adolescent is engaging in behavior that's potentially putting the adolescent at risk. Such behavior is of grave concern, as it not only threatens the adolescent's safety but also inadvertently sends a powerful yet erroneous message that it is acceptable to drink and drive.”

This study was funded by grants from the National Institutes of Health and several private foundations. Dr. Wilson said she had no financial disclosures.

Clinicians need counseling strategies for teens who are exposed to parents who drink and drive. ©Dmitriy

BALTIMORE — For as many as a third of adolescents who report riding in a car with a drinking driver, that driver may well be a parent rather than a peer.

That finding, based on a cross-sectional questionnaire of 2,100 adolescents, highlights “a profoundly underrecognized and undertreated public health problem,” Dr. Celeste R. Wilson said in a poster presentation at the annual meeting of the Pediatric Academic Societies.

“Primary care providers need effective counseling strategies for adolescents exposed to parents who drive while intoxicated and more training in how to deal with parents who are placing their children at risk by engaging in this behavior,” said Dr. Wilson, of the Center for Adolescent Substance Abuse Research at Children's Hospital, Boston.

The study sample was recruited from among 12- to 18-year-olds who arrived for routine primary care visits at one of nine primary care practices in Massachusetts, Vermont, and New Hampshire during 2005-2008. They completed computerized questionnaires as part of a larger study on substance abuse. The total 2,100 adolescents who completed the 20-item survey had a mean age of 16 years, and two-thirds were female. Half had at least one parent with a college degree, and 69% lived with both parents.

Of the 2,100 total respondents, 22% reported having ridden in a car in the previous 90 days with a driver who had been drinking. Of those 459 respondents, 41% identified that driver as someone living in their home. And of those 189 respondents, 91% (172) said that the drinking driver living in their home was an adult who was over 21 years of age. Because of institutional review board concerns about study subject protection, the survey did not directly inquire whether the drinking driver was a parent or guardian. Instead, the descriptions “an adult over 21 years of age” and “living in your home” were used as proxies, Dr. Wilson explained.

Adolescents who reported riding with a drinking driver who was an adult living in their home were more likely to be female, to be white, and to have a parent with no college degree. Younger adolescents were more likely than older ones to report riding with a drinking “parent.”

Although the exact nature of the relationship between the adult drinking driver and the adolescent could not be confirmed, other questionnaire data supported the supposition that most of these were indeed parents. The risk for having ridden with a drinking driver who was older than 21 and living in the teenager's home was more than three times greater for those who agreed with the statements “I have a parent whose use of alcohol or other drugs worries me,” “I have a parent who gets drunk or high,” and/or “I have a parent who needs treatment for alcohol or other drug problems.” The risk was more than double for those who said, “I have a parent who uses alcohol or drugs soon after getting up in the morning.”

Still, Dr. Wilson acknowledged that at least in some cases, the drinking driver might be an older sibling or a parent's romantic partner who is not the teen's parent. Nonetheless, “I think the key issue is that an adult who is well known to the adolescent is engaging in behavior that's potentially putting the adolescent at risk. Such behavior is of grave concern, as it not only threatens the adolescent's safety but also inadvertently sends a powerful yet erroneous message that it is acceptable to drink and drive.”

This study was funded by grants from the National Institutes of Health and several private foundations. Dr. Wilson said she had no financial disclosures.

Clinicians need counseling strategies for teens who are exposed to parents who drink and drive. ©Dmitriy

HOUSTON — Ultrasound was useful in the long-term postoperative follow-up of thyroid cancer in a review of 398 ultrasounds performed in 191 patients.

The findings suggest that patients with suspicious ultrasounds should undergo fine-needle aspiration (FNA) biopsies, while those with equivocal ultrasounds can be observed and undergo a follow-up ultrasound in 6–12 months, Dr. Adrian Harvey of the Cleveland Clinic said at the annual meeting of the American Association of Clinical Endocrinologists.

Sonographic findings were classified as normal, suspicious, or equivocal. A normal ultrasound was one with no concerning features in the lymph nodes. Criteria for suspicious ultrasound included two or more abnormal lymph node features. An equivocal ultrasound was determined based on the presence of one suspicious feature and clinician judgment.

Of 172 ultrasounds done on patients with positive tumor markers, 41% had suspicious findings, 10% had equivocal findings, and 49% were normal. Recurrence was confirmed in 61 of 70 suspicious ultrasounds (87%), compared with just 6 of 18 (33%) with equivocal findings and none of the 85 with normal findings. Over a mean follow-up of 13 months, eight of the patients whose ultrasound findings were originally deemed normal developed cervical recurrence.

Among the 125 total abnormal ultrasound findings, 60% were located in a reoperative field. There were no significant differences between the rates of positive FNA or equivocal ultrasound between reoperative and nonoperative fields.

Dr. Harvey stated that he had no conflicts of interest to disclose.

HOUSTON — Ultrasound was useful in the long-term postoperative follow-up of thyroid cancer in a review of 398 ultrasounds performed in 191 patients.

The findings suggest that patients with suspicious ultrasounds should undergo fine-needle aspiration (FNA) biopsies, while those with equivocal ultrasounds can be observed and undergo a follow-up ultrasound in 6–12 months, Dr. Adrian Harvey of the Cleveland Clinic said at the annual meeting of the American Association of Clinical Endocrinologists.

Sonographic findings were classified as normal, suspicious, or equivocal. A normal ultrasound was one with no concerning features in the lymph nodes. Criteria for suspicious ultrasound included two or more abnormal lymph node features. An equivocal ultrasound was determined based on the presence of one suspicious feature and clinician judgment.

Of 172 ultrasounds done on patients with positive tumor markers, 41% had suspicious findings, 10% had equivocal findings, and 49% were normal. Recurrence was confirmed in 61 of 70 suspicious ultrasounds (87%), compared with just 6 of 18 (33%) with equivocal findings and none of the 85 with normal findings. Over a mean follow-up of 13 months, eight of the patients whose ultrasound findings were originally deemed normal developed cervical recurrence.

Among the 125 total abnormal ultrasound findings, 60% were located in a reoperative field. There were no significant differences between the rates of positive FNA or equivocal ultrasound between reoperative and nonoperative fields.

Dr. Harvey stated that he had no conflicts of interest to disclose.

HOUSTON — Ultrasound was useful in the long-term postoperative follow-up of thyroid cancer in a review of 398 ultrasounds performed in 191 patients.

The findings suggest that patients with suspicious ultrasounds should undergo fine-needle aspiration (FNA) biopsies, while those with equivocal ultrasounds can be observed and undergo a follow-up ultrasound in 6–12 months, Dr. Adrian Harvey of the Cleveland Clinic said at the annual meeting of the American Association of Clinical Endocrinologists.

Sonographic findings were classified as normal, suspicious, or equivocal. A normal ultrasound was one with no concerning features in the lymph nodes. Criteria for suspicious ultrasound included two or more abnormal lymph node features. An equivocal ultrasound was determined based on the presence of one suspicious feature and clinician judgment.

Of 172 ultrasounds done on patients with positive tumor markers, 41% had suspicious findings, 10% had equivocal findings, and 49% were normal. Recurrence was confirmed in 61 of 70 suspicious ultrasounds (87%), compared with just 6 of 18 (33%) with equivocal findings and none of the 85 with normal findings. Over a mean follow-up of 13 months, eight of the patients whose ultrasound findings were originally deemed normal developed cervical recurrence.

Among the 125 total abnormal ultrasound findings, 60% were located in a reoperative field. There were no significant differences between the rates of positive FNA or equivocal ultrasound between reoperative and nonoperative fields.

Dr. Harvey stated that he had no conflicts of interest to disclose.

HOUSTON — Colesevelam maintained its glucose-lowering effect up to 78 weeks in an open-label extension study involving 146 patients with type 2 diabetes who were also taking metformin.

Colesevelam (Welchol) is a bile acid sequestrant approved for both glycemic control in adults with type 2 diabetes and lowering low-density-lipoprotein cholesterol levels in adults with primary hypercholesterolemia, Dr. Harold E. Bays and his colleagues said in a poster presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Subjects with type 2 diabetes who completed one of three previous26-week randomized, double-blind, placebo-controlled trials evaluating colesevelam in combination with metformin, insulin, or sulfonylurea were invited to join the 52-week open-label extension study.

All received 3.8 g/day of colesevelam (as six 625-mg tablets), taken either once a day with dinner (six tablets) or twice a day (three tablets with lunch and three with dinner). Patients were given the choice of schedule. All had been previously taking metformin, and continued to take it through the extension study. Doses could be adjusted, however, and other glucose-lowering agents could also be added with the aim of achieving a hemoglobin A_1c of less than 7%, said Dr. Bays of the Louisville (Ky.) Metabolic and Atherosclerosis Research Center and his associates.

A total of 222 patients completed the initial randomized, controlled study, and 146 enrolled in the open-label extension. Of those, 81 had received colesevelam in the randomized study and 65 were on placebo (both in combination with metformin). Of those, 56 and 41, respectively, completed the open-label extension.

At the end of the initial 26 weeks, HbA_1c levels had dropped from a mean of 8.2% to 7.6% in the colesevelam group, while remaining nearly unchanged in the placebo group (8.1% to 8.2%). These HbA_1c levels were maintained over the 52-week extension in the group that had been taking colesevelam the entire 78 weeks, with a final HbA_1c of 7.7%.

Those who had been on placebo during the randomized study and were now taking colesevelam achieved a mean HbA_1c value of 7.4% by the end of the 52-week extension.

Nine patients discontinued the entire study because of adverse events, including three serious events. Nonserious events deemed possibly or probably related to colesevelam included wheezing, dyspnea, and cough in one patient, abnormal liver function test in one, and dyspepsia in two.

Of 15 serious events reported, 13 were deemed not related to the study drug and two were considered unlikely to be related. Overall compliance in all phases of the study was 88.5%, the investigators reported.

The study was funded by Daiichi Sankyo Inc., which markets colesevelam.

HOUSTON — Colesevelam maintained its glucose-lowering effect up to 78 weeks in an open-label extension study involving 146 patients with type 2 diabetes who were also taking metformin.

Colesevelam (Welchol) is a bile acid sequestrant approved for both glycemic control in adults with type 2 diabetes and lowering low-density-lipoprotein cholesterol levels in adults with primary hypercholesterolemia, Dr. Harold E. Bays and his colleagues said in a poster presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Subjects with type 2 diabetes who completed one of three previous26-week randomized, double-blind, placebo-controlled trials evaluating colesevelam in combination with metformin, insulin, or sulfonylurea were invited to join the 52-week open-label extension study.

All received 3.8 g/day of colesevelam (as six 625-mg tablets), taken either once a day with dinner (six tablets) or twice a day (three tablets with lunch and three with dinner). Patients were given the choice of schedule. All had been previously taking metformin, and continued to take it through the extension study. Doses could be adjusted, however, and other glucose-lowering agents could also be added with the aim of achieving a hemoglobin A_1c of less than 7%, said Dr. Bays of the Louisville (Ky.) Metabolic and Atherosclerosis Research Center and his associates.

A total of 222 patients completed the initial randomized, controlled study, and 146 enrolled in the open-label extension. Of those, 81 had received colesevelam in the randomized study and 65 were on placebo (both in combination with metformin). Of those, 56 and 41, respectively, completed the open-label extension.

At the end of the initial 26 weeks, HbA_1c levels had dropped from a mean of 8.2% to 7.6% in the colesevelam group, while remaining nearly unchanged in the placebo group (8.1% to 8.2%). These HbA_1c levels were maintained over the 52-week extension in the group that had been taking colesevelam the entire 78 weeks, with a final HbA_1c of 7.7%.

Those who had been on placebo during the randomized study and were now taking colesevelam achieved a mean HbA_1c value of 7.4% by the end of the 52-week extension.

Nine patients discontinued the entire study because of adverse events, including three serious events. Nonserious events deemed possibly or probably related to colesevelam included wheezing, dyspnea, and cough in one patient, abnormal liver function test in one, and dyspepsia in two.

Of 15 serious events reported, 13 were deemed not related to the study drug and two were considered unlikely to be related. Overall compliance in all phases of the study was 88.5%, the investigators reported.

The study was funded by Daiichi Sankyo Inc., which markets colesevelam.

HOUSTON — Colesevelam maintained its glucose-lowering effect up to 78 weeks in an open-label extension study involving 146 patients with type 2 diabetes who were also taking metformin.

Colesevelam (Welchol) is a bile acid sequestrant approved for both glycemic control in adults with type 2 diabetes and lowering low-density-lipoprotein cholesterol levels in adults with primary hypercholesterolemia, Dr. Harold E. Bays and his colleagues said in a poster presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Subjects with type 2 diabetes who completed one of three previous26-week randomized, double-blind, placebo-controlled trials evaluating colesevelam in combination with metformin, insulin, or sulfonylurea were invited to join the 52-week open-label extension study.

All received 3.8 g/day of colesevelam (as six 625-mg tablets), taken either once a day with dinner (six tablets) or twice a day (three tablets with lunch and three with dinner). Patients were given the choice of schedule. All had been previously taking metformin, and continued to take it through the extension study. Doses could be adjusted, however, and other glucose-lowering agents could also be added with the aim of achieving a hemoglobin A_1c of less than 7%, said Dr. Bays of the Louisville (Ky.) Metabolic and Atherosclerosis Research Center and his associates.

A total of 222 patients completed the initial randomized, controlled study, and 146 enrolled in the open-label extension. Of those, 81 had received colesevelam in the randomized study and 65 were on placebo (both in combination with metformin). Of those, 56 and 41, respectively, completed the open-label extension.

At the end of the initial 26 weeks, HbA_1c levels had dropped from a mean of 8.2% to 7.6% in the colesevelam group, while remaining nearly unchanged in the placebo group (8.1% to 8.2%). These HbA_1c levels were maintained over the 52-week extension in the group that had been taking colesevelam the entire 78 weeks, with a final HbA_1c of 7.7%.

Those who had been on placebo during the randomized study and were now taking colesevelam achieved a mean HbA_1c value of 7.4% by the end of the 52-week extension.

Nine patients discontinued the entire study because of adverse events, including three serious events. Nonserious events deemed possibly or probably related to colesevelam included wheezing, dyspnea, and cough in one patient, abnormal liver function test in one, and dyspepsia in two.

Of 15 serious events reported, 13 were deemed not related to the study drug and two were considered unlikely to be related. Overall compliance in all phases of the study was 88.5%, the investigators reported.

The study was funded by Daiichi Sankyo Inc., which markets colesevelam.

Diabetic patients with atrial fibrillation obtained greater absolute benefits from BP-lowering treatment than did those without in a study of more than 11,000 patients with type 2 diabetes.

The study findings suggest that an estimated 5 years of active blood pressure-lowering treatment would prevent one cardiovascular death among every 42 patients with atrial fibrillation (AF) at baseline, compared with one death among 120 patients without AF, said Dr. Xin Du of the University of Sydney, and associates (Eur. Heart J. 2009 March 12 [doi:10.1093/eurheartj/ehp055

AF was present at baseline in 847 (7.6%) of the 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study, which was jointly funded by the National Health and Medical Research Council of Australia and Servier, France. The outcomes measured were all-cause mortality cardiovascular death, MI, stroke, and heart failure.

Over a mean follow-up of 4.3 years, 879 patients died. Of those deaths, 468 (53%) were due to cardiovascular causes and 15% of the total deaths occurred in patients with AF. Patients with AF at baseline had significantly higher rates of both all-cause and cardiovascular mortality, at 3.9% and 2.4%, respectively, than did those who did not have AF, whose all cause and cardiovascular mortality rates were 1.7% and 0.9%, respectively.

After adjustment for covariates, those hazard ratios were 1.61 and 1.77, respectively. Patients with AF also had higher risk of major cerebrovascular events, with a hazard ratio of 1.68 that was similar for ischemic and hemorrhagic subtypes, reported the authors, several of whom other than Dr. Du have received lecture fees or grant support from, or served on an advisory board for, Servier.

Diabetic patients with atrial fibrillation obtained greater absolute benefits from BP-lowering treatment than did those without in a study of more than 11,000 patients with type 2 diabetes.

The study findings suggest that an estimated 5 years of active blood pressure-lowering treatment would prevent one cardiovascular death among every 42 patients with atrial fibrillation (AF) at baseline, compared with one death among 120 patients without AF, said Dr. Xin Du of the University of Sydney, and associates (Eur. Heart J. 2009 March 12 [doi:10.1093/eurheartj/ehp055

AF was present at baseline in 847 (7.6%) of the 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study, which was jointly funded by the National Health and Medical Research Council of Australia and Servier, France. The outcomes measured were all-cause mortality cardiovascular death, MI, stroke, and heart failure.

Over a mean follow-up of 4.3 years, 879 patients died. Of those deaths, 468 (53%) were due to cardiovascular causes and 15% of the total deaths occurred in patients with AF. Patients with AF at baseline had significantly higher rates of both all-cause and cardiovascular mortality, at 3.9% and 2.4%, respectively, than did those who did not have AF, whose all cause and cardiovascular mortality rates were 1.7% and 0.9%, respectively.

After adjustment for covariates, those hazard ratios were 1.61 and 1.77, respectively. Patients with AF also had higher risk of major cerebrovascular events, with a hazard ratio of 1.68 that was similar for ischemic and hemorrhagic subtypes, reported the authors, several of whom other than Dr. Du have received lecture fees or grant support from, or served on an advisory board for, Servier.

Diabetic patients with atrial fibrillation obtained greater absolute benefits from BP-lowering treatment than did those without in a study of more than 11,000 patients with type 2 diabetes.

The study findings suggest that an estimated 5 years of active blood pressure-lowering treatment would prevent one cardiovascular death among every 42 patients with atrial fibrillation (AF) at baseline, compared with one death among 120 patients without AF, said Dr. Xin Du of the University of Sydney, and associates (Eur. Heart J. 2009 March 12 [doi:10.1093/eurheartj/ehp055

AF was present at baseline in 847 (7.6%) of the 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study, which was jointly funded by the National Health and Medical Research Council of Australia and Servier, France. The outcomes measured were all-cause mortality cardiovascular death, MI, stroke, and heart failure.

Over a mean follow-up of 4.3 years, 879 patients died. Of those deaths, 468 (53%) were due to cardiovascular causes and 15% of the total deaths occurred in patients with AF. Patients with AF at baseline had significantly higher rates of both all-cause and cardiovascular mortality, at 3.9% and 2.4%, respectively, than did those who did not have AF, whose all cause and cardiovascular mortality rates were 1.7% and 0.9%, respectively.

After adjustment for covariates, those hazard ratios were 1.61 and 1.77, respectively. Patients with AF also had higher risk of major cerebrovascular events, with a hazard ratio of 1.68 that was similar for ischemic and hemorrhagic subtypes, reported the authors, several of whom other than Dr. Du have received lecture fees or grant support from, or served on an advisory board for, Servier.