Michele G. Sullivan

CHICAGO — A cloudy cervical exudate observed on clinical exam is strongly associated with Mycoplasma genitalium infections, especially among women older than 25 years.

The age correlation suggests a different immunologic response to the bacterium among older women, and may partially explain the conflicting literature regarding the association of M. genitalium and cervicitis, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Dr. Manhart and her associates examined M. genitalium infections among 1,038 women aged 14–46 years who attended a public STD clinic from 2000 to 2006. M. genitalium infection was determined by either polymerase chain reaction or transcription-mediated amplification assay.

M. genitalium was detected in 119 women (11%). Of these, five (4%) were coinfected with gonorrhea and seven (6%) with chlamydia, said Dr. Manhart of the University of Washington, Seattle.

Women with M. genitalium were significantly younger than those without (24 vs. 27 years), and significantly more likely to be black (57% vs. 35%). They had a significantly younger age at sexual debut (15 vs. 16 years), were more likely to be current smokers, and were less likely to be taking oral contraceptives. There were no significant associations with sexual behaviors (other than debut) or with the time since their last sexual encounter.

The incidence of mucopurulent cervicitis was not significantly different between those with and without infection (14% vs. 9%). The incidence of mild cervicitis was also similar between groups. “The majority of women in both groups had very low levels of polymorphonuclear neutrophils (up to 14 per high-magnification field),” Dr. Manhart said.

“However, we did see a significant difference when we looked at the incidence of cloudy cervical discharge. This was present in 22% of the women with M. genitalium infections, but only in 12% of those without the infection,” she said.

This pattern was consistent in a multivariate analysis that adjusted for other known causes of mucopurulent cervicitis and cloudy discharge, including gonorrhea and chlamydia infections and the use of oral contraceptives, Dr. Manhart said.

After adjusting for these factors, women with mucopurulent cervicitis had a modest, but nonsignificant, 60% increased risk of the infection, compared with those without mucopurulent cervicitis. Women with cloudy cervical discharge, however, were twice as likely to have the infection as those without cloudy discharge—a significantly increased risk.

Of eight studies which have examined the association of M. genitalium and cervicitis, four have found a significant association, while four have not, Dr. Manhart said. “The studies that showed an association looked at populations with broad age groups, ranging from 18 years to the mid-40s, while those that showed no relationship were conducted in adolescent populations or among very young college students.”

The researchers investigated the impact of age on the risk of M. genitalium infection and cervicitis. Although the infection was more prevalent among younger women, they were less likely than older women to show an association between M. genitalium and cervicitis. In women younger than 25 years, there was no significant relationship between the infection and either mucopurulent cervicitis or cloudy discharge. But women older than 25 years who had M. genitalium were 2.5 times more likely to have mucopurulent discharge and 2.4 times more likely to have cloudy cervical discharge than women under 25 years.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women,” Dr. Manhart said. “While we think these results are interesting and intriguing, we really can't draw any conclusions about causality.”

Dr. Manhart reported no financial disclosures related to the study.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women.” DR. MANHART

CHICAGO — A cloudy cervical exudate observed on clinical exam is strongly associated with Mycoplasma genitalium infections, especially among women older than 25 years.

The age correlation suggests a different immunologic response to the bacterium among older women, and may partially explain the conflicting literature regarding the association of M. genitalium and cervicitis, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Dr. Manhart and her associates examined M. genitalium infections among 1,038 women aged 14–46 years who attended a public STD clinic from 2000 to 2006. M. genitalium infection was determined by either polymerase chain reaction or transcription-mediated amplification assay.

M. genitalium was detected in 119 women (11%). Of these, five (4%) were coinfected with gonorrhea and seven (6%) with chlamydia, said Dr. Manhart of the University of Washington, Seattle.

Women with M. genitalium were significantly younger than those without (24 vs. 27 years), and significantly more likely to be black (57% vs. 35%). They had a significantly younger age at sexual debut (15 vs. 16 years), were more likely to be current smokers, and were less likely to be taking oral contraceptives. There were no significant associations with sexual behaviors (other than debut) or with the time since their last sexual encounter.

The incidence of mucopurulent cervicitis was not significantly different between those with and without infection (14% vs. 9%). The incidence of mild cervicitis was also similar between groups. “The majority of women in both groups had very low levels of polymorphonuclear neutrophils (up to 14 per high-magnification field),” Dr. Manhart said.

“However, we did see a significant difference when we looked at the incidence of cloudy cervical discharge. This was present in 22% of the women with M. genitalium infections, but only in 12% of those without the infection,” she said.

This pattern was consistent in a multivariate analysis that adjusted for other known causes of mucopurulent cervicitis and cloudy discharge, including gonorrhea and chlamydia infections and the use of oral contraceptives, Dr. Manhart said.

After adjusting for these factors, women with mucopurulent cervicitis had a modest, but nonsignificant, 60% increased risk of the infection, compared with those without mucopurulent cervicitis. Women with cloudy cervical discharge, however, were twice as likely to have the infection as those without cloudy discharge—a significantly increased risk.

Of eight studies which have examined the association of M. genitalium and cervicitis, four have found a significant association, while four have not, Dr. Manhart said. “The studies that showed an association looked at populations with broad age groups, ranging from 18 years to the mid-40s, while those that showed no relationship were conducted in adolescent populations or among very young college students.”

The researchers investigated the impact of age on the risk of M. genitalium infection and cervicitis. Although the infection was more prevalent among younger women, they were less likely than older women to show an association between M. genitalium and cervicitis. In women younger than 25 years, there was no significant relationship between the infection and either mucopurulent cervicitis or cloudy discharge. But women older than 25 years who had M. genitalium were 2.5 times more likely to have mucopurulent discharge and 2.4 times more likely to have cloudy cervical discharge than women under 25 years.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women,” Dr. Manhart said. “While we think these results are interesting and intriguing, we really can't draw any conclusions about causality.”

Dr. Manhart reported no financial disclosures related to the study.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women.” DR. MANHART

CHICAGO — A cloudy cervical exudate observed on clinical exam is strongly associated with Mycoplasma genitalium infections, especially among women older than 25 years.

The age correlation suggests a different immunologic response to the bacterium among older women, and may partially explain the conflicting literature regarding the association of M. genitalium and cervicitis, Lisa Manhart, Ph.D., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention.

Dr. Manhart and her associates examined M. genitalium infections among 1,038 women aged 14–46 years who attended a public STD clinic from 2000 to 2006. M. genitalium infection was determined by either polymerase chain reaction or transcription-mediated amplification assay.

M. genitalium was detected in 119 women (11%). Of these, five (4%) were coinfected with gonorrhea and seven (6%) with chlamydia, said Dr. Manhart of the University of Washington, Seattle.

Women with M. genitalium were significantly younger than those without (24 vs. 27 years), and significantly more likely to be black (57% vs. 35%). They had a significantly younger age at sexual debut (15 vs. 16 years), were more likely to be current smokers, and were less likely to be taking oral contraceptives. There were no significant associations with sexual behaviors (other than debut) or with the time since their last sexual encounter.

The incidence of mucopurulent cervicitis was not significantly different between those with and without infection (14% vs. 9%). The incidence of mild cervicitis was also similar between groups. “The majority of women in both groups had very low levels of polymorphonuclear neutrophils (up to 14 per high-magnification field),” Dr. Manhart said.

“However, we did see a significant difference when we looked at the incidence of cloudy cervical discharge. This was present in 22% of the women with M. genitalium infections, but only in 12% of those without the infection,” she said.

This pattern was consistent in a multivariate analysis that adjusted for other known causes of mucopurulent cervicitis and cloudy discharge, including gonorrhea and chlamydia infections and the use of oral contraceptives, Dr. Manhart said.

After adjusting for these factors, women with mucopurulent cervicitis had a modest, but nonsignificant, 60% increased risk of the infection, compared with those without mucopurulent cervicitis. Women with cloudy cervical discharge, however, were twice as likely to have the infection as those without cloudy discharge—a significantly increased risk.

Of eight studies which have examined the association of M. genitalium and cervicitis, four have found a significant association, while four have not, Dr. Manhart said. “The studies that showed an association looked at populations with broad age groups, ranging from 18 years to the mid-40s, while those that showed no relationship were conducted in adolescent populations or among very young college students.”

The researchers investigated the impact of age on the risk of M. genitalium infection and cervicitis. Although the infection was more prevalent among younger women, they were less likely than older women to show an association between M. genitalium and cervicitis. In women younger than 25 years, there was no significant relationship between the infection and either mucopurulent cervicitis or cloudy discharge. But women older than 25 years who had M. genitalium were 2.5 times more likely to have mucopurulent discharge and 2.4 times more likely to have cloudy cervical discharge than women under 25 years.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women,” Dr. Manhart said. “While we think these results are interesting and intriguing, we really can't draw any conclusions about causality.”

Dr. Manhart reported no financial disclosures related to the study.

“This suggests that older women have a different immunologic response to M. genitalium than do younger women.” DR. MANHART

CHICAGO — Cancer- and genital wart-associated HPV was the most prevalent sexually transmitted disease among teenage girls, affecting 18% of participants in the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%, said Dr. Sara Forhan, lead author of the population-based study sponsored by the Centers for Disease Control and Prevention.

These infections occur quickly after sexual debut, Dr. Forhan noted. “Of particular importance is how fast these infections appear,” she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection, she said: 50% of teens who reported three or more partners had at least one of the STDs.

The results underscore the importance of HPV vaccination, as well as chlamydia screening, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention. “Today's data demonstrate the significant health risk that STDs pose to millions of young women in this country every year. Given that the health effects of STDs for women—from infertility to cervical cancer—are particularly severe, STD screening, vaccination, and other prevention strategies for sexually active women are among our highest public health priorities.”

Results from a study at another meeting underscored the success of an HPV vaccine being studied right now in terms of risk of cervical cancer.

The survey highlighted sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common sexual infections, compared with 20% of white teens, investigators reported at a press briefing during a CDC-sponsored conference on STD prevention.

“While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection,” Dr. Forhan said.

“For any other disease, we would be calling this an epidemic,” said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention.

“These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs.”

Dr. Forhan of the CDC extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues.

As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted.

But because the survey identified an overall STD rate of 26%, “This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer,” Dr. Forhan said.

At the annual meeting of the Society of Gynecologic Oncologists in Tampa, Dr. Diane Harper reported that the Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of HPV.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and eightfold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

“This is an amazing result that bodes well for women's protection against cervical cancer,” she commented in an interview, explaining that “there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers.”

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18. There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide “a significant possible reduction in disease.”

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honoraria from both companies for consultations and speaking fees.

Sharon Worcester contributed to this article.

Overall, 26% of 14- to 19-year-olds wereinfectedwith at leastone STD. DR. FORHAN

This Month's Talk Back Question

How do you counsel sexually active teens in your practice to prevent sexually transmitted diseases?

CHICAGO — Cancer- and genital wart-associated HPV was the most prevalent sexually transmitted disease among teenage girls, affecting 18% of participants in the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%, said Dr. Sara Forhan, lead author of the population-based study sponsored by the Centers for Disease Control and Prevention.

These infections occur quickly after sexual debut, Dr. Forhan noted. “Of particular importance is how fast these infections appear,” she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection, she said: 50% of teens who reported three or more partners had at least one of the STDs.

The results underscore the importance of HPV vaccination, as well as chlamydia screening, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention. “Today's data demonstrate the significant health risk that STDs pose to millions of young women in this country every year. Given that the health effects of STDs for women—from infertility to cervical cancer—are particularly severe, STD screening, vaccination, and other prevention strategies for sexually active women are among our highest public health priorities.”

Results from a study at another meeting underscored the success of an HPV vaccine being studied right now in terms of risk of cervical cancer.

The survey highlighted sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common sexual infections, compared with 20% of white teens, investigators reported at a press briefing during a CDC-sponsored conference on STD prevention.

“While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection,” Dr. Forhan said.

“For any other disease, we would be calling this an epidemic,” said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention.

“These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs.”

Dr. Forhan of the CDC extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues.

As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted.

But because the survey identified an overall STD rate of 26%, “This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer,” Dr. Forhan said.

At the annual meeting of the Society of Gynecologic Oncologists in Tampa, Dr. Diane Harper reported that the Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of HPV.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and eightfold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

“This is an amazing result that bodes well for women's protection against cervical cancer,” she commented in an interview, explaining that “there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers.”

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18. There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide “a significant possible reduction in disease.”

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honoraria from both companies for consultations and speaking fees.

Sharon Worcester contributed to this article.

Overall, 26% of 14- to 19-year-olds wereinfectedwith at leastone STD. DR. FORHAN

This Month's Talk Back Question

How do you counsel sexually active teens in your practice to prevent sexually transmitted diseases?

CHICAGO — Cancer- and genital wart-associated HPV was the most prevalent sexually transmitted disease among teenage girls, affecting 18% of participants in the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%, said Dr. Sara Forhan, lead author of the population-based study sponsored by the Centers for Disease Control and Prevention.

These infections occur quickly after sexual debut, Dr. Forhan noted. “Of particular importance is how fast these infections appear,” she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection, she said: 50% of teens who reported three or more partners had at least one of the STDs.

The results underscore the importance of HPV vaccination, as well as chlamydia screening, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention. “Today's data demonstrate the significant health risk that STDs pose to millions of young women in this country every year. Given that the health effects of STDs for women—from infertility to cervical cancer—are particularly severe, STD screening, vaccination, and other prevention strategies for sexually active women are among our highest public health priorities.”

Results from a study at another meeting underscored the success of an HPV vaccine being studied right now in terms of risk of cervical cancer.

The survey highlighted sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common sexual infections, compared with 20% of white teens, investigators reported at a press briefing during a CDC-sponsored conference on STD prevention.

“While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection,” Dr. Forhan said.

“For any other disease, we would be calling this an epidemic,” said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention.

“These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs.”

Dr. Forhan of the CDC extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues.

As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present. The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted.

But because the survey identified an overall STD rate of 26%, “This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer,” Dr. Forhan said.

At the annual meeting of the Society of Gynecologic Oncologists in Tampa, Dr. Diane Harper reported that the Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of HPV.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and eightfold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

“This is an amazing result that bodes well for women's protection against cervical cancer,” she commented in an interview, explaining that “there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers.”

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18. There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide “a significant possible reduction in disease.”

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honoraria from both companies for consultations and speaking fees.

Sharon Worcester contributed to this article.

Overall, 26% of 14- to 19-year-olds wereinfectedwith at leastone STD. DR. FORHAN

This Month's Talk Back Question

How do you counsel sexually active teens in your practice to prevent sexually transmitted diseases?

Adolescents who engage in frequent school-based or extracurricular physical activity–especially Rollerblading, skateboarding, and bicycling–are up to 48% less likely to become overweight or obese in early adulthood, Dr. David Menschik and his colleagues reported.

These wheeled sports also helped those who were overweight to slim down as they entered early adulthood, the researchers wrote (Arch. Pediatr. Adolesc. Med. 2008;162:29–33).

“Overweight adolescents who participated [in wheeled activities] three to four times per week were 85% more likely to become normal-weight adults than [were] overweight adolescents not participating,” wrote Dr. Menschik, who was with the preventive medicine residency at Johns Hopkins University, Baltimore, and his coauthors. Dr. Menschik is now at the Food and Drug Administration.

Team sports and swimming also were beneficial to both normal- and overweight teens, but the study did not find a correlation between jogging or walking and achieving a normal adult weight.

The researchers drew their data from 3,345 subjects who were included in the National Longitudinal Study of Adolescent Health.

“In view of an obesity epidemic costing the United States an estimated $117 billion annually, policy makers now have evidence that a relatively low-cost strategy may offer a long-lasting solution,” Dr. Menschik and his colleagues concluded.

Adolescents who engage in frequent school-based or extracurricular physical activity–especially Rollerblading, skateboarding, and bicycling–are up to 48% less likely to become overweight or obese in early adulthood, Dr. David Menschik and his colleagues reported.

These wheeled sports also helped those who were overweight to slim down as they entered early adulthood, the researchers wrote (Arch. Pediatr. Adolesc. Med. 2008;162:29–33).

“Overweight adolescents who participated [in wheeled activities] three to four times per week were 85% more likely to become normal-weight adults than [were] overweight adolescents not participating,” wrote Dr. Menschik, who was with the preventive medicine residency at Johns Hopkins University, Baltimore, and his coauthors. Dr. Menschik is now at the Food and Drug Administration.

Team sports and swimming also were beneficial to both normal- and overweight teens, but the study did not find a correlation between jogging or walking and achieving a normal adult weight.

The researchers drew their data from 3,345 subjects who were included in the National Longitudinal Study of Adolescent Health.

“In view of an obesity epidemic costing the United States an estimated $117 billion annually, policy makers now have evidence that a relatively low-cost strategy may offer a long-lasting solution,” Dr. Menschik and his colleagues concluded.

Adolescents who engage in frequent school-based or extracurricular physical activity–especially Rollerblading, skateboarding, and bicycling–are up to 48% less likely to become overweight or obese in early adulthood, Dr. David Menschik and his colleagues reported.

These wheeled sports also helped those who were overweight to slim down as they entered early adulthood, the researchers wrote (Arch. Pediatr. Adolesc. Med. 2008;162:29–33).

“Overweight adolescents who participated [in wheeled activities] three to four times per week were 85% more likely to become normal-weight adults than [were] overweight adolescents not participating,” wrote Dr. Menschik, who was with the preventive medicine residency at Johns Hopkins University, Baltimore, and his coauthors. Dr. Menschik is now at the Food and Drug Administration.

Team sports and swimming also were beneficial to both normal- and overweight teens, but the study did not find a correlation between jogging or walking and achieving a normal adult weight.

The researchers drew their data from 3,345 subjects who were included in the National Longitudinal Study of Adolescent Health.

“In view of an obesity epidemic costing the United States an estimated $117 billion annually, policy makers now have evidence that a relatively low-cost strategy may offer a long-lasting solution,” Dr. Menschik and his colleagues concluded.

Adolescents who are involved in bullying–either as a victim, bully, or both–are more likely than bystanders to report feelings of low self-worth and sadness and to feel unsafe in their school.

These issues are most troubling in children who are both bullies and victims, Dr. Gwen M. Glew and her colleagues reported. The findings suggest, “that we should be particularly concerned about [these children] because they are much more likely to endorse carrying a gun to school,” the investigators wrote (J. Ped. 2008;152:123–8).

Dr. Glew of the University of Washington, Seattle, and her associates surveyed 5,391 children from a single urban public school district in grades 7, 9, and 11. The students rated how often they bullied and were victims of bullying; their feelings of safety at school; their feelings of self-worth and daily sadness; and their judgments on the high-risk behaviors of bringing a gun to school, fighting, cheating, stealing, smoking, and drinking alcohol.

The researchers also obtained grade point averages for all surveyed students.

Overall, 74% of the students reported being neither a bully nor victim–these “bystanders” were used as the control group. Fifteen percent of students reported being bullied, 7% said they bullied others, and 4% were both bullies and victims.

Only 27% of the victims and 30% of the bully-victims said they had reported their victimization to another person.

Victims were twice as likely feel unsafe at school, sad on most days, and “no good at all,” compared with bystanders, and after controlling for age, gender, ethnicity, and income status. They also were more likely to say that they didn't feel as if they belonged at their school.

Academic performance was significantly associated with being a victim; for every 1-point rise in grade point average, the odds of being a victim dropped by 10%. But victims were not more likely than bystanders to endorse the high-risk behaviors.

Bullies were almost twice as likely to report feeling unsafe at school and sad on most days, compared with bystanders. They were three times as likely to endorse the idea of beating up someone who starts a fight, and twice as likely to say it's OK to pick a fight or to cheat at school.

In addition, the investigators found that bully-victims were 2.5 times more likely to feel unsafe and to report feeling “no good at all” and twice as likely to report daily sadness, compared with bystanders. They also were three times more likely to say it was all right to bring a gun to school and to cheat. “There are many reasons why adolescents might endorse carrying a gun to school,” Dr. Glew and her associates said, noting a 2000 report that found 66% of school shooters reported feeling “bullied, attacked, threatened, or persecuted prior to the incident.”

The investigators' own findings are “consistent with the literature, which suggests that the bully-victim group is the most troubled.”

The study was supported by a grant from the National Institutes of Mental Health; none of the investigators reported a conflict of interest.

Adolescents who are involved in bullying–either as a victim, bully, or both–are more likely than bystanders to report feelings of low self-worth and sadness and to feel unsafe in their school.

These issues are most troubling in children who are both bullies and victims, Dr. Gwen M. Glew and her colleagues reported. The findings suggest, “that we should be particularly concerned about [these children] because they are much more likely to endorse carrying a gun to school,” the investigators wrote (J. Ped. 2008;152:123–8).

Dr. Glew of the University of Washington, Seattle, and her associates surveyed 5,391 children from a single urban public school district in grades 7, 9, and 11. The students rated how often they bullied and were victims of bullying; their feelings of safety at school; their feelings of self-worth and daily sadness; and their judgments on the high-risk behaviors of bringing a gun to school, fighting, cheating, stealing, smoking, and drinking alcohol.

The researchers also obtained grade point averages for all surveyed students.

Overall, 74% of the students reported being neither a bully nor victim–these “bystanders” were used as the control group. Fifteen percent of students reported being bullied, 7% said they bullied others, and 4% were both bullies and victims.

Only 27% of the victims and 30% of the bully-victims said they had reported their victimization to another person.

Victims were twice as likely feel unsafe at school, sad on most days, and “no good at all,” compared with bystanders, and after controlling for age, gender, ethnicity, and income status. They also were more likely to say that they didn't feel as if they belonged at their school.

Academic performance was significantly associated with being a victim; for every 1-point rise in grade point average, the odds of being a victim dropped by 10%. But victims were not more likely than bystanders to endorse the high-risk behaviors.

Bullies were almost twice as likely to report feeling unsafe at school and sad on most days, compared with bystanders. They were three times as likely to endorse the idea of beating up someone who starts a fight, and twice as likely to say it's OK to pick a fight or to cheat at school.

In addition, the investigators found that bully-victims were 2.5 times more likely to feel unsafe and to report feeling “no good at all” and twice as likely to report daily sadness, compared with bystanders. They also were three times more likely to say it was all right to bring a gun to school and to cheat. “There are many reasons why adolescents might endorse carrying a gun to school,” Dr. Glew and her associates said, noting a 2000 report that found 66% of school shooters reported feeling “bullied, attacked, threatened, or persecuted prior to the incident.”

The investigators' own findings are “consistent with the literature, which suggests that the bully-victim group is the most troubled.”

The study was supported by a grant from the National Institutes of Mental Health; none of the investigators reported a conflict of interest.

Adolescents who are involved in bullying–either as a victim, bully, or both–are more likely than bystanders to report feelings of low self-worth and sadness and to feel unsafe in their school.

These issues are most troubling in children who are both bullies and victims, Dr. Gwen M. Glew and her colleagues reported. The findings suggest, “that we should be particularly concerned about [these children] because they are much more likely to endorse carrying a gun to school,” the investigators wrote (J. Ped. 2008;152:123–8).

Dr. Glew of the University of Washington, Seattle, and her associates surveyed 5,391 children from a single urban public school district in grades 7, 9, and 11. The students rated how often they bullied and were victims of bullying; their feelings of safety at school; their feelings of self-worth and daily sadness; and their judgments on the high-risk behaviors of bringing a gun to school, fighting, cheating, stealing, smoking, and drinking alcohol.

The researchers also obtained grade point averages for all surveyed students.

Overall, 74% of the students reported being neither a bully nor victim–these “bystanders” were used as the control group. Fifteen percent of students reported being bullied, 7% said they bullied others, and 4% were both bullies and victims.

Only 27% of the victims and 30% of the bully-victims said they had reported their victimization to another person.

Victims were twice as likely feel unsafe at school, sad on most days, and “no good at all,” compared with bystanders, and after controlling for age, gender, ethnicity, and income status. They also were more likely to say that they didn't feel as if they belonged at their school.

Academic performance was significantly associated with being a victim; for every 1-point rise in grade point average, the odds of being a victim dropped by 10%. But victims were not more likely than bystanders to endorse the high-risk behaviors.

Bullies were almost twice as likely to report feeling unsafe at school and sad on most days, compared with bystanders. They were three times as likely to endorse the idea of beating up someone who starts a fight, and twice as likely to say it's OK to pick a fight or to cheat at school.

In addition, the investigators found that bully-victims were 2.5 times more likely to feel unsafe and to report feeling “no good at all” and twice as likely to report daily sadness, compared with bystanders. They also were three times more likely to say it was all right to bring a gun to school and to cheat. “There are many reasons why adolescents might endorse carrying a gun to school,” Dr. Glew and her associates said, noting a 2000 report that found 66% of school shooters reported feeling “bullied, attacked, threatened, or persecuted prior to the incident.”

The investigators' own findings are “consistent with the literature, which suggests that the bully-victim group is the most troubled.”

The study was supported by a grant from the National Institutes of Mental Health; none of the investigators reported a conflict of interest.

CHICAGO — More than 3 million teenage girls have at least one sexually transmitted disease, and 15% of those have multiple infections, according to the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD, according to the population-based study sponsored by the Centers for Disease Control and Prevention. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common infections, compared with 20% of white teens, investigators reported during a CDC-sponsored conference on STD prevention.

"For any other disease, we would be calling this an epidemic," said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention. "These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs."

The study's lead author, Dr. Sara Forhan of the CDC, extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues. As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present.

The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted. The gonorrhea rates were not publicly available at the time of her analysis. Syphilis and HIV were excluded because they are not typically found in this age group. "We did test for syphilis and gonorrhea in women aged 18–41, and in the 18- and 19-year-olds, who were also included in my analysis, there were no cases." The survey identified an overall STD rate of 26%, she said. "This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer." The most prevalent STD was cancer- and genital wart-associated HPV, affecting 18% of participants. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%. Among the teens who had an STD, 15% had more than one type of infection.

These infections occur quickly after sexual debut, Dr. Forhan noted. "Of particular importance is how fast these infections appear," she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection: 50% of teens who reported three or more partners had at least one of the STDs.

The survey also showed sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD (48% vs. 20%).

"While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection," Dr. Forhan said.

The results underscore the importance of HPV vaccination for 11- and 12-year-olds, as well as chlamydia screening for all sexually active women under age 25, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention.

Of the adolescent girls studied, 4% were found to be infected with chlamydia. CDC/Dr. E. Arum/Dr. N. Jacobs

CHICAGO — More than 3 million teenage girls have at least one sexually transmitted disease, and 15% of those have multiple infections, according to the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD, according to the population-based study sponsored by the Centers for Disease Control and Prevention. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common infections, compared with 20% of white teens, investigators reported during a CDC-sponsored conference on STD prevention.

"For any other disease, we would be calling this an epidemic," said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention. "These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs."

The study's lead author, Dr. Sara Forhan of the CDC, extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues. As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present.

The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted. The gonorrhea rates were not publicly available at the time of her analysis. Syphilis and HIV were excluded because they are not typically found in this age group. "We did test for syphilis and gonorrhea in women aged 18–41, and in the 18- and 19-year-olds, who were also included in my analysis, there were no cases." The survey identified an overall STD rate of 26%, she said. "This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer." The most prevalent STD was cancer- and genital wart-associated HPV, affecting 18% of participants. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%. Among the teens who had an STD, 15% had more than one type of infection.

These infections occur quickly after sexual debut, Dr. Forhan noted. "Of particular importance is how fast these infections appear," she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection: 50% of teens who reported three or more partners had at least one of the STDs.

The survey also showed sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD (48% vs. 20%).

"While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection," Dr. Forhan said.

The results underscore the importance of HPV vaccination for 11- and 12-year-olds, as well as chlamydia screening for all sexually active women under age 25, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention.

Of the adolescent girls studied, 4% were found to be infected with chlamydia. CDC/Dr. E. Arum/Dr. N. Jacobs

CHICAGO — More than 3 million teenage girls have at least one sexually transmitted disease, and 15% of those have multiple infections, according to the first large study of STDs in this population.

Overall, 26% of 14- to 19-year-olds were infected with at least one STD, according to the population-based study sponsored by the Centers for Disease Control and Prevention. Black teens had the highest prevalence of disease, with 48% testing positive for at least one of the four most common infections, compared with 20% of white teens, investigators reported during a CDC-sponsored conference on STD prevention.

"For any other disease, we would be calling this an epidemic," said Dr. John M. Douglas Jr., director of the CDC's Division of STD Prevention. "These high infection rates among young women, particularly African American women, are clear signs that we must continue developing ways to reach those at most risk. Screening and early treatment can prevent some of the most devastating effects of untreated STDs."

The study's lead author, Dr. Sara Forhan of the CDC, extracted her data from the 2003–2004 National Health and Nutrition Examination Survey, a continuous annual study that examines a nationally representative sample of U.S. households to assess a broad range of health issues. As part of the 2003–2004 survey, 838 girls aged 14–19 years underwent STD testing for human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. The teens underwent urine and blood testing and provided a self-collected vaginal swab to determine if an infection was present.

The analysis excluded the prevalence of gonorrhea, syphilis, and HIV infections, Dr. Forhan noted. The gonorrhea rates were not publicly available at the time of her analysis. Syphilis and HIV were excluded because they are not typically found in this age group. "We did test for syphilis and gonorrhea in women aged 18–41, and in the 18- and 19-year-olds, who were also included in my analysis, there were no cases." The survey identified an overall STD rate of 26%, she said. "This means that one-quarter of our female adolescent population in the [United States]—3.2 million girls—has at least one of the STDs that most commonly affect women. Far too many girls face the risk of serious effects from these diseases, including infertility and cancer." The most prevalent STD was cancer- and genital wart-associated HPV, affecting 18% of participants. Chlamydia was found in 4%, trichomoniasis in 2.5%, and herpes simplex virus type 2 in 2%. Among the teens who had an STD, 15% had more than one type of infection.

These infections occur quickly after sexual debut, Dr. Forhan noted. "Of particular importance is how fast these infections appear," she said. Among those who reported just 1 year of sexual activity, the prevalence already was 20%. Increased sexual activity leads to increased risk of infection: 50% of teens who reported three or more partners had at least one of the STDs.

The survey also showed sharp racial differences in STD prevalence, with black teens more than twice as likely as whites to have at least one STD (48% vs. 20%).

"While race itself is not a risk factor for an STD, the realities of life for many African American girls—limited access to health care, poverty, and a higher community prevalence of STDs—can all contribute to an increased risk of infection," Dr. Forhan said.

The results underscore the importance of HPV vaccination for 11- and 12-year-olds, as well as chlamydia screening for all sexually active women under age 25, said Dr. Kevin Fenton, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention.

Of the adolescent girls studied, 4% were found to be infected with chlamydia. CDC/Dr. E. Arum/Dr. N. Jacobs

CHICAGO — The rate of syphilis in the United States has increased for the 7th consecutive year, jumping 12% from 2006 to 2007, according to preliminary evidence released by the Centers for Disease Control and Prevention.

The upsurge was driven largely by a 14% rise in cases of primary and secondary syphilis among men, Dr. Hillard Weinstock said at a conference on STD prevention sponsored by the CDC. "As in recent years, the 2007 data show that men—particularly men who have sex with men—account for the vast majority of syphilis cases and contribute significantly to the overall syphilis increases. Men who have sex with men [composed] approximately 64% of reported syphilis cases in 2007," said Dr. Weinstock, chief of surveillance at the CDC's division of STD prevention.

The overall 12% increase reflected about 1,300 additional cases reported to the CDC in 2007—a population rate of 6/100,000, Dr. Weinstock said at a press briefing during the conference. The rate among men was six times greater than that among women. The rate of syphilis among blacks was seven times higher than that among whites.

Black men were 6 times more likely to have the disease than white men were, and black women were 13 times more likely to have it than white women were. From 2006 to 2007, the disease rate rose 25% in black men and 12% in black women.

"While men who have sex with men bear the heaviest burden of syphilis infections, ongoing increases among women and African Americans are also troubling and threaten to undo recent progress," Dr. Weinstock said.

Following a 1999 federal commitment to end syphilis nationwide, infection rates reached an all-time low in 2000, dipping to just two cases per 100,000. The rate has increased each year since then. The new prevalence numbers represent a 76% increase over the 2000 nadir.

Inadequate routine screening combined with complacency about the disease appear to be influencing the increase, said Dr. John M. Douglas, Jr. the director of CDC's division of STD prevention. "When the incidence of a disease decreases so much, we often see an accompanying decrease in recognition of the disease among both providers and the public." The CDC recommends that sexually active gay men receive annual testing for both syphilis and HIV, with more frequent testing recommended for men who engage in high-risk same-sex behavior. But the new prevalence numbers, along with other studies, indicate that the rate of screening is too low.

"We really need help from our health care partners," Dr. Douglas said. "A major message is that the word about the need for annual testing is not getting out to providers."

'A major message is that the word about the need for annual testing is not getting out to providers.' DR. DOUGLAS

CHICAGO — The rate of syphilis in the United States has increased for the 7th consecutive year, jumping 12% from 2006 to 2007, according to preliminary evidence released by the Centers for Disease Control and Prevention.

The upsurge was driven largely by a 14% rise in cases of primary and secondary syphilis among men, Dr. Hillard Weinstock said at a conference on STD prevention sponsored by the CDC. "As in recent years, the 2007 data show that men—particularly men who have sex with men—account for the vast majority of syphilis cases and contribute significantly to the overall syphilis increases. Men who have sex with men [composed] approximately 64% of reported syphilis cases in 2007," said Dr. Weinstock, chief of surveillance at the CDC's division of STD prevention.

The overall 12% increase reflected about 1,300 additional cases reported to the CDC in 2007—a population rate of 6/100,000, Dr. Weinstock said at a press briefing during the conference. The rate among men was six times greater than that among women. The rate of syphilis among blacks was seven times higher than that among whites.

Black men were 6 times more likely to have the disease than white men were, and black women were 13 times more likely to have it than white women were. From 2006 to 2007, the disease rate rose 25% in black men and 12% in black women.

"While men who have sex with men bear the heaviest burden of syphilis infections, ongoing increases among women and African Americans are also troubling and threaten to undo recent progress," Dr. Weinstock said.

Following a 1999 federal commitment to end syphilis nationwide, infection rates reached an all-time low in 2000, dipping to just two cases per 100,000. The rate has increased each year since then. The new prevalence numbers represent a 76% increase over the 2000 nadir.

Inadequate routine screening combined with complacency about the disease appear to be influencing the increase, said Dr. John M. Douglas, Jr. the director of CDC's division of STD prevention. "When the incidence of a disease decreases so much, we often see an accompanying decrease in recognition of the disease among both providers and the public." The CDC recommends that sexually active gay men receive annual testing for both syphilis and HIV, with more frequent testing recommended for men who engage in high-risk same-sex behavior. But the new prevalence numbers, along with other studies, indicate that the rate of screening is too low.

"We really need help from our health care partners," Dr. Douglas said. "A major message is that the word about the need for annual testing is not getting out to providers."

'A major message is that the word about the need for annual testing is not getting out to providers.' DR. DOUGLAS

CHICAGO — The rate of syphilis in the United States has increased for the 7th consecutive year, jumping 12% from 2006 to 2007, according to preliminary evidence released by the Centers for Disease Control and Prevention.

The upsurge was driven largely by a 14% rise in cases of primary and secondary syphilis among men, Dr. Hillard Weinstock said at a conference on STD prevention sponsored by the CDC. "As in recent years, the 2007 data show that men—particularly men who have sex with men—account for the vast majority of syphilis cases and contribute significantly to the overall syphilis increases. Men who have sex with men [composed] approximately 64% of reported syphilis cases in 2007," said Dr. Weinstock, chief of surveillance at the CDC's division of STD prevention.

The overall 12% increase reflected about 1,300 additional cases reported to the CDC in 2007—a population rate of 6/100,000, Dr. Weinstock said at a press briefing during the conference. The rate among men was six times greater than that among women. The rate of syphilis among blacks was seven times higher than that among whites.

Black men were 6 times more likely to have the disease than white men were, and black women were 13 times more likely to have it than white women were. From 2006 to 2007, the disease rate rose 25% in black men and 12% in black women.

"While men who have sex with men bear the heaviest burden of syphilis infections, ongoing increases among women and African Americans are also troubling and threaten to undo recent progress," Dr. Weinstock said.

Following a 1999 federal commitment to end syphilis nationwide, infection rates reached an all-time low in 2000, dipping to just two cases per 100,000. The rate has increased each year since then. The new prevalence numbers represent a 76% increase over the 2000 nadir.

Inadequate routine screening combined with complacency about the disease appear to be influencing the increase, said Dr. John M. Douglas, Jr. the director of CDC's division of STD prevention. "When the incidence of a disease decreases so much, we often see an accompanying decrease in recognition of the disease among both providers and the public." The CDC recommends that sexually active gay men receive annual testing for both syphilis and HIV, with more frequent testing recommended for men who engage in high-risk same-sex behavior. But the new prevalence numbers, along with other studies, indicate that the rate of screening is too low.

"We really need help from our health care partners," Dr. Douglas said. "A major message is that the word about the need for annual testing is not getting out to providers."

'A major message is that the word about the need for annual testing is not getting out to providers.' DR. DOUGLAS

Children born as a result of in vitro fertilization have significantly higher blood pressure and fasting glucose levels than do those conceived naturally—a finding suggestive of fetal programming during an early developmental window, Dr. Manon Ceelen and colleagues reported.

Although the possible mechanism behind this finding remains unknown, the study “underscores the importance of the continuing worldwide monitoring of postnatal development of IVF children,” Dr. Ceelen and her coauthors wrote in theJournal of Clinical Endocrinology and Metabolism (2008 Feb. 19 [doi:10.1210/jc.2007–2432]).

Dr. Ceelen and her coauthors of the Free University Medical Center, Amsterdam, compared the cardiometabolic measurements of 225 IVF and 225 naturally conceived children (average age, 12 years).

The parents of all the children had been part of a Dutch study on the long-term health effects of hormone stimulation in 26,400 subfertile women. Of this group, 20,000 women received IVF treatment.

Compared with naturally conceived children, those conceived through IVF weighed significantly less on average at birth (3.2 vs. 3.4 kg).

In addition, there were significantly more preterm infants among the IVF group (29 vs. 6).

Average systolic blood pressure was significantly higher in IVF children than in the control group (109 mm Hg vs. 105 mm Hg); mean diastolic blood pressure was also significantly higher in the IVF group (61 mm Hg vs. 59 mm Hg).

Children born via IVF were twice as likely as those naturally conceived were to have a systolic blood pressure of at least 114 mm Hg and to have a diastolic blood pressure of at least 65 mm Hg.

Those in the IVF group had significantly greater average sum of skinfolds measurement (40 mm vs. 37 mm), although there were no significant differences in weight or body mass index between the groups.

Significantly higher mean fasting glucose measurements were seen in the IVF group (5 mmol/L vs. 4.8 mmol/L).

IVF children were 2.5 times more likely to have a fasting glucose level of at least 5.2 mmol/L.

These relationships remained significant even after the investigators adjusted for confounders (birth weight, gestational age, sum of skinfolds measurement, parity, and the cause of the mother's subfertility).

Although the differences in blood pressure appear small on an individual level, they could have significant health implications on a population level, the investigators wrote.

“A slight increase in blood pressure is associated with a remarkably increased risk of developing cardiovascular disease. … Furthermore, it cannot be excluded that raised blood pressure after IVF may be amplified throughout life, as blood pressure is known to track from childhood into adult life,” they noted.

The authors could not explain the observed relationships between IVF and cardiometabolic status. Both population and animal studies show a link between prenatal environment and early gestational development.

For instance, maternal malnutrition in early pregnancy has been linked to later cardiovascular disease in the offspring. “Preconceptional undernutrition has been associated with the precocious activation of the hypothalamo-pituitary-adrenal axis,” the authors wrote.

They said this premature activation might be associated with fetal programming effects.

However, the investigators wrote, “it remains to be elucidated whether increased blood pressure among IVF children originates from early prenatal life adaptations mediated through neuroendocrineal pathways related to the HPA axis and/or through one of the unidentified mechanisms.”

Children born as a result of in vitro fertilization have significantly higher blood pressure and fasting glucose levels than do those conceived naturally—a finding suggestive of fetal programming during an early developmental window, Dr. Manon Ceelen and colleagues reported.

Although the possible mechanism behind this finding remains unknown, the study “underscores the importance of the continuing worldwide monitoring of postnatal development of IVF children,” Dr. Ceelen and her coauthors wrote in theJournal of Clinical Endocrinology and Metabolism (2008 Feb. 19 [doi:10.1210/jc.2007–2432]).

Dr. Ceelen and her coauthors of the Free University Medical Center, Amsterdam, compared the cardiometabolic measurements of 225 IVF and 225 naturally conceived children (average age, 12 years).

The parents of all the children had been part of a Dutch study on the long-term health effects of hormone stimulation in 26,400 subfertile women. Of this group, 20,000 women received IVF treatment.

Compared with naturally conceived children, those conceived through IVF weighed significantly less on average at birth (3.2 vs. 3.4 kg).

In addition, there were significantly more preterm infants among the IVF group (29 vs. 6).

Average systolic blood pressure was significantly higher in IVF children than in the control group (109 mm Hg vs. 105 mm Hg); mean diastolic blood pressure was also significantly higher in the IVF group (61 mm Hg vs. 59 mm Hg).

Children born via IVF were twice as likely as those naturally conceived were to have a systolic blood pressure of at least 114 mm Hg and to have a diastolic blood pressure of at least 65 mm Hg.

Those in the IVF group had significantly greater average sum of skinfolds measurement (40 mm vs. 37 mm), although there were no significant differences in weight or body mass index between the groups.

Significantly higher mean fasting glucose measurements were seen in the IVF group (5 mmol/L vs. 4.8 mmol/L).

IVF children were 2.5 times more likely to have a fasting glucose level of at least 5.2 mmol/L.

These relationships remained significant even after the investigators adjusted for confounders (birth weight, gestational age, sum of skinfolds measurement, parity, and the cause of the mother's subfertility).

Although the differences in blood pressure appear small on an individual level, they could have significant health implications on a population level, the investigators wrote.

“A slight increase in blood pressure is associated with a remarkably increased risk of developing cardiovascular disease. … Furthermore, it cannot be excluded that raised blood pressure after IVF may be amplified throughout life, as blood pressure is known to track from childhood into adult life,” they noted.

The authors could not explain the observed relationships between IVF and cardiometabolic status. Both population and animal studies show a link between prenatal environment and early gestational development.

For instance, maternal malnutrition in early pregnancy has been linked to later cardiovascular disease in the offspring. “Preconceptional undernutrition has been associated with the precocious activation of the hypothalamo-pituitary-adrenal axis,” the authors wrote.

They said this premature activation might be associated with fetal programming effects.

However, the investigators wrote, “it remains to be elucidated whether increased blood pressure among IVF children originates from early prenatal life adaptations mediated through neuroendocrineal pathways related to the HPA axis and/or through one of the unidentified mechanisms.”

Children born as a result of in vitro fertilization have significantly higher blood pressure and fasting glucose levels than do those conceived naturally—a finding suggestive of fetal programming during an early developmental window, Dr. Manon Ceelen and colleagues reported.

Although the possible mechanism behind this finding remains unknown, the study “underscores the importance of the continuing worldwide monitoring of postnatal development of IVF children,” Dr. Ceelen and her coauthors wrote in theJournal of Clinical Endocrinology and Metabolism (2008 Feb. 19 [doi:10.1210/jc.2007–2432]).

Dr. Ceelen and her coauthors of the Free University Medical Center, Amsterdam, compared the cardiometabolic measurements of 225 IVF and 225 naturally conceived children (average age, 12 years).

The parents of all the children had been part of a Dutch study on the long-term health effects of hormone stimulation in 26,400 subfertile women. Of this group, 20,000 women received IVF treatment.

Compared with naturally conceived children, those conceived through IVF weighed significantly less on average at birth (3.2 vs. 3.4 kg).

In addition, there were significantly more preterm infants among the IVF group (29 vs. 6).

Average systolic blood pressure was significantly higher in IVF children than in the control group (109 mm Hg vs. 105 mm Hg); mean diastolic blood pressure was also significantly higher in the IVF group (61 mm Hg vs. 59 mm Hg).

Children born via IVF were twice as likely as those naturally conceived were to have a systolic blood pressure of at least 114 mm Hg and to have a diastolic blood pressure of at least 65 mm Hg.

Those in the IVF group had significantly greater average sum of skinfolds measurement (40 mm vs. 37 mm), although there were no significant differences in weight or body mass index between the groups.

Significantly higher mean fasting glucose measurements were seen in the IVF group (5 mmol/L vs. 4.8 mmol/L).

IVF children were 2.5 times more likely to have a fasting glucose level of at least 5.2 mmol/L.

These relationships remained significant even after the investigators adjusted for confounders (birth weight, gestational age, sum of skinfolds measurement, parity, and the cause of the mother's subfertility).

Although the differences in blood pressure appear small on an individual level, they could have significant health implications on a population level, the investigators wrote.

“A slight increase in blood pressure is associated with a remarkably increased risk of developing cardiovascular disease. … Furthermore, it cannot be excluded that raised blood pressure after IVF may be amplified throughout life, as blood pressure is known to track from childhood into adult life,” they noted.

The authors could not explain the observed relationships between IVF and cardiometabolic status. Both population and animal studies show a link between prenatal environment and early gestational development.

For instance, maternal malnutrition in early pregnancy has been linked to later cardiovascular disease in the offspring. “Preconceptional undernutrition has been associated with the precocious activation of the hypothalamo-pituitary-adrenal axis,” the authors wrote.

They said this premature activation might be associated with fetal programming effects.

However, the investigators wrote, “it remains to be elucidated whether increased blood pressure among IVF children originates from early prenatal life adaptations mediated through neuroendocrineal pathways related to the HPA axis and/or through one of the unidentified mechanisms.”

BOSTON — Tenofovir suppresses viral load more rapidly and effectively than adefovir does in patients with HBe antigen-negative chronic hepatitis B, Dr. Patrick Marcellin reported at the annual meeting of the American Association for the Study of Liver Diseases.

Although both patient groups experienced a rapid decline in viral load by week 4 of the 48-week trial, those taking tenofovir experienced a steeper decline and a higher response rate, and the response was maintained, said Dr. Marcellin of the Hospital Beaujon, Clichy, France.

In the phase III trial, 375 patients with chronic hepatitis B infection were randomized to either 300 mg/day tenofovir or 10 mg/day adefovir. The primary end points were suppression of viral DNA to below 400 copies/mL and reduction of at least 2 points in the Knodell necroinflammatory score without worsening of fibrosis.

The patients' mean age was 44 years, and their mean necroinflammation score was 8. Twenty percent had cirrhosis. At baseline, mean hepatitis B virus RNA levels were about 7 log10 c/mL.

Both groups achieved rapid suppression of hepatitis B virus DNA, with the majority of responsive patients doing so by week 4. By week 48, however, response differences emerged. Significantly more tenofovir-treated patients than adefovir-treated patients achieved viral loads below 400 copies/mL (93% versus 63%, respectively).

There was no significant difference in histologic response between the two groups: 72% treated with tenofovir improved, versus 69% treated with adefovir. But there was a significant difference in the percentage of patients who achieved both virologic and histologic response: 71% of the tenofovir group, versus 49% of the adefovir group.

At week 48, the ALT level was normal in 77% of both groups. The incidence of ALT flare was about 1% in each group. There were no significant differences in amylase, lipase, or creatinine levels. Regarding drug resistance, none of the tenofovir-treated patients developed resistant mutations.

The phase III study was sponsored by Gilead Sciences Inc., Durham, N.C., the company that manufactures tenofovir. Dr. Marcellin disclosed he has a financial relationship with Gilead Sciences.

BOSTON — Tenofovir suppresses viral load more rapidly and effectively than adefovir does in patients with HBe antigen-negative chronic hepatitis B, Dr. Patrick Marcellin reported at the annual meeting of the American Association for the Study of Liver Diseases.

Although both patient groups experienced a rapid decline in viral load by week 4 of the 48-week trial, those taking tenofovir experienced a steeper decline and a higher response rate, and the response was maintained, said Dr. Marcellin of the Hospital Beaujon, Clichy, France.

In the phase III trial, 375 patients with chronic hepatitis B infection were randomized to either 300 mg/day tenofovir or 10 mg/day adefovir. The primary end points were suppression of viral DNA to below 400 copies/mL and reduction of at least 2 points in the Knodell necroinflammatory score without worsening of fibrosis.

The patients' mean age was 44 years, and their mean necroinflammation score was 8. Twenty percent had cirrhosis. At baseline, mean hepatitis B virus RNA levels were about 7 log10 c/mL.

Both groups achieved rapid suppression of hepatitis B virus DNA, with the majority of responsive patients doing so by week 4. By week 48, however, response differences emerged. Significantly more tenofovir-treated patients than adefovir-treated patients achieved viral loads below 400 copies/mL (93% versus 63%, respectively).

There was no significant difference in histologic response between the two groups: 72% treated with tenofovir improved, versus 69% treated with adefovir. But there was a significant difference in the percentage of patients who achieved both virologic and histologic response: 71% of the tenofovir group, versus 49% of the adefovir group.

At week 48, the ALT level was normal in 77% of both groups. The incidence of ALT flare was about 1% in each group. There were no significant differences in amylase, lipase, or creatinine levels. Regarding drug resistance, none of the tenofovir-treated patients developed resistant mutations.

The phase III study was sponsored by Gilead Sciences Inc., Durham, N.C., the company that manufactures tenofovir. Dr. Marcellin disclosed he has a financial relationship with Gilead Sciences.

BOSTON — Tenofovir suppresses viral load more rapidly and effectively than adefovir does in patients with HBe antigen-negative chronic hepatitis B, Dr. Patrick Marcellin reported at the annual meeting of the American Association for the Study of Liver Diseases.

Although both patient groups experienced a rapid decline in viral load by week 4 of the 48-week trial, those taking tenofovir experienced a steeper decline and a higher response rate, and the response was maintained, said Dr. Marcellin of the Hospital Beaujon, Clichy, France.

In the phase III trial, 375 patients with chronic hepatitis B infection were randomized to either 300 mg/day tenofovir or 10 mg/day adefovir. The primary end points were suppression of viral DNA to below 400 copies/mL and reduction of at least 2 points in the Knodell necroinflammatory score without worsening of fibrosis.

The patients' mean age was 44 years, and their mean necroinflammation score was 8. Twenty percent had cirrhosis. At baseline, mean hepatitis B virus RNA levels were about 7 log10 c/mL.

Both groups achieved rapid suppression of hepatitis B virus DNA, with the majority of responsive patients doing so by week 4. By week 48, however, response differences emerged. Significantly more tenofovir-treated patients than adefovir-treated patients achieved viral loads below 400 copies/mL (93% versus 63%, respectively).

There was no significant difference in histologic response between the two groups: 72% treated with tenofovir improved, versus 69% treated with adefovir. But there was a significant difference in the percentage of patients who achieved both virologic and histologic response: 71% of the tenofovir group, versus 49% of the adefovir group.

At week 48, the ALT level was normal in 77% of both groups. The incidence of ALT flare was about 1% in each group. There were no significant differences in amylase, lipase, or creatinine levels. Regarding drug resistance, none of the tenofovir-treated patients developed resistant mutations.

The phase III study was sponsored by Gilead Sciences Inc., Durham, N.C., the company that manufactures tenofovir. Dr. Marcellin disclosed he has a financial relationship with Gilead Sciences.

Cholinesterase inhibitors and memantine are not one-size-fits-all drugs that can be prescribed to every patient with dementia and should only be employed after assessing each drug's risk/benefit profile in light of an individual patient's needs, according to a new set of clinical guidelines.

“The most important thing to keep in mind is that there is no cure for dementia,” said Dr. Amir Qaseem, author of the guidelines and a member of the Joint American College of Physicians/American Academy of Family Physicians Panel on Dementia.

“These drugs can only alleviate symptoms and may slightly delay progression. But they should not be prescribed to every dementia patient because the benefits are very modest and some patients may not show benefit at all, and all the drugs carry potential harms.”

Although many patients do show statistically significant improvements while taking the drugs, most of those changes are small and not clinically meaningful, according to the guidelines (Ann. Intern. Med. 2008;148:370–8).

The panel also concluded that there is insufficient evidence to recommended one drug over another for the treatment of dementia. Instead, “the choice of therapy should be based on an evaluation of adverse events, tolerability, and cost, because there is no evidence that one treatment is more effective than another,” Dr. Qaseem said in an interview.

The recommendations are particularly important for primary care physicians, who care for most patients with dementia, said Dr. William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.

“[Most] dementia patients are being managed by primary care physicians, and this is going to increase,” he said in an interview. “As these guidelines point out, the emphasis when treating these patients should be that the physician, patient, and family work as a unit to decide the best use of a medication and the best time to stop.”

The guidelines panel mined data from 59 studies that examined any of the five drugs approved for dementia treatment in the United States (donepezil, rivastigmine, galantamine, tacrine, and memantine). Drugs were assessed for their effects on symptoms (cognition, function, and behavior), quality of life, and their adverse event profile. The results of this evidence review accompany the guidelines (Ann. Int. Med. 2008;148:379–97).

The largest body of high-quality evidence was seen for donepezil: Twenty-four studies compared it with either placebo or vitamin E. Most showed statistically significant effects in favor of the drug for at least one measure of cognition. Improvements in function also were reported. Nine studies also showed that these improvements were clinically meaningful. “These findings are important because although the average improvement in cognition … did not reach statistical significance, a subset of patients may have clinical improvement,” the panel noted. Up to 57% of patients discontinued their donepezil because of adverse events; the most commonly reported were gastrointestinal upset and muscle cramps.

Ten studies examined the use of galantamine. It was associated with statistically significant, but not clinically important, improvements in cognition and behavior. Withdrawal because of adverse events ranged from 8% to 57%, with the most common being gastrointestinal symptoms, eating disorders, weight loss, and dizziness.

Rivastigmine was assessed in nine placebo-controlled studies. Overall, there was significant but very inconsistent cognitive benefit, and no significant benefits on behavior or quality of life. Up to 29% of patients withdrew because of adverse events, including dizziness, nausea and vomiting, diarrhea, weight loss, and headache.

Eight studies examined the use of tacrine; seven were placebo-controlled and one compared tacrine with idebenone. One trial showed a significant cognitive benefit and three showed significant benefit in function; there were no effects on behavior or quality of life. Up to 55% of patients discontinued the drug, which was associated with serious adverse events, including hepatic abnormalities and abnormal liver enzymes. The panel concluded that there was insufficient evidence to substantiate any benefit of tacrine on cognition or behavior.

Memantine, the only neuropeptide-modifying agent available in the United States, was assessed in five studies, all of which compared the drug with placebo. Three trials showed significant, but not clinically important, improvements in cognition. One study showed significant improvements in behavior, and three showed significant quality of life benefits. The withdrawal rate varied from 9% to 12%. Adverse events included nausea, dizziness, diarrhea, and agitation.

The panel found only three high-quality head-to-head trials. Two pitted donepezil against galantamine. A 52-week study showed no significant difference in the primary outcome of function. An 8-week trial, favored galantamine for cognition.

The third trial compared donepezil with rivastigmine over 2 years. Patients taking rivastigmine fared significantly better in function and some measures of behavior, but experienced more adverse events than did those receiving donepezil.

The guideline writing panel attempted to address the appropriate duration of therapy; however the response to pharmacotherapy varies so widely. Generally, the beneficial effect from any of the drugs—disease stabilization or symptom improvement—will be apparent within 3 months of initiating treatment but will be temporary. When slowing decline is no longer a therapeutic goal, “treatment with a cholinesterase inhibitor or memantine is no longer appropriate.”

Honest communication at the time of diagnosis is the best way to optimize medical therapy, said Dr. David A. Smith, a professor of family medicine at Texas A&M University, College Station. When families and patients understand up front that the benefit from these drugs will be modest and temporary, they are more likely to stick with the treatment plan, squeezing every possible benefit from it.

“A lot of people do get started on these drugs, but the dropout rate is huge, because there is [an] expectation of large benefit,” he said. “It's important to remember that even small changes in cognition and behavior can roll into bigger changes over time, like in the rate of institutionalization.”

Dr. Thies agreed. Despite their limitations, “These drugs are the best that we have at this point, and you don't want patients to throw away the only opportunity that we do have. You want the patient and family to go into therapy with a rational view of what is going to happen. The more they know about what to expect, the better they will do.”

Early diagnosis is key to getting everyone on the same page about expectations. “If someone with Alzheimer's is to get into this discussion in a rational fashion, early diagnosis is critical. That way, patients can be involved in determining not only the course of therapy, but [also] can express their opinions on placement and end-of-life care. These questions become much easier if the patient is involved, rather than having the family guess about his wishes at a later point.”

Cholinesterase inhibitors and memantine are not one-size-fits-all drugs that can be prescribed to every patient with dementia and should only be employed after assessing each drug's risk/benefit profile in light of an individual patient's needs, according to a new set of clinical guidelines.

“The most important thing to keep in mind is that there is no cure for dementia,” said Dr. Amir Qaseem, author of the guidelines and a member of the Joint American College of Physicians/American Academy of Family Physicians Panel on Dementia.

“These drugs can only alleviate symptoms and may slightly delay progression. But they should not be prescribed to every dementia patient because the benefits are very modest and some patients may not show benefit at all, and all the drugs carry potential harms.”

Although many patients do show statistically significant improvements while taking the drugs, most of those changes are small and not clinically meaningful, according to the guidelines (Ann. Intern. Med. 2008;148:370–8).

The panel also concluded that there is insufficient evidence to recommended one drug over another for the treatment of dementia. Instead, “the choice of therapy should be based on an evaluation of adverse events, tolerability, and cost, because there is no evidence that one treatment is more effective than another,” Dr. Qaseem said in an interview.

The recommendations are particularly important for primary care physicians, who care for most patients with dementia, said Dr. William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.

“[Most] dementia patients are being managed by primary care physicians, and this is going to increase,” he said in an interview. “As these guidelines point out, the emphasis when treating these patients should be that the physician, patient, and family work as a unit to decide the best use of a medication and the best time to stop.”

The guidelines panel mined data from 59 studies that examined any of the five drugs approved for dementia treatment in the United States (donepezil, rivastigmine, galantamine, tacrine, and memantine). Drugs were assessed for their effects on symptoms (cognition, function, and behavior), quality of life, and their adverse event profile. The results of this evidence review accompany the guidelines (Ann. Int. Med. 2008;148:379–97).

The largest body of high-quality evidence was seen for donepezil: Twenty-four studies compared it with either placebo or vitamin E. Most showed statistically significant effects in favor of the drug for at least one measure of cognition. Improvements in function also were reported. Nine studies also showed that these improvements were clinically meaningful. “These findings are important because although the average improvement in cognition … did not reach statistical significance, a subset of patients may have clinical improvement,” the panel noted. Up to 57% of patients discontinued their donepezil because of adverse events; the most commonly reported were gastrointestinal upset and muscle cramps.

Ten studies examined the use of galantamine. It was associated with statistically significant, but not clinically important, improvements in cognition and behavior. Withdrawal because of adverse events ranged from 8% to 57%, with the most common being gastrointestinal symptoms, eating disorders, weight loss, and dizziness.

Rivastigmine was assessed in nine placebo-controlled studies. Overall, there was significant but very inconsistent cognitive benefit, and no significant benefits on behavior or quality of life. Up to 29% of patients withdrew because of adverse events, including dizziness, nausea and vomiting, diarrhea, weight loss, and headache.

Eight studies examined the use of tacrine; seven were placebo-controlled and one compared tacrine with idebenone. One trial showed a significant cognitive benefit and three showed significant benefit in function; there were no effects on behavior or quality of life. Up to 55% of patients discontinued the drug, which was associated with serious adverse events, including hepatic abnormalities and abnormal liver enzymes. The panel concluded that there was insufficient evidence to substantiate any benefit of tacrine on cognition or behavior.

Memantine, the only neuropeptide-modifying agent available in the United States, was assessed in five studies, all of which compared the drug with placebo. Three trials showed significant, but not clinically important, improvements in cognition. One study showed significant improvements in behavior, and three showed significant quality of life benefits. The withdrawal rate varied from 9% to 12%. Adverse events included nausea, dizziness, diarrhea, and agitation.

The panel found only three high-quality head-to-head trials. Two pitted donepezil against galantamine. A 52-week study showed no significant difference in the primary outcome of function. An 8-week trial, favored galantamine for cognition.

The third trial compared donepezil with rivastigmine over 2 years. Patients taking rivastigmine fared significantly better in function and some measures of behavior, but experienced more adverse events than did those receiving donepezil.

The guideline writing panel attempted to address the appropriate duration of therapy; however the response to pharmacotherapy varies so widely. Generally, the beneficial effect from any of the drugs—disease stabilization or symptom improvement—will be apparent within 3 months of initiating treatment but will be temporary. When slowing decline is no longer a therapeutic goal, “treatment with a cholinesterase inhibitor or memantine is no longer appropriate.”

Honest communication at the time of diagnosis is the best way to optimize medical therapy, said Dr. David A. Smith, a professor of family medicine at Texas A&M University, College Station. When families and patients understand up front that the benefit from these drugs will be modest and temporary, they are more likely to stick with the treatment plan, squeezing every possible benefit from it.

“A lot of people do get started on these drugs, but the dropout rate is huge, because there is [an] expectation of large benefit,” he said. “It's important to remember that even small changes in cognition and behavior can roll into bigger changes over time, like in the rate of institutionalization.”

Dr. Thies agreed. Despite their limitations, “These drugs are the best that we have at this point, and you don't want patients to throw away the only opportunity that we do have. You want the patient and family to go into therapy with a rational view of what is going to happen. The more they know about what to expect, the better they will do.”

Early diagnosis is key to getting everyone on the same page about expectations. “If someone with Alzheimer's is to get into this discussion in a rational fashion, early diagnosis is critical. That way, patients can be involved in determining not only the course of therapy, but [also] can express their opinions on placement and end-of-life care. These questions become much easier if the patient is involved, rather than having the family guess about his wishes at a later point.”

Cholinesterase inhibitors and memantine are not one-size-fits-all drugs that can be prescribed to every patient with dementia and should only be employed after assessing each drug's risk/benefit profile in light of an individual patient's needs, according to a new set of clinical guidelines.

“The most important thing to keep in mind is that there is no cure for dementia,” said Dr. Amir Qaseem, author of the guidelines and a member of the Joint American College of Physicians/American Academy of Family Physicians Panel on Dementia.

“These drugs can only alleviate symptoms and may slightly delay progression. But they should not be prescribed to every dementia patient because the benefits are very modest and some patients may not show benefit at all, and all the drugs carry potential harms.”

Although many patients do show statistically significant improvements while taking the drugs, most of those changes are small and not clinically meaningful, according to the guidelines (Ann. Intern. Med. 2008;148:370–8).

The panel also concluded that there is insufficient evidence to recommended one drug over another for the treatment of dementia. Instead, “the choice of therapy should be based on an evaluation of adverse events, tolerability, and cost, because there is no evidence that one treatment is more effective than another,” Dr. Qaseem said in an interview.

The recommendations are particularly important for primary care physicians, who care for most patients with dementia, said Dr. William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.

“[Most] dementia patients are being managed by primary care physicians, and this is going to increase,” he said in an interview. “As these guidelines point out, the emphasis when treating these patients should be that the physician, patient, and family work as a unit to decide the best use of a medication and the best time to stop.”

The guidelines panel mined data from 59 studies that examined any of the five drugs approved for dementia treatment in the United States (donepezil, rivastigmine, galantamine, tacrine, and memantine). Drugs were assessed for their effects on symptoms (cognition, function, and behavior), quality of life, and their adverse event profile. The results of this evidence review accompany the guidelines (Ann. Int. Med. 2008;148:379–97).

The largest body of high-quality evidence was seen for donepezil: Twenty-four studies compared it with either placebo or vitamin E. Most showed statistically significant effects in favor of the drug for at least one measure of cognition. Improvements in function also were reported. Nine studies also showed that these improvements were clinically meaningful. “These findings are important because although the average improvement in cognition … did not reach statistical significance, a subset of patients may have clinical improvement,” the panel noted. Up to 57% of patients discontinued their donepezil because of adverse events; the most commonly reported were gastrointestinal upset and muscle cramps.

Ten studies examined the use of galantamine. It was associated with statistically significant, but not clinically important, improvements in cognition and behavior. Withdrawal because of adverse events ranged from 8% to 57%, with the most common being gastrointestinal symptoms, eating disorders, weight loss, and dizziness.

Rivastigmine was assessed in nine placebo-controlled studies. Overall, there was significant but very inconsistent cognitive benefit, and no significant benefits on behavior or quality of life. Up to 29% of patients withdrew because of adverse events, including dizziness, nausea and vomiting, diarrhea, weight loss, and headache.

Eight studies examined the use of tacrine; seven were placebo-controlled and one compared tacrine with idebenone. One trial showed a significant cognitive benefit and three showed significant benefit in function; there were no effects on behavior or quality of life. Up to 55% of patients discontinued the drug, which was associated with serious adverse events, including hepatic abnormalities and abnormal liver enzymes. The panel concluded that there was insufficient evidence to substantiate any benefit of tacrine on cognition or behavior.

Memantine, the only neuropeptide-modifying agent available in the United States, was assessed in five studies, all of which compared the drug with placebo. Three trials showed significant, but not clinically important, improvements in cognition. One study showed significant improvements in behavior, and three showed significant quality of life benefits. The withdrawal rate varied from 9% to 12%. Adverse events included nausea, dizziness, diarrhea, and agitation.

The panel found only three high-quality head-to-head trials. Two pitted donepezil against galantamine. A 52-week study showed no significant difference in the primary outcome of function. An 8-week trial, favored galantamine for cognition.

The third trial compared donepezil with rivastigmine over 2 years. Patients taking rivastigmine fared significantly better in function and some measures of behavior, but experienced more adverse events than did those receiving donepezil.

The guideline writing panel attempted to address the appropriate duration of therapy; however the response to pharmacotherapy varies so widely. Generally, the beneficial effect from any of the drugs—disease stabilization or symptom improvement—will be apparent within 3 months of initiating treatment but will be temporary. When slowing decline is no longer a therapeutic goal, “treatment with a cholinesterase inhibitor or memantine is no longer appropriate.”

Honest communication at the time of diagnosis is the best way to optimize medical therapy, said Dr. David A. Smith, a professor of family medicine at Texas A&M University, College Station. When families and patients understand up front that the benefit from these drugs will be modest and temporary, they are more likely to stick with the treatment plan, squeezing every possible benefit from it.

“A lot of people do get started on these drugs, but the dropout rate is huge, because there is [an] expectation of large benefit,” he said. “It's important to remember that even small changes in cognition and behavior can roll into bigger changes over time, like in the rate of institutionalization.”

Dr. Thies agreed. Despite their limitations, “These drugs are the best that we have at this point, and you don't want patients to throw away the only opportunity that we do have. You want the patient and family to go into therapy with a rational view of what is going to happen. The more they know about what to expect, the better they will do.”

Early diagnosis is key to getting everyone on the same page about expectations. “If someone with Alzheimer's is to get into this discussion in a rational fashion, early diagnosis is critical. That way, patients can be involved in determining not only the course of therapy, but [also] can express their opinions on placement and end-of-life care. These questions become much easier if the patient is involved, rather than having the family guess about his wishes at a later point.”

WASHINGTON — For patients with severe critical limb ischemia and medical comorbidities, subintimal angioplasty is a safer and less expensive alternative to bypass surgery, and is just as effective at preventing amputation, according to the results of a randomized, single-surgeon study.

“These findings have caused a paradigm shift in the way we manage critical limb ischemia in these patients,” Dr. Niamh Hynes said at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The 5-year, randomized controlled trial compared subintimal angioplasty with bypass surgery in 309 patients with severe critical limb ischemia. The average age was 72 years, and all patients had severe lesions (level C and D according to the Transatlantic InterSociety Consensus [TASC] Classification system). Diabetes was present in 22%; all patients had a high medical comorbidity score.

Subintimal angioplasty was performed in 190 patients; 119 underwent bypass surgery, according to Dr. Hynes of University College Hospital, Galway, Ireland. The procedures were performed by a single surgeon, Dr. Sherif Sultan, at the hospital from 2002 to 2007.

At 5 years, primary patency rates were greater, but not significantly so, in the angioplasty group (73% vs. 65%). Neither the use of a stent nor the number of stents employed significantly affected patency rates. No blood marker (homocysteine, glucose level, C-reactive protein, or fibrinogen levels) was associated with patency rates.

Angioplasty also was associated with better primary assisted patency and secondary patency rates at 5 years, although these differences were not statistically significant.

Both interventions were effective at maintaining amputation-free survival (angioplasty 73%, bypass 71%) and all-cause survival (77% and 80%) at 5 years. At 5 years, 68% of angioplasty patients were free from major adverse events, compared with 57% of bypass patients, a significant difference.

When short-term results were considered, angioplasty appeared at least as successful as bypass surgery. All-cause 30-day mortality was half that seen with bypass, although the difference was not significant (1.6% vs. 3%). Length of hospital stay was significantly shorter (14 vs. 24 days).

Angioplasty was significantly less expensive than bypass surgery (&z.euro;11,650 vs. &z.euro;18,700). When cost was broken down by quality-adjusted life-year, angioplasty also was significantly less expensive (cost per QALY &z.euro;5,660 vs. &z.euro;9,170).

WASHINGTON — For patients with severe critical limb ischemia and medical comorbidities, subintimal angioplasty is a safer and less expensive alternative to bypass surgery, and is just as effective at preventing amputation, according to the results of a randomized, single-surgeon study.

“These findings have caused a paradigm shift in the way we manage critical limb ischemia in these patients,” Dr. Niamh Hynes said at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The 5-year, randomized controlled trial compared subintimal angioplasty with bypass surgery in 309 patients with severe critical limb ischemia. The average age was 72 years, and all patients had severe lesions (level C and D according to the Transatlantic InterSociety Consensus [TASC] Classification system). Diabetes was present in 22%; all patients had a high medical comorbidity score.

Subintimal angioplasty was performed in 190 patients; 119 underwent bypass surgery, according to Dr. Hynes of University College Hospital, Galway, Ireland. The procedures were performed by a single surgeon, Dr. Sherif Sultan, at the hospital from 2002 to 2007.

At 5 years, primary patency rates were greater, but not significantly so, in the angioplasty group (73% vs. 65%). Neither the use of a stent nor the number of stents employed significantly affected patency rates. No blood marker (homocysteine, glucose level, C-reactive protein, or fibrinogen levels) was associated with patency rates.

Angioplasty also was associated with better primary assisted patency and secondary patency rates at 5 years, although these differences were not statistically significant.

Both interventions were effective at maintaining amputation-free survival (angioplasty 73%, bypass 71%) and all-cause survival (77% and 80%) at 5 years. At 5 years, 68% of angioplasty patients were free from major adverse events, compared with 57% of bypass patients, a significant difference.

When short-term results were considered, angioplasty appeared at least as successful as bypass surgery. All-cause 30-day mortality was half that seen with bypass, although the difference was not significant (1.6% vs. 3%). Length of hospital stay was significantly shorter (14 vs. 24 days).

Angioplasty was significantly less expensive than bypass surgery (&z.euro;11,650 vs. &z.euro;18,700). When cost was broken down by quality-adjusted life-year, angioplasty also was significantly less expensive (cost per QALY &z.euro;5,660 vs. &z.euro;9,170).

WASHINGTON — For patients with severe critical limb ischemia and medical comorbidities, subintimal angioplasty is a safer and less expensive alternative to bypass surgery, and is just as effective at preventing amputation, according to the results of a randomized, single-surgeon study.

“These findings have caused a paradigm shift in the way we manage critical limb ischemia in these patients,” Dr. Niamh Hynes said at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The 5-year, randomized controlled trial compared subintimal angioplasty with bypass surgery in 309 patients with severe critical limb ischemia. The average age was 72 years, and all patients had severe lesions (level C and D according to the Transatlantic InterSociety Consensus [TASC] Classification system). Diabetes was present in 22%; all patients had a high medical comorbidity score.

Subintimal angioplasty was performed in 190 patients; 119 underwent bypass surgery, according to Dr. Hynes of University College Hospital, Galway, Ireland. The procedures were performed by a single surgeon, Dr. Sherif Sultan, at the hospital from 2002 to 2007.

At 5 years, primary patency rates were greater, but not significantly so, in the angioplasty group (73% vs. 65%). Neither the use of a stent nor the number of stents employed significantly affected patency rates. No blood marker (homocysteine, glucose level, C-reactive protein, or fibrinogen levels) was associated with patency rates.

Angioplasty also was associated with better primary assisted patency and secondary patency rates at 5 years, although these differences were not statistically significant.

Both interventions were effective at maintaining amputation-free survival (angioplasty 73%, bypass 71%) and all-cause survival (77% and 80%) at 5 years. At 5 years, 68% of angioplasty patients were free from major adverse events, compared with 57% of bypass patients, a significant difference.

When short-term results were considered, angioplasty appeared at least as successful as bypass surgery. All-cause 30-day mortality was half that seen with bypass, although the difference was not significant (1.6% vs. 3%). Length of hospital stay was significantly shorter (14 vs. 24 days).

Angioplasty was significantly less expensive than bypass surgery (&z.euro;11,650 vs. &z.euro;18,700). When cost was broken down by quality-adjusted life-year, angioplasty also was significantly less expensive (cost per QALY &z.euro;5,660 vs. &z.euro;9,170).