Miriam E. Tucker

WASHINGTON — Obese female patients should be screened for urinary incontinence, particularly if they have diabetes, Jean M. Lawrence, Sc.D., reported in a poster at the annual scientific sessions of the American Diabetes Association.

A community-based survey of 4,237 women aged 25–84 years revealed significantly increased rates of three major forms of incontinence among women who were obese and had diabetes, reported Dr. Lawrence, of Kaiser Permanente Southern California, Pasadena, and her associates.

The women had a median age of 58 years. They were 60% white, 20% Hispanic, 10% black, 8% Asian, and 2% race unknown. Overall, 15% had stress urinary incontinence (SUI), 13% had overactive bladder (OAB), and 25% had anal incontinence (AI). In addition, 11% had diabetes, of whom 21% used insulin. The women with diabetes were older (64.6 years vs. 56.1 years), were more likely to be menopausal (85.8% vs. 64.4%), and to be obese (54.9% vs. 23.8%).

Of the 472 women with diabetes, 23.2% had SUI, compared with 14.1% of the 3,765 women without diabetes. OAB was also significantly more common among those with diabetes (21.6% vs. 12.4%), as was AI (32.4% vs. 24.3%).

Women who were both obese and had diabetes had adjusted odds ratios of 3.2 for SUI, 3.1 for OAB, and 1.8 for AI, compared with women who did not have either condition. Women who were obese but did not have diabetes had the next highest risk, with odds ratios of 2.45 for SUI, 2.79 for OAB, and 1.45 for AI. Among the nonobese women with diabetes (both insulin users and nonusers), the only significantly elevated risk was for SUI, with an odds ratio of 1.55, Dr. Lawrence and her associates reported.

WASHINGTON — Obese female patients should be screened for urinary incontinence, particularly if they have diabetes, Jean M. Lawrence, Sc.D., reported in a poster at the annual scientific sessions of the American Diabetes Association.

A community-based survey of 4,237 women aged 25–84 years revealed significantly increased rates of three major forms of incontinence among women who were obese and had diabetes, reported Dr. Lawrence, of Kaiser Permanente Southern California, Pasadena, and her associates.

The women had a median age of 58 years. They were 60% white, 20% Hispanic, 10% black, 8% Asian, and 2% race unknown. Overall, 15% had stress urinary incontinence (SUI), 13% had overactive bladder (OAB), and 25% had anal incontinence (AI). In addition, 11% had diabetes, of whom 21% used insulin. The women with diabetes were older (64.6 years vs. 56.1 years), were more likely to be menopausal (85.8% vs. 64.4%), and to be obese (54.9% vs. 23.8%).

Of the 472 women with diabetes, 23.2% had SUI, compared with 14.1% of the 3,765 women without diabetes. OAB was also significantly more common among those with diabetes (21.6% vs. 12.4%), as was AI (32.4% vs. 24.3%).

Women who were both obese and had diabetes had adjusted odds ratios of 3.2 for SUI, 3.1 for OAB, and 1.8 for AI, compared with women who did not have either condition. Women who were obese but did not have diabetes had the next highest risk, with odds ratios of 2.45 for SUI, 2.79 for OAB, and 1.45 for AI. Among the nonobese women with diabetes (both insulin users and nonusers), the only significantly elevated risk was for SUI, with an odds ratio of 1.55, Dr. Lawrence and her associates reported.

WASHINGTON — Obese female patients should be screened for urinary incontinence, particularly if they have diabetes, Jean M. Lawrence, Sc.D., reported in a poster at the annual scientific sessions of the American Diabetes Association.

A community-based survey of 4,237 women aged 25–84 years revealed significantly increased rates of three major forms of incontinence among women who were obese and had diabetes, reported Dr. Lawrence, of Kaiser Permanente Southern California, Pasadena, and her associates.

The women had a median age of 58 years. They were 60% white, 20% Hispanic, 10% black, 8% Asian, and 2% race unknown. Overall, 15% had stress urinary incontinence (SUI), 13% had overactive bladder (OAB), and 25% had anal incontinence (AI). In addition, 11% had diabetes, of whom 21% used insulin. The women with diabetes were older (64.6 years vs. 56.1 years), were more likely to be menopausal (85.8% vs. 64.4%), and to be obese (54.9% vs. 23.8%).

Of the 472 women with diabetes, 23.2% had SUI, compared with 14.1% of the 3,765 women without diabetes. OAB was also significantly more common among those with diabetes (21.6% vs. 12.4%), as was AI (32.4% vs. 24.3%).

Women who were both obese and had diabetes had adjusted odds ratios of 3.2 for SUI, 3.1 for OAB, and 1.8 for AI, compared with women who did not have either condition. Women who were obese but did not have diabetes had the next highest risk, with odds ratios of 2.45 for SUI, 2.79 for OAB, and 1.45 for AI. Among the nonobese women with diabetes (both insulin users and nonusers), the only significantly elevated risk was for SUI, with an odds ratio of 1.55, Dr. Lawrence and her associates reported.

OUR LUCAYA, BAHAMAS — Merkel cell carcinoma is more deadly than melanoma, and it is almost always misdiagnosed clinically, Dr. Henry W. Randle said at a meeting of the American Society for Mohs Surgery.

In a recent survey of 135 biopsy-confirmed Merkel cell carcinomas, 44% had been judged clinically to be cysts or acneiform lesions, 19% to be other nonmelanoma skin cancers, 9% to be dermatofibrosarcoma protuberans, and 28% received various other misdiagnoses. Just 2 of the 135 were accurately identified as Merkel cell carcinoma prior to biopsy. “Clinically, it's a problem. Almost no one identifies these up front. Keep it in mind in your differential,” said Dr. Randle of the Mayo Clinic in Jacksonville, Fla.

Indeed, Merkel cell carcinoma's clinical presentation is very nonspecific, consisting of firm, red to purple, nontender papules or nodules usually appearing on sun-damaged skin. Patients are typically over 65 years of age, with incidence about equal in men and women. Those who are severely immunosuppressed or who have undergone psoralen-ultraviolet-light (PUVA) treatment are at increased risk.

Although Merkel cell carcinoma is uncommon, its incidence tripled between 1986 and 2001, going from 0.15 per 100,000 age-adjusted population to 0.44/100,000 (J. Surg. Oncol. 2005;89:1–4). Absolute numbers are hard to obtain, but estimates range from 400 to 800 cases per year in the United States, he said.

Mortality is 25% within the first 3 years. However, patients who survive past 3 years are not likely to die of the disease. Survival is highly dependent on stage at diagnosis: Those with localized disease and lesions of less than 2 cm in diameter (stage 1) have a 90% survival rate at 3 years, whereas larger localized lesions (stage 2) reduce 3-year survival to 70%. Nodal disease (stage 3) reduces survival to just 30%, and metastatic disease (stage 4) kills 90%.

Sentinel lymph node biopsy (SLNB) should be performed routinely in these patients, because clinical examination is insufficient: In one study, 10 of 31 patients without palpable lymph nodes had a positive SLNB. Adjuvant treatment should be considered in all Merkel cell carcinoma patients with positive lymph nodes, Dr. Randle advised.

Treatment of the primary lesion involves either Mohs or wide (1–3 cm) excision. Dr. Randle tends not to use Mohs, however, because surgeons prefer to do both procedures at once rather than taking the node after the dermatologist has already operated on the cancer. “I usually send for wide excision and [SLNB], but you can use Mohs,” he noted.

Currently, radiation is the adjuvant treatment of choice for patients with positive sentinel nodes, while data on chemotherapy are less definitive. In one study, the addition of radiation to surgery, compared with surgery alone, resulted in lower rates of local recurrence (3% vs. 25%), nodal recurrence (22% vs. 42%), and distant spread (11% vs. 21%). “It's been questioned in the literature, but I think radiation clearly does help,” Dr. Randle remarked.

The risk for Merkel cell carcinoma is elevated 100-fold among individuals who have had PUVA treatment (N. Engl. J. Med. 1998;339:1247–8). For more information, visit www.merkelcell.org

The lesions tend to be nonspecific, consisting of firm, red to purple, nontender papules or nodules. Courtesy Dr. Henry W. Randle

OUR LUCAYA, BAHAMAS — Merkel cell carcinoma is more deadly than melanoma, and it is almost always misdiagnosed clinically, Dr. Henry W. Randle said at a meeting of the American Society for Mohs Surgery.

In a recent survey of 135 biopsy-confirmed Merkel cell carcinomas, 44% had been judged clinically to be cysts or acneiform lesions, 19% to be other nonmelanoma skin cancers, 9% to be dermatofibrosarcoma protuberans, and 28% received various other misdiagnoses. Just 2 of the 135 were accurately identified as Merkel cell carcinoma prior to biopsy. “Clinically, it's a problem. Almost no one identifies these up front. Keep it in mind in your differential,” said Dr. Randle of the Mayo Clinic in Jacksonville, Fla.

Indeed, Merkel cell carcinoma's clinical presentation is very nonspecific, consisting of firm, red to purple, nontender papules or nodules usually appearing on sun-damaged skin. Patients are typically over 65 years of age, with incidence about equal in men and women. Those who are severely immunosuppressed or who have undergone psoralen-ultraviolet-light (PUVA) treatment are at increased risk.

Although Merkel cell carcinoma is uncommon, its incidence tripled between 1986 and 2001, going from 0.15 per 100,000 age-adjusted population to 0.44/100,000 (J. Surg. Oncol. 2005;89:1–4). Absolute numbers are hard to obtain, but estimates range from 400 to 800 cases per year in the United States, he said.

Mortality is 25% within the first 3 years. However, patients who survive past 3 years are not likely to die of the disease. Survival is highly dependent on stage at diagnosis: Those with localized disease and lesions of less than 2 cm in diameter (stage 1) have a 90% survival rate at 3 years, whereas larger localized lesions (stage 2) reduce 3-year survival to 70%. Nodal disease (stage 3) reduces survival to just 30%, and metastatic disease (stage 4) kills 90%.

Sentinel lymph node biopsy (SLNB) should be performed routinely in these patients, because clinical examination is insufficient: In one study, 10 of 31 patients without palpable lymph nodes had a positive SLNB. Adjuvant treatment should be considered in all Merkel cell carcinoma patients with positive lymph nodes, Dr. Randle advised.

Treatment of the primary lesion involves either Mohs or wide (1–3 cm) excision. Dr. Randle tends not to use Mohs, however, because surgeons prefer to do both procedures at once rather than taking the node after the dermatologist has already operated on the cancer. “I usually send for wide excision and [SLNB], but you can use Mohs,” he noted.

Currently, radiation is the adjuvant treatment of choice for patients with positive sentinel nodes, while data on chemotherapy are less definitive. In one study, the addition of radiation to surgery, compared with surgery alone, resulted in lower rates of local recurrence (3% vs. 25%), nodal recurrence (22% vs. 42%), and distant spread (11% vs. 21%). “It's been questioned in the literature, but I think radiation clearly does help,” Dr. Randle remarked.

The risk for Merkel cell carcinoma is elevated 100-fold among individuals who have had PUVA treatment (N. Engl. J. Med. 1998;339:1247–8). For more information, visit www.merkelcell.org

The lesions tend to be nonspecific, consisting of firm, red to purple, nontender papules or nodules. Courtesy Dr. Henry W. Randle

OUR LUCAYA, BAHAMAS — Merkel cell carcinoma is more deadly than melanoma, and it is almost always misdiagnosed clinically, Dr. Henry W. Randle said at a meeting of the American Society for Mohs Surgery.

In a recent survey of 135 biopsy-confirmed Merkel cell carcinomas, 44% had been judged clinically to be cysts or acneiform lesions, 19% to be other nonmelanoma skin cancers, 9% to be dermatofibrosarcoma protuberans, and 28% received various other misdiagnoses. Just 2 of the 135 were accurately identified as Merkel cell carcinoma prior to biopsy. “Clinically, it's a problem. Almost no one identifies these up front. Keep it in mind in your differential,” said Dr. Randle of the Mayo Clinic in Jacksonville, Fla.

Indeed, Merkel cell carcinoma's clinical presentation is very nonspecific, consisting of firm, red to purple, nontender papules or nodules usually appearing on sun-damaged skin. Patients are typically over 65 years of age, with incidence about equal in men and women. Those who are severely immunosuppressed or who have undergone psoralen-ultraviolet-light (PUVA) treatment are at increased risk.

Although Merkel cell carcinoma is uncommon, its incidence tripled between 1986 and 2001, going from 0.15 per 100,000 age-adjusted population to 0.44/100,000 (J. Surg. Oncol. 2005;89:1–4). Absolute numbers are hard to obtain, but estimates range from 400 to 800 cases per year in the United States, he said.

Mortality is 25% within the first 3 years. However, patients who survive past 3 years are not likely to die of the disease. Survival is highly dependent on stage at diagnosis: Those with localized disease and lesions of less than 2 cm in diameter (stage 1) have a 90% survival rate at 3 years, whereas larger localized lesions (stage 2) reduce 3-year survival to 70%. Nodal disease (stage 3) reduces survival to just 30%, and metastatic disease (stage 4) kills 90%.

Sentinel lymph node biopsy (SLNB) should be performed routinely in these patients, because clinical examination is insufficient: In one study, 10 of 31 patients without palpable lymph nodes had a positive SLNB. Adjuvant treatment should be considered in all Merkel cell carcinoma patients with positive lymph nodes, Dr. Randle advised.

Treatment of the primary lesion involves either Mohs or wide (1–3 cm) excision. Dr. Randle tends not to use Mohs, however, because surgeons prefer to do both procedures at once rather than taking the node after the dermatologist has already operated on the cancer. “I usually send for wide excision and [SLNB], but you can use Mohs,” he noted.

Currently, radiation is the adjuvant treatment of choice for patients with positive sentinel nodes, while data on chemotherapy are less definitive. In one study, the addition of radiation to surgery, compared with surgery alone, resulted in lower rates of local recurrence (3% vs. 25%), nodal recurrence (22% vs. 42%), and distant spread (11% vs. 21%). “It's been questioned in the literature, but I think radiation clearly does help,” Dr. Randle remarked.

The risk for Merkel cell carcinoma is elevated 100-fold among individuals who have had PUVA treatment (N. Engl. J. Med. 1998;339:1247–8). For more information, visit www.merkelcell.org

The lesions tend to be nonspecific, consisting of firm, red to purple, nontender papules or nodules. Courtesy Dr. Henry W. Randle

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease caused by Neisseria meningitis serogroups A, C, Y, and W-135. In May 2005, the CDC published ACIP's recommendation for its routine use in 11- to 12-year-olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

After the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11- to 12- year-olds, but for continuation of immunization in the other recommended groups. The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply (MMWR 2006;55:567–8).

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease caused by Neisseria meningitis serogroups A, C, Y, and W-135. In May 2005, the CDC published ACIP's recommendation for its routine use in 11- to 12-year-olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

After the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11- to 12- year-olds, but for continuation of immunization in the other recommended groups. The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply (MMWR 2006;55:567–8).

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease caused by Neisseria meningitis serogroups A, C, Y, and W-135. In May 2005, the CDC published ACIP's recommendation for its routine use in 11- to 12-year-olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

After the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11- to 12- year-olds, but for continuation of immunization in the other recommended groups. The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply (MMWR 2006;55:567–8).

ATLANTA — The prioritization plan for use of inactivated influenza vaccine in the event of a supply shortage or delay has been updated to reflect the recently designated high-risk status of children aged 24–59 months.

The vote, of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting, must be approved by CDC and published before it becomes official. If approved, the new prioritization scheme will look like this:

Tier 1

1A

Persons aged 65 years and older with comorbid conditions

Residents of long-term care facilities

1B

Persons aged 2–64 years with comorbid conditions

Persons aged 65 years and older without comorbid conditions

Children aged 6–23 months

Pregnant women

1C

Children aged 24–59 months

Health care personnel

Household contacts and out-of-home caregivers of children aged less than 6 months

Tier 2

Household contacts of children and adults at increased risk for influenza-related complications

Healthy persons aged 50–64 years

Tier 3

Persons aged 5–49 years without high-risk conditions

In most vaccine shortfall situations, all three groups in tier 1 can be considered top priority, followed by tiers 2 and 3. It would be necessary to further prioritize risk groups 1A, 1B, and 1C separately only on rare occasions when the supply is extremely limited, Nicole M. Smith, Ph.D., said at the meeting. More information about the use of influenza vaccine and antiviral agents is available at

www.cdc.gov/mmwr/preview/mmwrhtml/rr55e628a1.htm

ATLANTA — The prioritization plan for use of inactivated influenza vaccine in the event of a supply shortage or delay has been updated to reflect the recently designated high-risk status of children aged 24–59 months.

The vote, of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting, must be approved by CDC and published before it becomes official. If approved, the new prioritization scheme will look like this:

Tier 1

1A

Persons aged 65 years and older with comorbid conditions

Residents of long-term care facilities

1B

Persons aged 2–64 years with comorbid conditions

Persons aged 65 years and older without comorbid conditions

Children aged 6–23 months

Pregnant women

1C

Children aged 24–59 months

Health care personnel

Household contacts and out-of-home caregivers of children aged less than 6 months

Tier 2

Household contacts of children and adults at increased risk for influenza-related complications

Healthy persons aged 50–64 years

Tier 3

Persons aged 5–49 years without high-risk conditions

In most vaccine shortfall situations, all three groups in tier 1 can be considered top priority, followed by tiers 2 and 3. It would be necessary to further prioritize risk groups 1A, 1B, and 1C separately only on rare occasions when the supply is extremely limited, Nicole M. Smith, Ph.D., said at the meeting. More information about the use of influenza vaccine and antiviral agents is available at

www.cdc.gov/mmwr/preview/mmwrhtml/rr55e628a1.htm

ATLANTA — The prioritization plan for use of inactivated influenza vaccine in the event of a supply shortage or delay has been updated to reflect the recently designated high-risk status of children aged 24–59 months.

The vote, of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting, must be approved by CDC and published before it becomes official. If approved, the new prioritization scheme will look like this:

Tier 1

1A

Persons aged 65 years and older with comorbid conditions

Residents of long-term care facilities

1B

Persons aged 2–64 years with comorbid conditions

Persons aged 65 years and older without comorbid conditions

Children aged 6–23 months

Pregnant women

1C

Children aged 24–59 months

Health care personnel

Household contacts and out-of-home caregivers of children aged less than 6 months

Tier 2

Household contacts of children and adults at increased risk for influenza-related complications

Healthy persons aged 50–64 years

Tier 3

Persons aged 5–49 years without high-risk conditions

In most vaccine shortfall situations, all three groups in tier 1 can be considered top priority, followed by tiers 2 and 3. It would be necessary to further prioritize risk groups 1A, 1B, and 1C separately only on rare occasions when the supply is extremely limited, Nicole M. Smith, Ph.D., said at the meeting. More information about the use of influenza vaccine and antiviral agents is available at

www.cdc.gov/mmwr/preview/mmwrhtml/rr55e628a1.htm

ATLANTA — Children less than 9 years of age who received just one dose of influenza vaccine the first time they were immunized against influenza still don't require a second dose the following season … at least for now.

That was the vote from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting.

Current recommendations from ACIP and the American Academy of Pediatrics call for previously unvaccinated children aged 6 months to 9 years to receive two doses of inactivated influenza vaccine, administered at least 1 month apart. For the live attenuated influenza vaccine (FluMist), children aged 5–8 years who had not previously received either type of influenza vaccine should receive two doses, separated by 6–10 weeks. If a child received only one dose in the previous year, only one dose is required (MMWR 2006;55[early release]:1–41).

However, published and unpublished data suggesting that children may not be adequately protected without receiving two doses in one season—particularly in the response to influenza B strains—have prompted both the ACIP and the AAP to consider recommending that partially immunized children receive a second dose the following season. But after much discussion, ACIP members ultimately decided to wait until more of the data are published.

The AAP's Committee on Infectious Disease (COID) had been leaning toward recommending a second dose prior to the ACIP meeting. But, given ACIP's decision, the COID also may decide to wait, COID chair Dr. Keith R. Powell, vice president and Noah Miller Chair of Pediatrics at Children's Hospital Medical Center of Akron (Ohio), and professor and chair of pediatrics at Northeastern Ohio Universities, Rootstown, said in an interview.

Dr. Kathleen M. Neuzil, a vaccine researcher from the University of Washington, Seattle, summarized the recent data, which include very limited information on immunogenicity in children under the age of 2 years. Children aged 2–6 years with no detectable hemagglutination inhibition assay antibody levels have lower responses than do children with detectable levels, suggesting that “preexisting immunity or infection matters.” Moreover, historical data suggest antibody responses to influenza B vaccine or infection can be substantially lower, compared with responses following influenza A vaccine or infection, she said.

In a published study from Dr. Neu- zil's group, giving 6- to 23-month-old children one dose of influenza vaccine in the spring and another the following autumn was not inferior to giving both doses during flu season. But that study was conducted in the 2002–2003 and 2003–2004 seasons, when the three antigens in the vaccine didn't change (Pediatrics 2005;115:1039–47).

Several yet-unpublished studies conducted during the 2004–2005 season—when two of the antigens differed from the previous season's vaccine—have yielded different results.

In two of those studies, also done in 6- to 23-month-olds who received the first dose in either the spring or the fall, response to the second dose differed by antigen. In 2003–2004, one of the strains was A/Panama/2007/99 (H3N2). In 2004–2005, the H3N2 strain had “drifted” to A/Wyoming/03/2003. Although the children who had been “primed” with the 2003–2004 vaccine had a less robust response to the H3N2 component than did those who received two doses of the identical vaccine, about 70% still had protective antibody levels in one of the studies, while priming had no impact on the H3N2 response in the other study.

In contrast, response to the B strain, which was completely different between the two seasons (B/HongKong/1434/2002 in 2003–2004 vs. B/Jiagsu/10/2003 in 2004–2005), was dramatically lower among those who received just one compared with two identical vaccine doses, in both studies.

A prospective, open-label study comparing one dose with two doses in the fall in vaccine-naive 5- to 8-year-olds yielded similar results: Two doses in the same season were better than one, and preexisting antibody was the strongest predictor of antibody response after one dose. In this study, one-third of the children did not achieve “protective” responses to the B antigen, even after two doses. However, other data suggest that results may differ greatly depending upon how the antibody response to B is measured, Dr. Neuzil remarked.

In a fourth unpublished study of children aged 6–21 months, giving two vaccine doses in the same year was 82% effective in preventing influenzalike illness, compared with 62% with two vaccines given in different years.

ACIP member Dr. Ban Mishu Allos summed up the committee's view prior to its vote: “We have a lot of data that haven't been published yet. We need to look at them further. … Given all that, I'm not in favor of changing.”

Dr. Michael Decker of Fluzone manufacturer Sanofi Pasteur said ideally the recommendation should change every year: One dose would be needed if the vaccine strains are similar to those of the previous year, two doses if they aren't, though such a proposal “is probably unfeasible.”

ATLANTA — Children less than 9 years of age who received just one dose of influenza vaccine the first time they were immunized against influenza still don't require a second dose the following season … at least for now.

That was the vote from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting.

Current recommendations from ACIP and the American Academy of Pediatrics call for previously unvaccinated children aged 6 months to 9 years to receive two doses of inactivated influenza vaccine, administered at least 1 month apart. For the live attenuated influenza vaccine (FluMist), children aged 5–8 years who had not previously received either type of influenza vaccine should receive two doses, separated by 6–10 weeks. If a child received only one dose in the previous year, only one dose is required (MMWR 2006;55[early release]:1–41).

However, published and unpublished data suggesting that children may not be adequately protected without receiving two doses in one season—particularly in the response to influenza B strains—have prompted both the ACIP and the AAP to consider recommending that partially immunized children receive a second dose the following season. But after much discussion, ACIP members ultimately decided to wait until more of the data are published.

The AAP's Committee on Infectious Disease (COID) had been leaning toward recommending a second dose prior to the ACIP meeting. But, given ACIP's decision, the COID also may decide to wait, COID chair Dr. Keith R. Powell, vice president and Noah Miller Chair of Pediatrics at Children's Hospital Medical Center of Akron (Ohio), and professor and chair of pediatrics at Northeastern Ohio Universities, Rootstown, said in an interview.

Dr. Kathleen M. Neuzil, a vaccine researcher from the University of Washington, Seattle, summarized the recent data, which include very limited information on immunogenicity in children under the age of 2 years. Children aged 2–6 years with no detectable hemagglutination inhibition assay antibody levels have lower responses than do children with detectable levels, suggesting that “preexisting immunity or infection matters.” Moreover, historical data suggest antibody responses to influenza B vaccine or infection can be substantially lower, compared with responses following influenza A vaccine or infection, she said.

In a published study from Dr. Neu- zil's group, giving 6- to 23-month-old children one dose of influenza vaccine in the spring and another the following autumn was not inferior to giving both doses during flu season. But that study was conducted in the 2002–2003 and 2003–2004 seasons, when the three antigens in the vaccine didn't change (Pediatrics 2005;115:1039–47).

Several yet-unpublished studies conducted during the 2004–2005 season—when two of the antigens differed from the previous season's vaccine—have yielded different results.

In two of those studies, also done in 6- to 23-month-olds who received the first dose in either the spring or the fall, response to the second dose differed by antigen. In 2003–2004, one of the strains was A/Panama/2007/99 (H3N2). In 2004–2005, the H3N2 strain had “drifted” to A/Wyoming/03/2003. Although the children who had been “primed” with the 2003–2004 vaccine had a less robust response to the H3N2 component than did those who received two doses of the identical vaccine, about 70% still had protective antibody levels in one of the studies, while priming had no impact on the H3N2 response in the other study.

In contrast, response to the B strain, which was completely different between the two seasons (B/HongKong/1434/2002 in 2003–2004 vs. B/Jiagsu/10/2003 in 2004–2005), was dramatically lower among those who received just one compared with two identical vaccine doses, in both studies.

A prospective, open-label study comparing one dose with two doses in the fall in vaccine-naive 5- to 8-year-olds yielded similar results: Two doses in the same season were better than one, and preexisting antibody was the strongest predictor of antibody response after one dose. In this study, one-third of the children did not achieve “protective” responses to the B antigen, even after two doses. However, other data suggest that results may differ greatly depending upon how the antibody response to B is measured, Dr. Neuzil remarked.

In a fourth unpublished study of children aged 6–21 months, giving two vaccine doses in the same year was 82% effective in preventing influenzalike illness, compared with 62% with two vaccines given in different years.

ACIP member Dr. Ban Mishu Allos summed up the committee's view prior to its vote: “We have a lot of data that haven't been published yet. We need to look at them further. … Given all that, I'm not in favor of changing.”

Dr. Michael Decker of Fluzone manufacturer Sanofi Pasteur said ideally the recommendation should change every year: One dose would be needed if the vaccine strains are similar to those of the previous year, two doses if they aren't, though such a proposal “is probably unfeasible.”

ATLANTA — Children less than 9 years of age who received just one dose of influenza vaccine the first time they were immunized against influenza still don't require a second dose the following season … at least for now.

That was the vote from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention at its summer meeting.

Current recommendations from ACIP and the American Academy of Pediatrics call for previously unvaccinated children aged 6 months to 9 years to receive two doses of inactivated influenza vaccine, administered at least 1 month apart. For the live attenuated influenza vaccine (FluMist), children aged 5–8 years who had not previously received either type of influenza vaccine should receive two doses, separated by 6–10 weeks. If a child received only one dose in the previous year, only one dose is required (MMWR 2006;55[early release]:1–41).

However, published and unpublished data suggesting that children may not be adequately protected without receiving two doses in one season—particularly in the response to influenza B strains—have prompted both the ACIP and the AAP to consider recommending that partially immunized children receive a second dose the following season. But after much discussion, ACIP members ultimately decided to wait until more of the data are published.

The AAP's Committee on Infectious Disease (COID) had been leaning toward recommending a second dose prior to the ACIP meeting. But, given ACIP's decision, the COID also may decide to wait, COID chair Dr. Keith R. Powell, vice president and Noah Miller Chair of Pediatrics at Children's Hospital Medical Center of Akron (Ohio), and professor and chair of pediatrics at Northeastern Ohio Universities, Rootstown, said in an interview.

Dr. Kathleen M. Neuzil, a vaccine researcher from the University of Washington, Seattle, summarized the recent data, which include very limited information on immunogenicity in children under the age of 2 years. Children aged 2–6 years with no detectable hemagglutination inhibition assay antibody levels have lower responses than do children with detectable levels, suggesting that “preexisting immunity or infection matters.” Moreover, historical data suggest antibody responses to influenza B vaccine or infection can be substantially lower, compared with responses following influenza A vaccine or infection, she said.

In a published study from Dr. Neu- zil's group, giving 6- to 23-month-old children one dose of influenza vaccine in the spring and another the following autumn was not inferior to giving both doses during flu season. But that study was conducted in the 2002–2003 and 2003–2004 seasons, when the three antigens in the vaccine didn't change (Pediatrics 2005;115:1039–47).

Several yet-unpublished studies conducted during the 2004–2005 season—when two of the antigens differed from the previous season's vaccine—have yielded different results.

In two of those studies, also done in 6- to 23-month-olds who received the first dose in either the spring or the fall, response to the second dose differed by antigen. In 2003–2004, one of the strains was A/Panama/2007/99 (H3N2). In 2004–2005, the H3N2 strain had “drifted” to A/Wyoming/03/2003. Although the children who had been “primed” with the 2003–2004 vaccine had a less robust response to the H3N2 component than did those who received two doses of the identical vaccine, about 70% still had protective antibody levels in one of the studies, while priming had no impact on the H3N2 response in the other study.

In contrast, response to the B strain, which was completely different between the two seasons (B/HongKong/1434/2002 in 2003–2004 vs. B/Jiagsu/10/2003 in 2004–2005), was dramatically lower among those who received just one compared with two identical vaccine doses, in both studies.

A prospective, open-label study comparing one dose with two doses in the fall in vaccine-naive 5- to 8-year-olds yielded similar results: Two doses in the same season were better than one, and preexisting antibody was the strongest predictor of antibody response after one dose. In this study, one-third of the children did not achieve “protective” responses to the B antigen, even after two doses. However, other data suggest that results may differ greatly depending upon how the antibody response to B is measured, Dr. Neuzil remarked.

In a fourth unpublished study of children aged 6–21 months, giving two vaccine doses in the same year was 82% effective in preventing influenzalike illness, compared with 62% with two vaccines given in different years.

ACIP member Dr. Ban Mishu Allos summed up the committee's view prior to its vote: “We have a lot of data that haven't been published yet. We need to look at them further. … Given all that, I'm not in favor of changing.”

Dr. Michael Decker of Fluzone manufacturer Sanofi Pasteur said ideally the recommendation should change every year: One dose would be needed if the vaccine strains are similar to those of the previous year, two doses if they aren't, though such a proposal “is probably unfeasible.”

WASHINGTON — Renal insufficiency in the absence of elevated urinary albumin excretion can occur in patients with type 1 diabetes and may be associated with elevated urinary levels of some inflammatory markers in patients with type 2 diabetes, Dr. Mark E. Molitch and Dr. Monika Niewczas said in separate presentations at the annual scientific sessions of the American Diabetes Association.

Although it was once thought that urinary albumin excretion levels always rose before the decline in glomerular filtration rate (GFR) in patients who went on to develop diabetic nephropathy, recent studies have shown that a significant proportion of diabetic patients have renal insufficiency even in the absence of elevated urinary protein. In one analysis of data from the Third National Health and Nutrition Examination Survey, 30% of 171 adults older than 40 years with type 2 diabetes had chronic renal insufficiency—defined as a GFR of less than 60 mL/min per 1.73 m

Those authors concluded, and clinical guidelines since have concurred, that all patients with diabetes should have annual assessments of GFR as part of their routine kidney assessment. But few data have been collected in patients with type 1 diabetes, said Dr. Molitch, professor of medicine and director of the endocrinology clinic at Northwestern University, Chicago.

Serum creatinine and urine albumin measurements were analyzed among approximately 1,300 adults with type 1 diabetes who had participated in the landmark Diabetes Control and Complications Trial (DCCT) and are now being followed longitudinally in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Serum creatinine and urine albumin measurements in 4-hour collections are obtained from the subjects every other year, and the GFR is estimated.

The proportion with renal insufficiency (estimated GFR of less than 60) increased steadily with time since DCCT ended and EDIC began, from 1.59% during the first 2 years up to 4.22% at EDIC years 9 and 10. Among those individuals, the proportion with normal albumin excretion rates, defined as less than 30 mg per 24 hours, ranged from 52% during years 1 and 2 to 29% at years 5 and 6, said Dr. Molitch.

Of the 55 patients with renal insufficiency at years 9 and 10, 40% had a normal albumin excretion rate, 22% had microalbuminuria (30–300 mg/24 hours), and 38% had albuminuria (greater than 300 mg/24 hours). As expected, the rate of renal insufficiency rose with increasing albumin excretion. Of the total 172 patients with microalbuminuria at year 9 and 10, 7% had estimated GFR less than 60, rising to 30.4% of those with albuminuria.

Dr. Niewczas of the Joslin Diabetes Center, Boston, reported that of a total of 5,627 patients with type 2 diabetes seen at her institution, 64% had normoalbuminuria. Of those 3,623 patients, 11% (398) had an estimated GFR less than 60. That proportion increased to 21% of the 1,542 with microalbuminuria and 58% of the 462 with albuminuria. In the general U.S. population, only about 3% have a GFR less than 60, she noted.

The patients who had renal decline in the absence of an impaired glomerular filtration barrier (no elevated levels of albumin, IgG, or fibronectin) did not differ from the patients with stable renal function with regard to clinical characteristics such as hemoglobin A_1c, systolic blood pressure, or use of antihypertensive medications, she said.

Elevated urinary excretion of the inflammatory markers interleukin-8 and monocyte chemotactic protein 1 were associated with declining renal function in patients with normoalbuminuria, microalbuminuria, and proteinuria, whereas levels of interleukin-6, interferon-inducible protein 10, and regulated upon activation, normal T cell expressed and secreted were not.

Patients who had renal decline without impaired GFR did not differ from those with stable renal function. DR. NIEWCZAS

WASHINGTON — Renal insufficiency in the absence of elevated urinary albumin excretion can occur in patients with type 1 diabetes and may be associated with elevated urinary levels of some inflammatory markers in patients with type 2 diabetes, Dr. Mark E. Molitch and Dr. Monika Niewczas said in separate presentations at the annual scientific sessions of the American Diabetes Association.

Although it was once thought that urinary albumin excretion levels always rose before the decline in glomerular filtration rate (GFR) in patients who went on to develop diabetic nephropathy, recent studies have shown that a significant proportion of diabetic patients have renal insufficiency even in the absence of elevated urinary protein. In one analysis of data from the Third National Health and Nutrition Examination Survey, 30% of 171 adults older than 40 years with type 2 diabetes had chronic renal insufficiency—defined as a GFR of less than 60 mL/min per 1.73 m

Those authors concluded, and clinical guidelines since have concurred, that all patients with diabetes should have annual assessments of GFR as part of their routine kidney assessment. But few data have been collected in patients with type 1 diabetes, said Dr. Molitch, professor of medicine and director of the endocrinology clinic at Northwestern University, Chicago.

Serum creatinine and urine albumin measurements were analyzed among approximately 1,300 adults with type 1 diabetes who had participated in the landmark Diabetes Control and Complications Trial (DCCT) and are now being followed longitudinally in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Serum creatinine and urine albumin measurements in 4-hour collections are obtained from the subjects every other year, and the GFR is estimated.

The proportion with renal insufficiency (estimated GFR of less than 60) increased steadily with time since DCCT ended and EDIC began, from 1.59% during the first 2 years up to 4.22% at EDIC years 9 and 10. Among those individuals, the proportion with normal albumin excretion rates, defined as less than 30 mg per 24 hours, ranged from 52% during years 1 and 2 to 29% at years 5 and 6, said Dr. Molitch.

Of the 55 patients with renal insufficiency at years 9 and 10, 40% had a normal albumin excretion rate, 22% had microalbuminuria (30–300 mg/24 hours), and 38% had albuminuria (greater than 300 mg/24 hours). As expected, the rate of renal insufficiency rose with increasing albumin excretion. Of the total 172 patients with microalbuminuria at year 9 and 10, 7% had estimated GFR less than 60, rising to 30.4% of those with albuminuria.

Dr. Niewczas of the Joslin Diabetes Center, Boston, reported that of a total of 5,627 patients with type 2 diabetes seen at her institution, 64% had normoalbuminuria. Of those 3,623 patients, 11% (398) had an estimated GFR less than 60. That proportion increased to 21% of the 1,542 with microalbuminuria and 58% of the 462 with albuminuria. In the general U.S. population, only about 3% have a GFR less than 60, she noted.

The patients who had renal decline in the absence of an impaired glomerular filtration barrier (no elevated levels of albumin, IgG, or fibronectin) did not differ from the patients with stable renal function with regard to clinical characteristics such as hemoglobin A_1c, systolic blood pressure, or use of antihypertensive medications, she said.

Elevated urinary excretion of the inflammatory markers interleukin-8 and monocyte chemotactic protein 1 were associated with declining renal function in patients with normoalbuminuria, microalbuminuria, and proteinuria, whereas levels of interleukin-6, interferon-inducible protein 10, and regulated upon activation, normal T cell expressed and secreted were not.

Patients who had renal decline without impaired GFR did not differ from those with stable renal function. DR. NIEWCZAS

WASHINGTON — Renal insufficiency in the absence of elevated urinary albumin excretion can occur in patients with type 1 diabetes and may be associated with elevated urinary levels of some inflammatory markers in patients with type 2 diabetes, Dr. Mark E. Molitch and Dr. Monika Niewczas said in separate presentations at the annual scientific sessions of the American Diabetes Association.

Although it was once thought that urinary albumin excretion levels always rose before the decline in glomerular filtration rate (GFR) in patients who went on to develop diabetic nephropathy, recent studies have shown that a significant proportion of diabetic patients have renal insufficiency even in the absence of elevated urinary protein. In one analysis of data from the Third National Health and Nutrition Examination Survey, 30% of 171 adults older than 40 years with type 2 diabetes had chronic renal insufficiency—defined as a GFR of less than 60 mL/min per 1.73 m

Those authors concluded, and clinical guidelines since have concurred, that all patients with diabetes should have annual assessments of GFR as part of their routine kidney assessment. But few data have been collected in patients with type 1 diabetes, said Dr. Molitch, professor of medicine and director of the endocrinology clinic at Northwestern University, Chicago.

Serum creatinine and urine albumin measurements were analyzed among approximately 1,300 adults with type 1 diabetes who had participated in the landmark Diabetes Control and Complications Trial (DCCT) and are now being followed longitudinally in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Serum creatinine and urine albumin measurements in 4-hour collections are obtained from the subjects every other year, and the GFR is estimated.

The proportion with renal insufficiency (estimated GFR of less than 60) increased steadily with time since DCCT ended and EDIC began, from 1.59% during the first 2 years up to 4.22% at EDIC years 9 and 10. Among those individuals, the proportion with normal albumin excretion rates, defined as less than 30 mg per 24 hours, ranged from 52% during years 1 and 2 to 29% at years 5 and 6, said Dr. Molitch.

Of the 55 patients with renal insufficiency at years 9 and 10, 40% had a normal albumin excretion rate, 22% had microalbuminuria (30–300 mg/24 hours), and 38% had albuminuria (greater than 300 mg/24 hours). As expected, the rate of renal insufficiency rose with increasing albumin excretion. Of the total 172 patients with microalbuminuria at year 9 and 10, 7% had estimated GFR less than 60, rising to 30.4% of those with albuminuria.

Dr. Niewczas of the Joslin Diabetes Center, Boston, reported that of a total of 5,627 patients with type 2 diabetes seen at her institution, 64% had normoalbuminuria. Of those 3,623 patients, 11% (398) had an estimated GFR less than 60. That proportion increased to 21% of the 1,542 with microalbuminuria and 58% of the 462 with albuminuria. In the general U.S. population, only about 3% have a GFR less than 60, she noted.

The patients who had renal decline in the absence of an impaired glomerular filtration barrier (no elevated levels of albumin, IgG, or fibronectin) did not differ from the patients with stable renal function with regard to clinical characteristics such as hemoglobin A_1c, systolic blood pressure, or use of antihypertensive medications, she said.

Elevated urinary excretion of the inflammatory markers interleukin-8 and monocyte chemotactic protein 1 were associated with declining renal function in patients with normoalbuminuria, microalbuminuria, and proteinuria, whereas levels of interleukin-6, interferon-inducible protein 10, and regulated upon activation, normal T cell expressed and secreted were not.

Patients who had renal decline without impaired GFR did not differ from those with stable renal function. DR. NIEWCZAS

WASHINGTON — Colesevelam (WelChol), approved in the United States since 2000 for lowering lipid levels, also appears to reduce postprandial glucose in patients with type 2 diabetes, Dr. Franklin Zieve and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

The incidental observation prompted Daiichi Sankyo Inc. to sponsor a prospective study of the glucose-lowering effects of its bile acid sequestrant drug, Dr. Zieve of the Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va., told this newspaper at the meeting.

A total of 65 patients with type 2 diabetes with hemoglobin A_1c levels of 7.0% or above were randomized to receive 3.75 g/day of colesevelam (6 tablets/day) or placebo for 12 weeks, following a 4-week placebo run-in period. Patients continued taking their existing antidiabetic medications. Thirty-two colesevelam and 27 placebo subjects completed the trial.

At 12 weeks, mean postprandial glucose levels were reduced by a significant 18 mg/dL (from 269 to 251) in the colesevelam group, compared with an insignificant gain of 3 mg/dL (285 to 288) in the placebo group. Hemoglobin A_1c levels dropped by approximately 0.3 percentage points from baseline with colesevelam, resulting in a 0.5 percentage-point difference from placebo at 12 weeks.

WASHINGTON — Colesevelam (WelChol), approved in the United States since 2000 for lowering lipid levels, also appears to reduce postprandial glucose in patients with type 2 diabetes, Dr. Franklin Zieve and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

The incidental observation prompted Daiichi Sankyo Inc. to sponsor a prospective study of the glucose-lowering effects of its bile acid sequestrant drug, Dr. Zieve of the Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va., told this newspaper at the meeting.

A total of 65 patients with type 2 diabetes with hemoglobin A_1c levels of 7.0% or above were randomized to receive 3.75 g/day of colesevelam (6 tablets/day) or placebo for 12 weeks, following a 4-week placebo run-in period. Patients continued taking their existing antidiabetic medications. Thirty-two colesevelam and 27 placebo subjects completed the trial.

At 12 weeks, mean postprandial glucose levels were reduced by a significant 18 mg/dL (from 269 to 251) in the colesevelam group, compared with an insignificant gain of 3 mg/dL (285 to 288) in the placebo group. Hemoglobin A_1c levels dropped by approximately 0.3 percentage points from baseline with colesevelam, resulting in a 0.5 percentage-point difference from placebo at 12 weeks.

WASHINGTON — Colesevelam (WelChol), approved in the United States since 2000 for lowering lipid levels, also appears to reduce postprandial glucose in patients with type 2 diabetes, Dr. Franklin Zieve and his associates reported in a poster at the annual scientific sessions of the American Diabetes Association.

The incidental observation prompted Daiichi Sankyo Inc. to sponsor a prospective study of the glucose-lowering effects of its bile acid sequestrant drug, Dr. Zieve of the Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va., told this newspaper at the meeting.

A total of 65 patients with type 2 diabetes with hemoglobin A_1c levels of 7.0% or above were randomized to receive 3.75 g/day of colesevelam (6 tablets/day) or placebo for 12 weeks, following a 4-week placebo run-in period. Patients continued taking their existing antidiabetic medications. Thirty-two colesevelam and 27 placebo subjects completed the trial.

At 12 weeks, mean postprandial glucose levels were reduced by a significant 18 mg/dL (from 269 to 251) in the colesevelam group, compared with an insignificant gain of 3 mg/dL (285 to 288) in the placebo group. Hemoglobin A_1c levels dropped by approximately 0.3 percentage points from baseline with colesevelam, resulting in a 0.5 percentage-point difference from placebo at 12 weeks.

WASHINGTON — Exenatide appears beneficial as adjunctive therapy in patients with type 2 diabetes who have not achieved target glucose levels with a thiazolidinedione alone or in combination with metformin, Dr. Bernard Zinman reported at the annual scientific sessions of the American Diabetes Association.

The incretin mimetic exenatide (Byetta) is currently approved for use in combination with metformin, with or without a sulfonylurea.

Exenatide works by several mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, and improvement in beta-cell function. Thiazolidinediones (TZDs), on the other hand, work primarily by reducing peripheral insulin resistance.

“Given the pathophysiology of type 2 diabetes and the actions of exenatide and [TZDs], this combination therapy may be especially useful in long-term management,” said Dr. Zinman, who is professor of medicine and holds the Sam and Judy Pencer Chair in Diabetes at the University of Toronto.

In a placebo-controlled, double-blind trial involving 233 patients with hemoglobin A_1c levels of 7.1%–10% despite use of a TZD alone (20%) or a TZD plus metformin (80%), 121 were randomized to receive two daily injections of exenatide for 16 weeks (5-mg doses in the first 4 weeks, 10 mg thereafter), while the other 112 received placebo injections. The study was conducted in 49 centers, including 37 in the United States, 7 in Spain, and 5 in Canada.

Of 35 patients from the exenatide group who withdrew prior to the end of the study, 19 (15.7% of the whole exenatide group) did so because of adverse events, compared with 2 of 16 controls (1.8% of the whole control group) who withdrew. Nausea was the most common adverse event, occurring overall in 40% of the exenatide group versus 15% of the placebo group and resulting in withdrawal in 9% and 2%, respectively.

Mean baseline hemoglobin A_1c was 7.9% in both groups. In the intent-to-treat analysis at week 16, mean A_1c had dropped significantly to 7.1%, in the exenatide group, while rising slightly to 8.0% in the placebo group. Reductions in A_1c with exenatide were similar between the patients combining it with TZD and those taking it with both a TZD and metformin, he said.

Among the 86 exenatide and 96 placebo patients who completed the study, 62% of the exenatide group achieved the American Diabetes Association's A_1c target of 7% or less, compared with 16% of the placebo group. The proportions achieving the American Association of Clinical Endocrinologists' target of 6.5% or less were 30% versus 8%, respectively. Both differences were significant.

Seven-point self-monitored glucose values, done at baseline and at the end of the study, showed that patients taking exenatide had significantly lower fasting glucose levels and postprandial glucose excursions at the end of the study compared with baseline.

The mean postprandial drop was 27 mg/dL, and was greatest after breakfast and dinner (mean drop of 34 mg/dL for both meals). The placebo group, in contrast, showed essentially no differences in those measures from baseline to the end of the study, Dr. Zinman reported.

Mean body weight in the exenatide group dropped by 1.54 kg over the 16 weeks, compared with an insignificant 0.2-kg loss with placebo. Patients with the greatest decreases in A_1c also lost the most weight, although even those who didn't lose weight still had significantly better A_1c values, he noted.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Exenatide appears beneficial as adjunctive therapy in patients with type 2 diabetes who have not achieved target glucose levels with a thiazolidinedione alone or in combination with metformin, Dr. Bernard Zinman reported at the annual scientific sessions of the American Diabetes Association.

The incretin mimetic exenatide (Byetta) is currently approved for use in combination with metformin, with or without a sulfonylurea.

Exenatide works by several mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, and improvement in beta-cell function. Thiazolidinediones (TZDs), on the other hand, work primarily by reducing peripheral insulin resistance.

“Given the pathophysiology of type 2 diabetes and the actions of exenatide and [TZDs], this combination therapy may be especially useful in long-term management,” said Dr. Zinman, who is professor of medicine and holds the Sam and Judy Pencer Chair in Diabetes at the University of Toronto.

In a placebo-controlled, double-blind trial involving 233 patients with hemoglobin A_1c levels of 7.1%–10% despite use of a TZD alone (20%) or a TZD plus metformin (80%), 121 were randomized to receive two daily injections of exenatide for 16 weeks (5-mg doses in the first 4 weeks, 10 mg thereafter), while the other 112 received placebo injections. The study was conducted in 49 centers, including 37 in the United States, 7 in Spain, and 5 in Canada.

Of 35 patients from the exenatide group who withdrew prior to the end of the study, 19 (15.7% of the whole exenatide group) did so because of adverse events, compared with 2 of 16 controls (1.8% of the whole control group) who withdrew. Nausea was the most common adverse event, occurring overall in 40% of the exenatide group versus 15% of the placebo group and resulting in withdrawal in 9% and 2%, respectively.

Mean baseline hemoglobin A_1c was 7.9% in both groups. In the intent-to-treat analysis at week 16, mean A_1c had dropped significantly to 7.1%, in the exenatide group, while rising slightly to 8.0% in the placebo group. Reductions in A_1c with exenatide were similar between the patients combining it with TZD and those taking it with both a TZD and metformin, he said.

Among the 86 exenatide and 96 placebo patients who completed the study, 62% of the exenatide group achieved the American Diabetes Association's A_1c target of 7% or less, compared with 16% of the placebo group. The proportions achieving the American Association of Clinical Endocrinologists' target of 6.5% or less were 30% versus 8%, respectively. Both differences were significant.

Seven-point self-monitored glucose values, done at baseline and at the end of the study, showed that patients taking exenatide had significantly lower fasting glucose levels and postprandial glucose excursions at the end of the study compared with baseline.

The mean postprandial drop was 27 mg/dL, and was greatest after breakfast and dinner (mean drop of 34 mg/dL for both meals). The placebo group, in contrast, showed essentially no differences in those measures from baseline to the end of the study, Dr. Zinman reported.

Mean body weight in the exenatide group dropped by 1.54 kg over the 16 weeks, compared with an insignificant 0.2-kg loss with placebo. Patients with the greatest decreases in A_1c also lost the most weight, although even those who didn't lose weight still had significantly better A_1c values, he noted.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Exenatide appears beneficial as adjunctive therapy in patients with type 2 diabetes who have not achieved target glucose levels with a thiazolidinedione alone or in combination with metformin, Dr. Bernard Zinman reported at the annual scientific sessions of the American Diabetes Association.

The incretin mimetic exenatide (Byetta) is currently approved for use in combination with metformin, with or without a sulfonylurea.

Exenatide works by several mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, and improvement in beta-cell function. Thiazolidinediones (TZDs), on the other hand, work primarily by reducing peripheral insulin resistance.

“Given the pathophysiology of type 2 diabetes and the actions of exenatide and [TZDs], this combination therapy may be especially useful in long-term management,” said Dr. Zinman, who is professor of medicine and holds the Sam and Judy Pencer Chair in Diabetes at the University of Toronto.

In a placebo-controlled, double-blind trial involving 233 patients with hemoglobin A_1c levels of 7.1%–10% despite use of a TZD alone (20%) or a TZD plus metformin (80%), 121 were randomized to receive two daily injections of exenatide for 16 weeks (5-mg doses in the first 4 weeks, 10 mg thereafter), while the other 112 received placebo injections. The study was conducted in 49 centers, including 37 in the United States, 7 in Spain, and 5 in Canada.

Of 35 patients from the exenatide group who withdrew prior to the end of the study, 19 (15.7% of the whole exenatide group) did so because of adverse events, compared with 2 of 16 controls (1.8% of the whole control group) who withdrew. Nausea was the most common adverse event, occurring overall in 40% of the exenatide group versus 15% of the placebo group and resulting in withdrawal in 9% and 2%, respectively.

Mean baseline hemoglobin A_1c was 7.9% in both groups. In the intent-to-treat analysis at week 16, mean A_1c had dropped significantly to 7.1%, in the exenatide group, while rising slightly to 8.0% in the placebo group. Reductions in A_1c with exenatide were similar between the patients combining it with TZD and those taking it with both a TZD and metformin, he said.

Among the 86 exenatide and 96 placebo patients who completed the study, 62% of the exenatide group achieved the American Diabetes Association's A_1c target of 7% or less, compared with 16% of the placebo group. The proportions achieving the American Association of Clinical Endocrinologists' target of 6.5% or less were 30% versus 8%, respectively. Both differences were significant.

Seven-point self-monitored glucose values, done at baseline and at the end of the study, showed that patients taking exenatide had significantly lower fasting glucose levels and postprandial glucose excursions at the end of the study compared with baseline.

The mean postprandial drop was 27 mg/dL, and was greatest after breakfast and dinner (mean drop of 34 mg/dL for both meals). The placebo group, in contrast, showed essentially no differences in those measures from baseline to the end of the study, Dr. Zinman reported.

Mean body weight in the exenatide group dropped by 1.54 kg over the 16 weeks, compared with an insignificant 0.2-kg loss with placebo. Patients with the greatest decreases in A_1c also lost the most weight, although even those who didn't lose weight still had significantly better A_1c values, he noted.

ELSEVIER GLOBAL MEDICAL NEWS

Valproate poses by far the greatest teratogenic risk of all the commonly prescribed antiepileptic drugs, according to Dr. Kimford J. Meador of the University of Florida, Gainesville, and his associates in the Neurodevelopmental Effects of Antiepileptic Drugs Study Group.

“We advise that [valproate] not be used as the AED of first choice for women of childbearing potential, and, when used, its dose should be limited, if possible,” the group wrote (Neurology 2006;67:407–12).

Current guidelines from the American Academy of Neurology advise a variety of ways to minimize the risk of teratogenicity with AEDs, including use of monotherapy if possible, use of the lowest effective dose, supplementation with folate, and treatment of the infant with vitamin K at birth (Neurology 1998;51:944–8). However, no current recommendation addresses the differential teratogenetic risk associated with individual AEDs, Dr. Meador and his associates noted.

The data come from an ongoing prospective observational study of mother/child pairs across 25 epilepsy centers in the United States and United Kingdom. A total of 323 mothers and 333 children were available for analysis. Mean gestational ages at the time of enrollment were 17 weeks for the 69 infants exposed to valproate, 18 weeks for the 98 lamotrigine-exposed infants, and 19 weeks for both the 110 whose mothers who used carbamazepine and for the 56 infants exposed to phenytoin. Mean age of the children at the time of analysis ranged from 2.7 years with lamotrigine to 3.5 years for valproate and carbamazepine.

Major congenital malformation or fetal death occurred in 20.3% with valproate, 10.7% with phenytoin, 8.2% carbamazepine, and 1.02% with lamotrigine. Not only was the valproate risk approximately twice that of the other AEDs, but valproate was the only one to show a dose-response relationship: The mean valproate dose for the pregnancies with serious adverse fetal outcomes was 1,268 mg/day compared with just 844 mg/day for those without serious adverse outcomes.

The differences in risk between the AEDs were accounted for by congenital malformation rather than death. Indeed, death rates were actually slightly higher for both carbamazepine and phenytoin (3.6%) than for valproate (2.9%). There were no deaths with lamotrigine. Congenital malformations, on the other hand, occurred in 17.4% with valproate compared with 7.1% with phenytoin, 4.5% carbamazepine, and 1.0% lamotrigine.

Clinicians are urged to encourage their pregnant patients on AEDs to join one of the pregnancy registries around the world that are seeking additional information on AED risk for anatomic teratogenesis. The North American Pregnancy Registry has a toll-free number, 1-888-AED-AED4. The EURAP registry, covering Europe and elsewhere, is online at www.eurapinternational.org

Valproate poses by far the greatest teratogenic risk of all the commonly prescribed antiepileptic drugs, according to Dr. Kimford J. Meador of the University of Florida, Gainesville, and his associates in the Neurodevelopmental Effects of Antiepileptic Drugs Study Group.

“We advise that [valproate] not be used as the AED of first choice for women of childbearing potential, and, when used, its dose should be limited, if possible,” the group wrote (Neurology 2006;67:407–12).

Current guidelines from the American Academy of Neurology advise a variety of ways to minimize the risk of teratogenicity with AEDs, including use of monotherapy if possible, use of the lowest effective dose, supplementation with folate, and treatment of the infant with vitamin K at birth (Neurology 1998;51:944–8). However, no current recommendation addresses the differential teratogenetic risk associated with individual AEDs, Dr. Meador and his associates noted.

The data come from an ongoing prospective observational study of mother/child pairs across 25 epilepsy centers in the United States and United Kingdom. A total of 323 mothers and 333 children were available for analysis. Mean gestational ages at the time of enrollment were 17 weeks for the 69 infants exposed to valproate, 18 weeks for the 98 lamotrigine-exposed infants, and 19 weeks for both the 110 whose mothers who used carbamazepine and for the 56 infants exposed to phenytoin. Mean age of the children at the time of analysis ranged from 2.7 years with lamotrigine to 3.5 years for valproate and carbamazepine.

Major congenital malformation or fetal death occurred in 20.3% with valproate, 10.7% with phenytoin, 8.2% carbamazepine, and 1.02% with lamotrigine. Not only was the valproate risk approximately twice that of the other AEDs, but valproate was the only one to show a dose-response relationship: The mean valproate dose for the pregnancies with serious adverse fetal outcomes was 1,268 mg/day compared with just 844 mg/day for those without serious adverse outcomes.

The differences in risk between the AEDs were accounted for by congenital malformation rather than death. Indeed, death rates were actually slightly higher for both carbamazepine and phenytoin (3.6%) than for valproate (2.9%). There were no deaths with lamotrigine. Congenital malformations, on the other hand, occurred in 17.4% with valproate compared with 7.1% with phenytoin, 4.5% carbamazepine, and 1.0% lamotrigine.

Clinicians are urged to encourage their pregnant patients on AEDs to join one of the pregnancy registries around the world that are seeking additional information on AED risk for anatomic teratogenesis. The North American Pregnancy Registry has a toll-free number, 1-888-AED-AED4. The EURAP registry, covering Europe and elsewhere, is online at www.eurapinternational.org

Valproate poses by far the greatest teratogenic risk of all the commonly prescribed antiepileptic drugs, according to Dr. Kimford J. Meador of the University of Florida, Gainesville, and his associates in the Neurodevelopmental Effects of Antiepileptic Drugs Study Group.

“We advise that [valproate] not be used as the AED of first choice for women of childbearing potential, and, when used, its dose should be limited, if possible,” the group wrote (Neurology 2006;67:407–12).

Current guidelines from the American Academy of Neurology advise a variety of ways to minimize the risk of teratogenicity with AEDs, including use of monotherapy if possible, use of the lowest effective dose, supplementation with folate, and treatment of the infant with vitamin K at birth (Neurology 1998;51:944–8). However, no current recommendation addresses the differential teratogenetic risk associated with individual AEDs, Dr. Meador and his associates noted.

The data come from an ongoing prospective observational study of mother/child pairs across 25 epilepsy centers in the United States and United Kingdom. A total of 323 mothers and 333 children were available for analysis. Mean gestational ages at the time of enrollment were 17 weeks for the 69 infants exposed to valproate, 18 weeks for the 98 lamotrigine-exposed infants, and 19 weeks for both the 110 whose mothers who used carbamazepine and for the 56 infants exposed to phenytoin. Mean age of the children at the time of analysis ranged from 2.7 years with lamotrigine to 3.5 years for valproate and carbamazepine.

Major congenital malformation or fetal death occurred in 20.3% with valproate, 10.7% with phenytoin, 8.2% carbamazepine, and 1.02% with lamotrigine. Not only was the valproate risk approximately twice that of the other AEDs, but valproate was the only one to show a dose-response relationship: The mean valproate dose for the pregnancies with serious adverse fetal outcomes was 1,268 mg/day compared with just 844 mg/day for those without serious adverse outcomes.

The differences in risk between the AEDs were accounted for by congenital malformation rather than death. Indeed, death rates were actually slightly higher for both carbamazepine and phenytoin (3.6%) than for valproate (2.9%). There were no deaths with lamotrigine. Congenital malformations, on the other hand, occurred in 17.4% with valproate compared with 7.1% with phenytoin, 4.5% carbamazepine, and 1.0% lamotrigine.

Clinicians are urged to encourage their pregnant patients on AEDs to join one of the pregnancy registries around the world that are seeking additional information on AED risk for anatomic teratogenesis. The North American Pregnancy Registry has a toll-free number, 1-888-AED-AED4. The EURAP registry, covering Europe and elsewhere, is online at www.eurapinternational.org

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease cause by Neisseria meningitis serogroups A, C, Y, and W-135.

In May 2005, the CDC published ACIP's recommendation for routine use of the vaccine in 11–12 year olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

Following the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11–12 year olds, but for continuation of immunization in the other recommended groups.

The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person who will be traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply. (MMWR 2006;55:567–8).

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease cause by Neisseria meningitis serogroups A, C, Y, and W-135.

In May 2005, the CDC published ACIP's recommendation for routine use of the vaccine in 11–12 year olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

Following the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11–12 year olds, but for continuation of immunization in the other recommended groups.

The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person who will be traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply. (MMWR 2006;55:567–8).

ATLANTA — The Centers for Disease Control and Prevention is monitoring the shortage of tetravalent meningococcal conjugate vaccine on a biweekly basis and will announce a return to routine recommendations when the supply and demand situation improves, Dr. Gregory S. Wallace, of the CDC, told the Advisory Committee on Immunization Practices at its June meeting.

Availability of Sanofi Pasteur's Menactra vaccine will likely be limited through the fall of 2006, according to a statement from the Food and Drug Administration.

Licensed in January 2005, Menactra is indicated for active immunization of individuals aged 11–55 years against invasive meningococcal disease cause by Neisseria meningitis serogroups A, C, Y, and W-135.

In May 2005, the CDC published ACIP's recommendation for routine use of the vaccine in 11–12 year olds, for high school entry in those previously unvaccinated, and for high-risk groups including college freshmen living in dormitories (MMWR 2005;54:1–21).

Following the announcement of a supply problem earlier this year, the CDC published interim guidelines calling for the deferral of routine vaccination in 11–12 year olds, but for continuation of immunization in the other recommended groups.

The old tetravalent polysaccharide meningococcal vaccine (Menomune) is an acceptable alternative in certain high-risk situations, such as for a person who will be traveling to an area where meningococcal disease is widely prevalent. However, that vaccine also is in short supply. (MMWR 2006;55:567–8).