Mary Ann Moon

HPV vaccination should be targeted at preadolescent girls, with initial "catch-up" programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be "observable for decades," so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as "the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care."

Assuming that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000–$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a "catch-up" program to vaccinate girls aged 13–21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value.

Both the routine vaccination of 12-year-olds and the "catch-up" vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and boosters will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor in chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model "well done and ambitious."

"There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?" she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to "develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention," as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts. The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

HPV vaccination should be targeted at preadolescent girls, with initial "catch-up" programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be "observable for decades," so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as "the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care."

Assuming that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000–$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a "catch-up" program to vaccinate girls aged 13–21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value.

Both the routine vaccination of 12-year-olds and the "catch-up" vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and boosters will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor in chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model "well done and ambitious."

"There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?" she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to "develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention," as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts. The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

HPV vaccination should be targeted at preadolescent girls, with initial "catch-up" programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be "observable for decades," so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as "the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care."

Assuming that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000–$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a "catch-up" program to vaccinate girls aged 13–21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value.

Both the routine vaccination of 12-year-olds and the "catch-up" vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and boosters will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor in chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model "well done and ambitious."

"There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?" she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to "develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention," as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts. The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

Sildenafil reduced the adverse sexual effects related to treatment with serotonin reuptake inhibitors in women who had major depression in remission in a randomized trial of 98 women.

“These findings are important not only because women experience major depressive disorder at nearly double the rate of men and because they experience greater resulting sexual dysfunction than men, but also because [they established] that selective phosphodiesterase type 5 inhibitors are effective” for reducing adverse sexual effects in women, Dr. H. George Nurnberg of the department of psychiatry, University of New Mexico Health Sciences Center, Albuquerque, and his associates said in a report in JAMA.

The researchers compared sildenafil with placebo in an 8-week randomized clinical trial with 98 premenopausal women who had major depressive disorder in remission. The participants in the study, which was supported by Pfizer Inc., reported persistent sexual dysfunction and had been taking selective or nonselective SRIs for a mean of 27 months.

Treatment efficacy was assessed using four measures: the Clinical Global Impressions Scale adapted for sexual function, the Sexual Function Questionnaire, the Arizona Sexual Experience Scale (female version), and the University of New Mexico Sexual Function Inventory (female version).

At the end of treatment, women in the sildenafil group reported a greater ability to reach orgasm and to experience orgasm satisfaction than did those in the placebo group. They also were more likely to report improvements in arousal, vaginal lubrication, and orgasm delay, the last of which “is considered a central feature of SRI-associated sexual dysfunction,” the investigators said.

“Clinically, 73% of women taking placebo, compared with 28% of women taking sildenafil, reported no improvement with treatment,” Dr. Nurnberg and his associates said (JAMA 2008;300:395–404).

There were no serious adverse events. The most common minor adverse events were headache (affecting 43% of the sildenafil group and 27% of the placebo group), flushing (24% vs. 0%), dyspepsia (12% vs. 0%), nasal congestion (37% vs. 6%), and transient visual disturbances (14% vs. 2%).

Treating the sexual dysfunction that affects up to 70% of women treated with SRIs should encourage patients to adhere to antidepressant therapy and thus improve outcomes, the researchers added.

Dr. Nurnberg has received research support from, has been a paid consultant for, and has been on speakers bureaus for various pharmaceutical companies that manufacture antidepressants.

Sildenafil reduced the adverse sexual effects related to treatment with serotonin reuptake inhibitors in women who had major depression in remission in a randomized trial of 98 women.

“These findings are important not only because women experience major depressive disorder at nearly double the rate of men and because they experience greater resulting sexual dysfunction than men, but also because [they established] that selective phosphodiesterase type 5 inhibitors are effective” for reducing adverse sexual effects in women, Dr. H. George Nurnberg of the department of psychiatry, University of New Mexico Health Sciences Center, Albuquerque, and his associates said in a report in JAMA.

The researchers compared sildenafil with placebo in an 8-week randomized clinical trial with 98 premenopausal women who had major depressive disorder in remission. The participants in the study, which was supported by Pfizer Inc., reported persistent sexual dysfunction and had been taking selective or nonselective SRIs for a mean of 27 months.

Treatment efficacy was assessed using four measures: the Clinical Global Impressions Scale adapted for sexual function, the Sexual Function Questionnaire, the Arizona Sexual Experience Scale (female version), and the University of New Mexico Sexual Function Inventory (female version).

At the end of treatment, women in the sildenafil group reported a greater ability to reach orgasm and to experience orgasm satisfaction than did those in the placebo group. They also were more likely to report improvements in arousal, vaginal lubrication, and orgasm delay, the last of which “is considered a central feature of SRI-associated sexual dysfunction,” the investigators said.

“Clinically, 73% of women taking placebo, compared with 28% of women taking sildenafil, reported no improvement with treatment,” Dr. Nurnberg and his associates said (JAMA 2008;300:395–404).

There were no serious adverse events. The most common minor adverse events were headache (affecting 43% of the sildenafil group and 27% of the placebo group), flushing (24% vs. 0%), dyspepsia (12% vs. 0%), nasal congestion (37% vs. 6%), and transient visual disturbances (14% vs. 2%).

Treating the sexual dysfunction that affects up to 70% of women treated with SRIs should encourage patients to adhere to antidepressant therapy and thus improve outcomes, the researchers added.

Dr. Nurnberg has received research support from, has been a paid consultant for, and has been on speakers bureaus for various pharmaceutical companies that manufacture antidepressants.

Sildenafil reduced the adverse sexual effects related to treatment with serotonin reuptake inhibitors in women who had major depression in remission in a randomized trial of 98 women.

“These findings are important not only because women experience major depressive disorder at nearly double the rate of men and because they experience greater resulting sexual dysfunction than men, but also because [they established] that selective phosphodiesterase type 5 inhibitors are effective” for reducing adverse sexual effects in women, Dr. H. George Nurnberg of the department of psychiatry, University of New Mexico Health Sciences Center, Albuquerque, and his associates said in a report in JAMA.

The researchers compared sildenafil with placebo in an 8-week randomized clinical trial with 98 premenopausal women who had major depressive disorder in remission. The participants in the study, which was supported by Pfizer Inc., reported persistent sexual dysfunction and had been taking selective or nonselective SRIs for a mean of 27 months.

Treatment efficacy was assessed using four measures: the Clinical Global Impressions Scale adapted for sexual function, the Sexual Function Questionnaire, the Arizona Sexual Experience Scale (female version), and the University of New Mexico Sexual Function Inventory (female version).

At the end of treatment, women in the sildenafil group reported a greater ability to reach orgasm and to experience orgasm satisfaction than did those in the placebo group. They also were more likely to report improvements in arousal, vaginal lubrication, and orgasm delay, the last of which “is considered a central feature of SRI-associated sexual dysfunction,” the investigators said.

“Clinically, 73% of women taking placebo, compared with 28% of women taking sildenafil, reported no improvement with treatment,” Dr. Nurnberg and his associates said (JAMA 2008;300:395–404).

There were no serious adverse events. The most common minor adverse events were headache (affecting 43% of the sildenafil group and 27% of the placebo group), flushing (24% vs. 0%), dyspepsia (12% vs. 0%), nasal congestion (37% vs. 6%), and transient visual disturbances (14% vs. 2%).

Treating the sexual dysfunction that affects up to 70% of women treated with SRIs should encourage patients to adhere to antidepressant therapy and thus improve outcomes, the researchers added.

Dr. Nurnberg has received research support from, has been a paid consultant for, and has been on speakers bureaus for various pharmaceutical companies that manufacture antidepressants.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a results of a mathematical model.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a “catch-up” program to vaccinate girls aged 13–21 years also was found to be reasonably cost effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value. Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and booster vaccines will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as the investigators have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a results of a mathematical model.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a “catch-up” program to vaccinate girls aged 13–21 years also was found to be reasonably cost effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value. Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and booster vaccines will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as the investigators have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a results of a mathematical model.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston. They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost effectiveness ratio of $43,600 per quality-adjusted life year gained. This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821–32).

Adding a “catch-up” program to vaccinate girls aged 13–21 years also was found to be reasonably cost effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model. However, extending such a catch-up program to women older than 21 was not found to be a good value. Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years. In that case, continued screening and booster vaccines will be necessary and will add substantially to costs.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs. How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861–2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as the investigators have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted. Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers did not report any potential conflicts of interest.

Tibolone reduced the risk of vertebral and nonvertebral fractures as well as breast cancer in a large international clinical trial involving older women with osteoporosis, but it also raised the risk of stroke, researchers said.

The drug also appeared to reduce the risk of colon cancer in this study, but tripled the rate of vaginal bleeding and endometrial thickening that required biopsy, reported Dr. Steven R. Cummings and his associates in the Long-Term Intervention on Fractures with Tibolone (LIFT) study.

Tibolone is approved for treating menopausal symptoms in 90 countries and for treating osteoporosis in 45, but is not approved for either indication in the United States.

The LIFT study, sponsored by Organon, compared daily tibolone with placebo in 4,538 osteoporotic women aged 60–85 years who were treated at 80 medical centers in 22 countries. About 26% of these subjects had already had a vertebral fracture.

The trial was halted early, after a median of 34 months of treatment, when an interim analysis showed that the drug doubled the risk of stroke, particularly during the first year of use and in women aged older than 70 years. That analysis also showed that tibolone met the criteria for efficacy in preventing fractures.

At the time the study was stopped, more than 90% of the subjects had received at least 80% of their scheduled doses of tibolone or placebo.

The data showed that tibolone decreased the relative risk of vertebral fracture by 45% and the relative risk of nonvertebral fractures by 26%, said Dr. Cummings of the California Pacific Medical Center Research Institute and the University of California, San Francisco, and his associates.

The drug appeared to be particularly effective at preventing fractures in women who had already had a vertebral fracture, reducing the relative risk of further vertebral fracture by 61% and the relative risk of nonvertebral fracture by 47%, the investigators said (N. Engl. J. Med. 2008;359: 697–708).

The magnitude of these bone effects was similar to that reported for estrogen, bisphosphonate, and raloxifene therapy.

Tibolone also cut the relative risk of breast cancer by 68%, a reduction similar to that reported for tamoxifen or raloxifene.

It is not clear why the drug was found to prevent breast cancer in this study when it was found to raise the risk of the disease in previous observational studies, Dr. Cummings and his colleagues noted.

Compared with placebo, tibolone appeared to decrease the rate of colon cancer. It showed no significant effect on other cancers.

Tibolone more than doubled the risk of stroke. “Among patients 70 years of age or older, the risk of stroke was 6.6 per 1,000 person-years in the tibolone group and 3.4 per 1,000 person-years in the placebo group,” the researchers said.

The drug therefore is contraindicated in women older than 70 and “in women who have strong risk factors for stroke, such as hypertension, smoking, diabetes, and atrial fibrillation.”

Nearly 10% of women receiving tibolone reported abnormal vaginal bleeding, and 499 of them required endometrial biopsy, compared with only 136 women taking placebo.

Four women in the tibolone group developed endometrial cancer, compared with none in the placebo group.

Other adverse effects of tibolone included weight gain, breast pain, vaginal discharge and infection, pelvic pain, and elevations in liver enzymes.

Nineteen percent of the tibolone group discontinued treatment because of adverse events, compared with 13% of the placebo group.

Tibolone did not appear to have a deleterious effect on venous thromboembolism or coronary heart disease events. However, this study was not adequately powered to assess the drug's effects on these cardiovascular outcomes.

Dr. Cummings reported that he has received consulting fees from, or has served on a paid advisory board for, Pfizer, Amgen, Eli Lilly & Co., GlaxoSmith-Kline, Procter & Gamble, and Organon.

It's not clear why the drug was found to prevent breast cancer when it was found to raise the risk in previous studies. DR. CUMMINGS

Tibolone reduced the risk of vertebral and nonvertebral fractures as well as breast cancer in a large international clinical trial involving older women with osteoporosis, but it also raised the risk of stroke, researchers said.

The drug also appeared to reduce the risk of colon cancer in this study, but tripled the rate of vaginal bleeding and endometrial thickening that required biopsy, reported Dr. Steven R. Cummings and his associates in the Long-Term Intervention on Fractures with Tibolone (LIFT) study.

Tibolone is approved for treating menopausal symptoms in 90 countries and for treating osteoporosis in 45, but is not approved for either indication in the United States.

The LIFT study, sponsored by Organon, compared daily tibolone with placebo in 4,538 osteoporotic women aged 60–85 years who were treated at 80 medical centers in 22 countries. About 26% of these subjects had already had a vertebral fracture.

The trial was halted early, after a median of 34 months of treatment, when an interim analysis showed that the drug doubled the risk of stroke, particularly during the first year of use and in women aged older than 70 years. That analysis also showed that tibolone met the criteria for efficacy in preventing fractures.

At the time the study was stopped, more than 90% of the subjects had received at least 80% of their scheduled doses of tibolone or placebo.

The data showed that tibolone decreased the relative risk of vertebral fracture by 45% and the relative risk of nonvertebral fractures by 26%, said Dr. Cummings of the California Pacific Medical Center Research Institute and the University of California, San Francisco, and his associates.

The drug appeared to be particularly effective at preventing fractures in women who had already had a vertebral fracture, reducing the relative risk of further vertebral fracture by 61% and the relative risk of nonvertebral fracture by 47%, the investigators said (N. Engl. J. Med. 2008;359: 697–708).

The magnitude of these bone effects was similar to that reported for estrogen, bisphosphonate, and raloxifene therapy.

Tibolone also cut the relative risk of breast cancer by 68%, a reduction similar to that reported for tamoxifen or raloxifene.

It is not clear why the drug was found to prevent breast cancer in this study when it was found to raise the risk of the disease in previous observational studies, Dr. Cummings and his colleagues noted.

Compared with placebo, tibolone appeared to decrease the rate of colon cancer. It showed no significant effect on other cancers.

Tibolone more than doubled the risk of stroke. “Among patients 70 years of age or older, the risk of stroke was 6.6 per 1,000 person-years in the tibolone group and 3.4 per 1,000 person-years in the placebo group,” the researchers said.

The drug therefore is contraindicated in women older than 70 and “in women who have strong risk factors for stroke, such as hypertension, smoking, diabetes, and atrial fibrillation.”

Nearly 10% of women receiving tibolone reported abnormal vaginal bleeding, and 499 of them required endometrial biopsy, compared with only 136 women taking placebo.

Four women in the tibolone group developed endometrial cancer, compared with none in the placebo group.

Other adverse effects of tibolone included weight gain, breast pain, vaginal discharge and infection, pelvic pain, and elevations in liver enzymes.

Nineteen percent of the tibolone group discontinued treatment because of adverse events, compared with 13% of the placebo group.

Tibolone did not appear to have a deleterious effect on venous thromboembolism or coronary heart disease events. However, this study was not adequately powered to assess the drug's effects on these cardiovascular outcomes.

Dr. Cummings reported that he has received consulting fees from, or has served on a paid advisory board for, Pfizer, Amgen, Eli Lilly & Co., GlaxoSmith-Kline, Procter & Gamble, and Organon.

It's not clear why the drug was found to prevent breast cancer when it was found to raise the risk in previous studies. DR. CUMMINGS

Tibolone reduced the risk of vertebral and nonvertebral fractures as well as breast cancer in a large international clinical trial involving older women with osteoporosis, but it also raised the risk of stroke, researchers said.

The drug also appeared to reduce the risk of colon cancer in this study, but tripled the rate of vaginal bleeding and endometrial thickening that required biopsy, reported Dr. Steven R. Cummings and his associates in the Long-Term Intervention on Fractures with Tibolone (LIFT) study.

Tibolone is approved for treating menopausal symptoms in 90 countries and for treating osteoporosis in 45, but is not approved for either indication in the United States.

The LIFT study, sponsored by Organon, compared daily tibolone with placebo in 4,538 osteoporotic women aged 60–85 years who were treated at 80 medical centers in 22 countries. About 26% of these subjects had already had a vertebral fracture.

The trial was halted early, after a median of 34 months of treatment, when an interim analysis showed that the drug doubled the risk of stroke, particularly during the first year of use and in women aged older than 70 years. That analysis also showed that tibolone met the criteria for efficacy in preventing fractures.

At the time the study was stopped, more than 90% of the subjects had received at least 80% of their scheduled doses of tibolone or placebo.

The data showed that tibolone decreased the relative risk of vertebral fracture by 45% and the relative risk of nonvertebral fractures by 26%, said Dr. Cummings of the California Pacific Medical Center Research Institute and the University of California, San Francisco, and his associates.

The drug appeared to be particularly effective at preventing fractures in women who had already had a vertebral fracture, reducing the relative risk of further vertebral fracture by 61% and the relative risk of nonvertebral fracture by 47%, the investigators said (N. Engl. J. Med. 2008;359: 697–708).

The magnitude of these bone effects was similar to that reported for estrogen, bisphosphonate, and raloxifene therapy.

Tibolone also cut the relative risk of breast cancer by 68%, a reduction similar to that reported for tamoxifen or raloxifene.

It is not clear why the drug was found to prevent breast cancer in this study when it was found to raise the risk of the disease in previous observational studies, Dr. Cummings and his colleagues noted.

Compared with placebo, tibolone appeared to decrease the rate of colon cancer. It showed no significant effect on other cancers.

Tibolone more than doubled the risk of stroke. “Among patients 70 years of age or older, the risk of stroke was 6.6 per 1,000 person-years in the tibolone group and 3.4 per 1,000 person-years in the placebo group,” the researchers said.

The drug therefore is contraindicated in women older than 70 and “in women who have strong risk factors for stroke, such as hypertension, smoking, diabetes, and atrial fibrillation.”

Nearly 10% of women receiving tibolone reported abnormal vaginal bleeding, and 499 of them required endometrial biopsy, compared with only 136 women taking placebo.

Four women in the tibolone group developed endometrial cancer, compared with none in the placebo group.

Other adverse effects of tibolone included weight gain, breast pain, vaginal discharge and infection, pelvic pain, and elevations in liver enzymes.

Nineteen percent of the tibolone group discontinued treatment because of adverse events, compared with 13% of the placebo group.

Tibolone did not appear to have a deleterious effect on venous thromboembolism or coronary heart disease events. However, this study was not adequately powered to assess the drug's effects on these cardiovascular outcomes.

Dr. Cummings reported that he has received consulting fees from, or has served on a paid advisory board for, Pfizer, Amgen, Eli Lilly & Co., GlaxoSmith-Kline, Procter & Gamble, and Organon.

It's not clear why the drug was found to prevent breast cancer when it was found to raise the risk in previous studies. DR. CUMMINGS

A noninvasive imaging method that measures metabolic stress in the retina will likely become very useful in detecting diabetes early and monitoring disease progression, researchers said.

In a small study published in the Archives of Ophthalmology, levels of flavoprotein autofluorescence in the retina were found to distinguish between subjects with diabetes and control subjects, regardless of disease duration or severity.

“Hyperglycemia induces mitochondrial stress and apoptotic cell death in diabetic tissues soon after disease onset and before involvement can be detected by any other current clinical diagnostic method,” said Matthew G. Field of the University of Michigan, Ann Arbor, and his associates.

Abnormally increased oxidation of mitochondrial flavoproteins causes them to emit green autofluorescence, which can be measured in the retina using a modified fundus camera and customized computer hardware and software.

Mr. Field and his associates measured flavoprotein autofluorescence in 21 subjects with type 1 or type 2 diabetes (mean disease duration, 10 years) and 21 age-matched healthy control subjects who had normal glucose tolerance, blood pressure, and lipid profiles.

The subjects with diabetes consistently showed significantly elevated levels of retinal flavoprotein autofluorescence, compared with controls, regardless of whether retinopathy was present.

“In fact, 9 of 21 cases had no visible retinopathy, indicating that retinal metabolic stress due to diabetes is present before any visible retinopathy,” the investigators said (Arch. Ophthalmol. 2008;126:934–8).

Two of Mr. Field's associates have founded OcuSciences Inc. to commercialize the technology used in this study. Mr. Field did not disclose any conflicts of interest.

A noninvasive imaging method that measures metabolic stress in the retina will likely become very useful in detecting diabetes early and monitoring disease progression, researchers said.

In a small study published in the Archives of Ophthalmology, levels of flavoprotein autofluorescence in the retina were found to distinguish between subjects with diabetes and control subjects, regardless of disease duration or severity.

“Hyperglycemia induces mitochondrial stress and apoptotic cell death in diabetic tissues soon after disease onset and before involvement can be detected by any other current clinical diagnostic method,” said Matthew G. Field of the University of Michigan, Ann Arbor, and his associates.

Abnormally increased oxidation of mitochondrial flavoproteins causes them to emit green autofluorescence, which can be measured in the retina using a modified fundus camera and customized computer hardware and software.

Mr. Field and his associates measured flavoprotein autofluorescence in 21 subjects with type 1 or type 2 diabetes (mean disease duration, 10 years) and 21 age-matched healthy control subjects who had normal glucose tolerance, blood pressure, and lipid profiles.

The subjects with diabetes consistently showed significantly elevated levels of retinal flavoprotein autofluorescence, compared with controls, regardless of whether retinopathy was present.

“In fact, 9 of 21 cases had no visible retinopathy, indicating that retinal metabolic stress due to diabetes is present before any visible retinopathy,” the investigators said (Arch. Ophthalmol. 2008;126:934–8).

Two of Mr. Field's associates have founded OcuSciences Inc. to commercialize the technology used in this study. Mr. Field did not disclose any conflicts of interest.

A noninvasive imaging method that measures metabolic stress in the retina will likely become very useful in detecting diabetes early and monitoring disease progression, researchers said.

In a small study published in the Archives of Ophthalmology, levels of flavoprotein autofluorescence in the retina were found to distinguish between subjects with diabetes and control subjects, regardless of disease duration or severity.

“Hyperglycemia induces mitochondrial stress and apoptotic cell death in diabetic tissues soon after disease onset and before involvement can be detected by any other current clinical diagnostic method,” said Matthew G. Field of the University of Michigan, Ann Arbor, and his associates.

Abnormally increased oxidation of mitochondrial flavoproteins causes them to emit green autofluorescence, which can be measured in the retina using a modified fundus camera and customized computer hardware and software.

Mr. Field and his associates measured flavoprotein autofluorescence in 21 subjects with type 1 or type 2 diabetes (mean disease duration, 10 years) and 21 age-matched healthy control subjects who had normal glucose tolerance, blood pressure, and lipid profiles.

The subjects with diabetes consistently showed significantly elevated levels of retinal flavoprotein autofluorescence, compared with controls, regardless of whether retinopathy was present.

“In fact, 9 of 21 cases had no visible retinopathy, indicating that retinal metabolic stress due to diabetes is present before any visible retinopathy,” the investigators said (Arch. Ophthalmol. 2008;126:934–8).

Two of Mr. Field's associates have founded OcuSciences Inc. to commercialize the technology used in this study. Mr. Field did not disclose any conflicts of interest.

Plasma vitamin C level as well as fruit and vegetable intake shows a “striking” inverse relation with the risk of developing diabetes, according to a prospective study.

Compared with men and women in the lowest quintile of plasma vitamin C, those in the highest quintile have a 62% lower chance of developing diabetes, said Dr. Anne-Helen Harding of the Institute of Metabolic Science at Addenbrooke's Hospital, Cambridge (England), and her associates. People who were in the top quintile of fruit and vegetable consumption had a 22% lower chance of developing diabetes.

“Plasma vitamin C level is a good candidate to act as a biomarker for fruit and vegetable consumption because in Western diets, fruit and vegetable consumption is the main source of vitamin C,” the investigators wrote (Arch. Intern. Med. 2008;168:1493–9).

They concluded that, “the findings suggest that eating even a small quantity of fruit and vegetables may be beneficial and that the protection against diabetes increases progressively” with the quantity consumed.

To the investigators' knowledge, “no published studies have examined the association of plasma vitamin C level and incident diabetes.” While previous studies found lower plasma vitamin C levels in people with diabetes compared to people without diabetes, those studies “cannot establish the temporal sequence of events” whether low plasma vitamin C precedes diabetes or is a consequence of the condition.

The aim of the current study was “to investigate the prospective association between plasma vitamin C level and the risk of developing type 2 diabetes in a population of middle-aged men and women,” the researchers stated. “An additional aim was to examine the relationship between fruit and vegetable intake and incident diabetes.”

The investigators in the European Prospective Investigation of Cancer-Norfolk Prospective Study assessed the relationship between plasma vitamin C level and diabetes risk in middle-aged men and women using data from a cohort study of 21,831 subjects aged 40–75 years who attended 35 medical practices.

A total of 735 incident cases of diabetes developed during 12 years of follow-up (3.2% incidence). “The cases of diabetes in this study were diagnosed in the community and are likely to be typical of newly diagnosed cases in the general population,” the researchers noted.

The mean plasma vitamin C concentration in people who developed diabetes (0.76 mg/dL) was lower than that in subjects without diabetes (0.95 mg/dL). Moreover, vitamin C level inversely correlated with diabetes risk in a logistic regression analysis.

In a further analysis of the data that adjusted for subject age, sex, family history of diabetes, alcohol intake, physical activity level, smoking status, education level, and social class, this strong inverse association “was materially unchanged” and remained statistically significant, Dr. Harding and her associates said.

In the subset of subjects who had hemoglobin A1c levels of less than 7%, a similar magnitude of association was seen. This analysis effectively excluded cases of diabetes that may have been present but undiagnosed at baseline, the investigators said.

“Our findings re-endorse the public health message of the beneficial effect of increasing total fruit and vegetable intake,” they said.

“Whether the association is causal or a marker for other factors associated with fruit and vegetable intake, signifying a clustering of healthier lifestyles and residual confounding, needs to be addressed in specifically designed studies,” Dr. Harding and her associates added.

The investigators reported no conflicts of interest.

Plasma vitamin C level as well as fruit and vegetable intake shows a “striking” inverse relation with the risk of developing diabetes, according to a prospective study.

Compared with men and women in the lowest quintile of plasma vitamin C, those in the highest quintile have a 62% lower chance of developing diabetes, said Dr. Anne-Helen Harding of the Institute of Metabolic Science at Addenbrooke's Hospital, Cambridge (England), and her associates. People who were in the top quintile of fruit and vegetable consumption had a 22% lower chance of developing diabetes.

“Plasma vitamin C level is a good candidate to act as a biomarker for fruit and vegetable consumption because in Western diets, fruit and vegetable consumption is the main source of vitamin C,” the investigators wrote (Arch. Intern. Med. 2008;168:1493–9).

They concluded that, “the findings suggest that eating even a small quantity of fruit and vegetables may be beneficial and that the protection against diabetes increases progressively” with the quantity consumed.

To the investigators' knowledge, “no published studies have examined the association of plasma vitamin C level and incident diabetes.” While previous studies found lower plasma vitamin C levels in people with diabetes compared to people without diabetes, those studies “cannot establish the temporal sequence of events” whether low plasma vitamin C precedes diabetes or is a consequence of the condition.

The aim of the current study was “to investigate the prospective association between plasma vitamin C level and the risk of developing type 2 diabetes in a population of middle-aged men and women,” the researchers stated. “An additional aim was to examine the relationship between fruit and vegetable intake and incident diabetes.”

The investigators in the European Prospective Investigation of Cancer-Norfolk Prospective Study assessed the relationship between plasma vitamin C level and diabetes risk in middle-aged men and women using data from a cohort study of 21,831 subjects aged 40–75 years who attended 35 medical practices.

A total of 735 incident cases of diabetes developed during 12 years of follow-up (3.2% incidence). “The cases of diabetes in this study were diagnosed in the community and are likely to be typical of newly diagnosed cases in the general population,” the researchers noted.

The mean plasma vitamin C concentration in people who developed diabetes (0.76 mg/dL) was lower than that in subjects without diabetes (0.95 mg/dL). Moreover, vitamin C level inversely correlated with diabetes risk in a logistic regression analysis.

In a further analysis of the data that adjusted for subject age, sex, family history of diabetes, alcohol intake, physical activity level, smoking status, education level, and social class, this strong inverse association “was materially unchanged” and remained statistically significant, Dr. Harding and her associates said.

In the subset of subjects who had hemoglobin A1c levels of less than 7%, a similar magnitude of association was seen. This analysis effectively excluded cases of diabetes that may have been present but undiagnosed at baseline, the investigators said.

“Our findings re-endorse the public health message of the beneficial effect of increasing total fruit and vegetable intake,” they said.

“Whether the association is causal or a marker for other factors associated with fruit and vegetable intake, signifying a clustering of healthier lifestyles and residual confounding, needs to be addressed in specifically designed studies,” Dr. Harding and her associates added.

The investigators reported no conflicts of interest.

Plasma vitamin C level as well as fruit and vegetable intake shows a “striking” inverse relation with the risk of developing diabetes, according to a prospective study.

Compared with men and women in the lowest quintile of plasma vitamin C, those in the highest quintile have a 62% lower chance of developing diabetes, said Dr. Anne-Helen Harding of the Institute of Metabolic Science at Addenbrooke's Hospital, Cambridge (England), and her associates. People who were in the top quintile of fruit and vegetable consumption had a 22% lower chance of developing diabetes.

“Plasma vitamin C level is a good candidate to act as a biomarker for fruit and vegetable consumption because in Western diets, fruit and vegetable consumption is the main source of vitamin C,” the investigators wrote (Arch. Intern. Med. 2008;168:1493–9).

They concluded that, “the findings suggest that eating even a small quantity of fruit and vegetables may be beneficial and that the protection against diabetes increases progressively” with the quantity consumed.

To the investigators' knowledge, “no published studies have examined the association of plasma vitamin C level and incident diabetes.” While previous studies found lower plasma vitamin C levels in people with diabetes compared to people without diabetes, those studies “cannot establish the temporal sequence of events” whether low plasma vitamin C precedes diabetes or is a consequence of the condition.

The aim of the current study was “to investigate the prospective association between plasma vitamin C level and the risk of developing type 2 diabetes in a population of middle-aged men and women,” the researchers stated. “An additional aim was to examine the relationship between fruit and vegetable intake and incident diabetes.”

The investigators in the European Prospective Investigation of Cancer-Norfolk Prospective Study assessed the relationship between plasma vitamin C level and diabetes risk in middle-aged men and women using data from a cohort study of 21,831 subjects aged 40–75 years who attended 35 medical practices.

A total of 735 incident cases of diabetes developed during 12 years of follow-up (3.2% incidence). “The cases of diabetes in this study were diagnosed in the community and are likely to be typical of newly diagnosed cases in the general population,” the researchers noted.

The mean plasma vitamin C concentration in people who developed diabetes (0.76 mg/dL) was lower than that in subjects without diabetes (0.95 mg/dL). Moreover, vitamin C level inversely correlated with diabetes risk in a logistic regression analysis.

In a further analysis of the data that adjusted for subject age, sex, family history of diabetes, alcohol intake, physical activity level, smoking status, education level, and social class, this strong inverse association “was materially unchanged” and remained statistically significant, Dr. Harding and her associates said.

In the subset of subjects who had hemoglobin A1c levels of less than 7%, a similar magnitude of association was seen. This analysis effectively excluded cases of diabetes that may have been present but undiagnosed at baseline, the investigators said.

“Our findings re-endorse the public health message of the beneficial effect of increasing total fruit and vegetable intake,” they said.

“Whether the association is causal or a marker for other factors associated with fruit and vegetable intake, signifying a clustering of healthier lifestyles and residual confounding, needs to be addressed in specifically designed studies,” Dr. Harding and her associates added.

The investigators reported no conflicts of interest.

For patients with cardioembolic stroke, “bridging” therapy with either enoxaparin or heparin until long-term warfarin treatment takes effect raised the risk of serious bleeding, compared with immediately commencing warfarin, a study shows.

In contrast, initiating warfarin shortly after cardioembolic stroke was found to be safe in this single-center retrospective review of 204 patients, according to Dr. Hen Hallevi of the University of Texas at Houston and associates (Arch. Neurol. 2008 July 14 [doi:10.1001/archneur.65.9.noc70105]).

Because this study was retrospective and nonrandomized, the results await validation; they should be viewed as “hypothesis-generating,” and should be interpreted with caution, they noted.

Currently no consensus exists on when and how to institute long-term anticoagulation for secondary stroke prevention in these patients. “Bridging” with enoxaparin or heparin is common practice even though it is not endorsed in published guidelines, the investigators said.

Many clinicians also defer initiating warfarin for fear of precipitating a hypercoagulable state, which “may occur when warfarin is initiated without heparin and may lead to abnormal clotting and skin necrosis,” they said. However, this is an uncommon occurrence in clinical practice, and is usually associated with protein C deficiency, they added.

In this study, all cases of cardioembolic stroke between April 2004 and July 2006 were reviewed. The decisions of whether to use bridging and, if so, whether to use enoxaparin or heparin were “based on clinical judgment and personal preference of the treating physician.”

Thirty-five patients were given warfarin immediately, without any bridging. Forty-four received heparin bridging, and 29 received enoxaparin bridging. Another 8 patients received no anticoagulation therapy, and 88 received aspirin only.

The patients who received no anticoagulation or only aspirin fared poorly and were 12 times more likely to experience stroke progression than those in the other treatment groups.

Heparin bridging was significantly more likely to cause systemic bleeding, and enoxaparin bridging was significantly more likely to cause grade 2 parenchymal hematoma, compared with immediate warfarin.

There were no episodes of skin necrosis in the warfarin group, supporting the observation that this complication is very uncommon in clinical practice and that bridging specifically to prevent skin necrosis is unwarranted, Dr. Hallevi and his associates said

Moreover, there was a clustering of cases of late, symptomatic hemorrhagic transformation “composing an alarming 10%” of the enoxaparin group, with no cases in the warfarin and heparin groups. This suggests a pathophysiologic link between enoxaparin and hemorrhagic transformation, they added.

“Warfarin treatment appears to be safe and can be started at any point during the hospital stay, along with deep vein thrombosis prophylaxis. [In contrast], bridging with a full dose of enoxaparin or heparin may carry a high risk of intracranial and systemic bleeding,” the researchers said.

For patients with cardioembolic stroke, “bridging” therapy with either enoxaparin or heparin until long-term warfarin treatment takes effect raised the risk of serious bleeding, compared with immediately commencing warfarin, a study shows.

In contrast, initiating warfarin shortly after cardioembolic stroke was found to be safe in this single-center retrospective review of 204 patients, according to Dr. Hen Hallevi of the University of Texas at Houston and associates (Arch. Neurol. 2008 July 14 [doi:10.1001/archneur.65.9.noc70105]).

Because this study was retrospective and nonrandomized, the results await validation; they should be viewed as “hypothesis-generating,” and should be interpreted with caution, they noted.

Currently no consensus exists on when and how to institute long-term anticoagulation for secondary stroke prevention in these patients. “Bridging” with enoxaparin or heparin is common practice even though it is not endorsed in published guidelines, the investigators said.

Many clinicians also defer initiating warfarin for fear of precipitating a hypercoagulable state, which “may occur when warfarin is initiated without heparin and may lead to abnormal clotting and skin necrosis,” they said. However, this is an uncommon occurrence in clinical practice, and is usually associated with protein C deficiency, they added.

In this study, all cases of cardioembolic stroke between April 2004 and July 2006 were reviewed. The decisions of whether to use bridging and, if so, whether to use enoxaparin or heparin were “based on clinical judgment and personal preference of the treating physician.”

Thirty-five patients were given warfarin immediately, without any bridging. Forty-four received heparin bridging, and 29 received enoxaparin bridging. Another 8 patients received no anticoagulation therapy, and 88 received aspirin only.

The patients who received no anticoagulation or only aspirin fared poorly and were 12 times more likely to experience stroke progression than those in the other treatment groups.

Heparin bridging was significantly more likely to cause systemic bleeding, and enoxaparin bridging was significantly more likely to cause grade 2 parenchymal hematoma, compared with immediate warfarin.

There were no episodes of skin necrosis in the warfarin group, supporting the observation that this complication is very uncommon in clinical practice and that bridging specifically to prevent skin necrosis is unwarranted, Dr. Hallevi and his associates said

Moreover, there was a clustering of cases of late, symptomatic hemorrhagic transformation “composing an alarming 10%” of the enoxaparin group, with no cases in the warfarin and heparin groups. This suggests a pathophysiologic link between enoxaparin and hemorrhagic transformation, they added.

“Warfarin treatment appears to be safe and can be started at any point during the hospital stay, along with deep vein thrombosis prophylaxis. [In contrast], bridging with a full dose of enoxaparin or heparin may carry a high risk of intracranial and systemic bleeding,” the researchers said.

For patients with cardioembolic stroke, “bridging” therapy with either enoxaparin or heparin until long-term warfarin treatment takes effect raised the risk of serious bleeding, compared with immediately commencing warfarin, a study shows.

In contrast, initiating warfarin shortly after cardioembolic stroke was found to be safe in this single-center retrospective review of 204 patients, according to Dr. Hen Hallevi of the University of Texas at Houston and associates (Arch. Neurol. 2008 July 14 [doi:10.1001/archneur.65.9.noc70105]).

Because this study was retrospective and nonrandomized, the results await validation; they should be viewed as “hypothesis-generating,” and should be interpreted with caution, they noted.

Currently no consensus exists on when and how to institute long-term anticoagulation for secondary stroke prevention in these patients. “Bridging” with enoxaparin or heparin is common practice even though it is not endorsed in published guidelines, the investigators said.

Many clinicians also defer initiating warfarin for fear of precipitating a hypercoagulable state, which “may occur when warfarin is initiated without heparin and may lead to abnormal clotting and skin necrosis,” they said. However, this is an uncommon occurrence in clinical practice, and is usually associated with protein C deficiency, they added.

In this study, all cases of cardioembolic stroke between April 2004 and July 2006 were reviewed. The decisions of whether to use bridging and, if so, whether to use enoxaparin or heparin were “based on clinical judgment and personal preference of the treating physician.”

Thirty-five patients were given warfarin immediately, without any bridging. Forty-four received heparin bridging, and 29 received enoxaparin bridging. Another 8 patients received no anticoagulation therapy, and 88 received aspirin only.

The patients who received no anticoagulation or only aspirin fared poorly and were 12 times more likely to experience stroke progression than those in the other treatment groups.

Heparin bridging was significantly more likely to cause systemic bleeding, and enoxaparin bridging was significantly more likely to cause grade 2 parenchymal hematoma, compared with immediate warfarin.

There were no episodes of skin necrosis in the warfarin group, supporting the observation that this complication is very uncommon in clinical practice and that bridging specifically to prevent skin necrosis is unwarranted, Dr. Hallevi and his associates said

Moreover, there was a clustering of cases of late, symptomatic hemorrhagic transformation “composing an alarming 10%” of the enoxaparin group, with no cases in the warfarin and heparin groups. This suggests a pathophysiologic link between enoxaparin and hemorrhagic transformation, they added.

“Warfarin treatment appears to be safe and can be started at any point during the hospital stay, along with deep vein thrombosis prophylaxis. [In contrast], bridging with a full dose of enoxaparin or heparin may carry a high risk of intracranial and systemic bleeding,” the researchers said.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston.

They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained.

This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821-32).

Adding a “catch-up” program to vaccinate girls aged 13-21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model.

However, extending such a catch-up program to women older than 21 was not found to be a good value, the investigators said.

Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years.

In that case, continued screening and booster vaccines will be necessary and will add substantially to costs, Dr. Kim and Dr. Goldie commented.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs.

“How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861-2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted.

If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts.

The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys.

Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers stated that they did not have any potential conflicts of interest to report with regard to this study.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston.

They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained.

This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821-32).

Adding a “catch-up” program to vaccinate girls aged 13-21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model.

However, extending such a catch-up program to women older than 21 was not found to be a good value, the investigators said.

Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years.

In that case, continued screening and booster vaccines will be necessary and will add substantially to costs, Dr. Kim and Dr. Goldie commented.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs.

“How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861-2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted.

If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts.

The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys.

Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers stated that they did not have any potential conflicts of interest to report with regard to this study.

Human papillomavirus vaccination should be targeted at preadolescent girls, with initial “catch-up” programs aimed at women and girls aged younger than 21 years, but should not be directed at older women, according to a report.

The impact of the HPV vaccination will not be “observable for decades,” so decisions regarding vaccine policy must rely on estimates and mathematical simulation models, according to Jane J. Kim, Ph.D., and Dr. Sue J. Goldie of Harvard School of Public Health, Boston.

They devised such a model to examine possible outcomes of current HPV vaccination programs.

In creating this simulation model, the investigators took into consideration the cost-effectiveness of vaccinating various age groups as well as “the dynamics of HPV transmission, the duration of vaccine efficacy, the potential benefits of preventing noncervical HPV-related conditions, the anticipated changes in screening practice, and potential disparities in access to care.”

If it is assumed that the HPV vaccine confers lifelong immunity, the simulation model showed that routine vaccination of 12-year-old girls had a cost-effectiveness ratio of $43,600 per quality-adjusted life year gained.

This is well within the commonly cited threshold of good value for resources spent, which is $50,000-$100,000 per quality-adjusted life year gained, the investigators said (N. Engl. J. Med. 2008;359:821-32).

Adding a “catch-up” program to vaccinate girls aged 13-21 years also was found to be reasonably cost-effective, especially when the benefits of averting genital warts and of cross-protection against other high-risk types of HPV were added into the model.

However, extending such a catch-up program to women older than 21 was not found to be a good value, the investigators said.

Both the routine vaccination of 12-year-olds and the “catch-up” vaccination of adolescents remained cost-effective only at high levels of vaccine coverage, Dr. Kim and Dr. Goldie noted.

The model predicted less success for HPV vaccination programs if it turns out that immunity is not lifelong but lasts only 10 years.

In that case, continued screening and booster vaccines will be necessary and will add substantially to costs, Dr. Kim and Dr. Goldie commented.

In an editorial comment accompanying this report, Dr. Charlotte J. Haug, editor-in-chief of the Journal of the Norwegian Medical Association, Oslo, called the Harvard researchers' model “well done and ambitious.”

“There has been pressure on policy makers worldwide to introduce the HPV vaccine in national or statewide vaccination programs.

“How can policy makers make rational choices about the introduction of medical interventions that might do good in the future, but for which evidence is insufficient, especially since we will not know for many years whether the intervention will work or—in the worst case—do harm?” she asked (N. Engl. J. Med. 2008;359:861-2).

One answer is to “develop mathematical models of the natural history of the disease in question, introduce various intervention strategies, and use cost-effectiveness analysis to estimate the costs and health benefits associated with each clinical intervention,” as Dr. Kim and Dr. Goldie have done.

However, their model and its predictions are only as accurate as the assumptions on which the model is based, Dr. Haug noted.

If any of these assumptions turn out to be overly optimistic, then HPV vaccination will not turn out to be as successful as the model predicts.

The researchers cited other limitations in their analysis, saying that data on sexual behavior were primarily based on population averages from large surveys.

Also, data are limited on several factors: incidence; mortality and quality of life associated with noncervical HPV-related cancers; the long-term efficacy of the vaccine; and the efficacy of the vaccine against noncervical cancers.

The researchers stated that they did not have any potential conflicts of interest to report with regard to this study.

A family history of colon cancer raises the risk of developing the disease, but it also appears to be associated with a better prognosis, researchers reported.

Patients with stage III colon cancer who had a family history of the disease had significantly fewer recurrences and significantly better mortality 5 years after their diagnosis than did those with no family history of colon cancer in a study of over 1,000 patients.

This apparent benefit became stronger as the number of affected family members increased, said Dr. Jennifer A. Chan of the Dana-Farber Cancer Institute, Boston, and her associates. They assessed the influence of family history on survival using data on 1,087 patients with colon cancer who participated in a National Cancer Institute-sponsored clinical trial of adjuvant chemotherapy. All patients had undergone complete surgical resection of the primary tumor in 1999–2001, and all had regional lymph node metastases but no distant metastases at that time.

A total of 195 of the patients reported a family history of colon cancer in first-degree relatives. However, none had the hereditary colorectal cancer syndromes of familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer. After a mean of 5 years of follow-up, cancer recurrence or death occurred in 57 of these patients with a family history of the disease (29%), compared with 343 of the patients who did not have a family history (38%).

Cancer recurrence or death occurred in 30% of patients with one affected relative and in 23% of patients with two or more affected relatives, compared with 38% of those who had no affected relatives, the authors said (JAMA 2008;299:2515-23).

This protective effect persisted when the data were adjusted to account for numerous predictors of cancer recurrence and survival, including the possibility that patients with a family history may have had earlier tumor detection precisely because of this history. These patients all were subjects in a rigorously controlled, randomized clinical trial, so they all had the same disease stage, the same treatment and follow-up care, and the same extensive background data on possible confounding factors. The investigators noted that their findings “support the hypothesis that a relatively common … genetic predisposition may not only influence co-lorectal cancer risk but also patient survival.”

A family history of colon cancer raises the risk of developing the disease, but it also appears to be associated with a better prognosis, researchers reported.

Patients with stage III colon cancer who had a family history of the disease had significantly fewer recurrences and significantly better mortality 5 years after their diagnosis than did those with no family history of colon cancer in a study of over 1,000 patients.

This apparent benefit became stronger as the number of affected family members increased, said Dr. Jennifer A. Chan of the Dana-Farber Cancer Institute, Boston, and her associates. They assessed the influence of family history on survival using data on 1,087 patients with colon cancer who participated in a National Cancer Institute-sponsored clinical trial of adjuvant chemotherapy. All patients had undergone complete surgical resection of the primary tumor in 1999–2001, and all had regional lymph node metastases but no distant metastases at that time.

A total of 195 of the patients reported a family history of colon cancer in first-degree relatives. However, none had the hereditary colorectal cancer syndromes of familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer. After a mean of 5 years of follow-up, cancer recurrence or death occurred in 57 of these patients with a family history of the disease (29%), compared with 343 of the patients who did not have a family history (38%).

Cancer recurrence or death occurred in 30% of patients with one affected relative and in 23% of patients with two or more affected relatives, compared with 38% of those who had no affected relatives, the authors said (JAMA 2008;299:2515-23).

This protective effect persisted when the data were adjusted to account for numerous predictors of cancer recurrence and survival, including the possibility that patients with a family history may have had earlier tumor detection precisely because of this history. These patients all were subjects in a rigorously controlled, randomized clinical trial, so they all had the same disease stage, the same treatment and follow-up care, and the same extensive background data on possible confounding factors. The investigators noted that their findings “support the hypothesis that a relatively common … genetic predisposition may not only influence co-lorectal cancer risk but also patient survival.”

A family history of colon cancer raises the risk of developing the disease, but it also appears to be associated with a better prognosis, researchers reported.

Patients with stage III colon cancer who had a family history of the disease had significantly fewer recurrences and significantly better mortality 5 years after their diagnosis than did those with no family history of colon cancer in a study of over 1,000 patients.

This apparent benefit became stronger as the number of affected family members increased, said Dr. Jennifer A. Chan of the Dana-Farber Cancer Institute, Boston, and her associates. They assessed the influence of family history on survival using data on 1,087 patients with colon cancer who participated in a National Cancer Institute-sponsored clinical trial of adjuvant chemotherapy. All patients had undergone complete surgical resection of the primary tumor in 1999–2001, and all had regional lymph node metastases but no distant metastases at that time.

A total of 195 of the patients reported a family history of colon cancer in first-degree relatives. However, none had the hereditary colorectal cancer syndromes of familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer. After a mean of 5 years of follow-up, cancer recurrence or death occurred in 57 of these patients with a family history of the disease (29%), compared with 343 of the patients who did not have a family history (38%).

Cancer recurrence or death occurred in 30% of patients with one affected relative and in 23% of patients with two or more affected relatives, compared with 38% of those who had no affected relatives, the authors said (JAMA 2008;299:2515-23).

This protective effect persisted when the data were adjusted to account for numerous predictors of cancer recurrence and survival, including the possibility that patients with a family history may have had earlier tumor detection precisely because of this history. These patients all were subjects in a rigorously controlled, randomized clinical trial, so they all had the same disease stage, the same treatment and follow-up care, and the same extensive background data on possible confounding factors. The investigators noted that their findings “support the hypothesis that a relatively common … genetic predisposition may not only influence co-lorectal cancer risk but also patient survival.”

More women than men have sought tattoo removal in recent years, a reversal of the pattern that prevailed 10 years earlier, according to a report in the Archives of Dermatology.

Today, women report receiving significantly more negative comments and having more problems with "stigma" regarding their tattoos than do men. Women with tattoos are more likely to report embarrassment and "more societal fallout" than men with tattoos, according to Myrna L. Armstrong, Ed.D., of Texas Tech University Health Sciences Center, Marble Falls, and her associates.

The researchers studied the issue because "dermatologists are increasingly hearing stories of regrets and requests for tattoo removal. Estimated prevalence rates of dissatisfied tattoo wearers hover around 20%, with a smaller number who actually seek removal (6%)," they noted.

Dr. Armstrong and her colleagues assessed present-day tattoo removal using an anonymous survey of 196 clients aged 14–73 years who were attending four dermatology clinics in Arizona, Colorado, Massachusetts, and Texas. They compared the results with those from a similar survey conducted in 1996.

Although most of these subjects had been pleased with their tattoos when they first got them, they reported feeling dissatisfied with the tattoos for an average of 10 years before finally seeking removal. Most people who wanted to remove tattoos in 1996 were men, whereas most of those seeking removal in the present day were women, especially "career-minded" women.

Women reported receiving significantly more negative comments and suffering significantly more embarrassment regarding their tattoos than did men. In particular, women reported their tattoos interfered with their job or career and that they elicited negative comments in the workplace, in public, and in school settings, as wells as from significant others.

Currently, women also reported having to hide their tattoos with cosmetics or bandages and being unable to wear certain clothing because of their tattoos more often than men did. These findings correspond with reports in the literature that tattoo wearers are perceived as having lower credibility, competence, and sociability, particularly in the workplace, Dr. Armstrong and her associates said (Arch. Dermatol. 2008;144:879–84).

"For women, their tattoo procurement may be a way to break out of the gender norms and take some social risk by visually displaying their assertive identity. Yet, there still may be many members of society who consider tattoos on women to be a 'transgression of gender boundaries,'" the researchers wrote.

The major reason cited for getting a tattoo among both men and women who later sought removal was that it "helped me feel unique." Most of these subjects grew "disillusioned because their unique product had lost its luster and excitement." Some also said they were actively dissociating from their past or shifting their identity focus in order to "move on."

Dr. Armstrong is an education consultant for Freedom

More women than men have sought tattoo removal in recent years, a reversal of the pattern that prevailed 10 years earlier, according to a report in the Archives of Dermatology.

Today, women report receiving significantly more negative comments and having more problems with "stigma" regarding their tattoos than do men. Women with tattoos are more likely to report embarrassment and "more societal fallout" than men with tattoos, according to Myrna L. Armstrong, Ed.D., of Texas Tech University Health Sciences Center, Marble Falls, and her associates.

The researchers studied the issue because "dermatologists are increasingly hearing stories of regrets and requests for tattoo removal. Estimated prevalence rates of dissatisfied tattoo wearers hover around 20%, with a smaller number who actually seek removal (6%)," they noted.

Dr. Armstrong and her colleagues assessed present-day tattoo removal using an anonymous survey of 196 clients aged 14–73 years who were attending four dermatology clinics in Arizona, Colorado, Massachusetts, and Texas. They compared the results with those from a similar survey conducted in 1996.

Although most of these subjects had been pleased with their tattoos when they first got them, they reported feeling dissatisfied with the tattoos for an average of 10 years before finally seeking removal. Most people who wanted to remove tattoos in 1996 were men, whereas most of those seeking removal in the present day were women, especially "career-minded" women.

Women reported receiving significantly more negative comments and suffering significantly more embarrassment regarding their tattoos than did men. In particular, women reported their tattoos interfered with their job or career and that they elicited negative comments in the workplace, in public, and in school settings, as wells as from significant others.

Currently, women also reported having to hide their tattoos with cosmetics or bandages and being unable to wear certain clothing because of their tattoos more often than men did. These findings correspond with reports in the literature that tattoo wearers are perceived as having lower credibility, competence, and sociability, particularly in the workplace, Dr. Armstrong and her associates said (Arch. Dermatol. 2008;144:879–84).

"For women, their tattoo procurement may be a way to break out of the gender norms and take some social risk by visually displaying their assertive identity. Yet, there still may be many members of society who consider tattoos on women to be a 'transgression of gender boundaries,'" the researchers wrote.

The major reason cited for getting a tattoo among both men and women who later sought removal was that it "helped me feel unique." Most of these subjects grew "disillusioned because their unique product had lost its luster and excitement." Some also said they were actively dissociating from their past or shifting their identity focus in order to "move on."

Dr. Armstrong is an education consultant for Freedom

More women than men have sought tattoo removal in recent years, a reversal of the pattern that prevailed 10 years earlier, according to a report in the Archives of Dermatology.

Today, women report receiving significantly more negative comments and having more problems with "stigma" regarding their tattoos than do men. Women with tattoos are more likely to report embarrassment and "more societal fallout" than men with tattoos, according to Myrna L. Armstrong, Ed.D., of Texas Tech University Health Sciences Center, Marble Falls, and her associates.

The researchers studied the issue because "dermatologists are increasingly hearing stories of regrets and requests for tattoo removal. Estimated prevalence rates of dissatisfied tattoo wearers hover around 20%, with a smaller number who actually seek removal (6%)," they noted.

Dr. Armstrong and her colleagues assessed present-day tattoo removal using an anonymous survey of 196 clients aged 14–73 years who were attending four dermatology clinics in Arizona, Colorado, Massachusetts, and Texas. They compared the results with those from a similar survey conducted in 1996.

Although most of these subjects had been pleased with their tattoos when they first got them, they reported feeling dissatisfied with the tattoos for an average of 10 years before finally seeking removal. Most people who wanted to remove tattoos in 1996 were men, whereas most of those seeking removal in the present day were women, especially "career-minded" women.

Women reported receiving significantly more negative comments and suffering significantly more embarrassment regarding their tattoos than did men. In particular, women reported their tattoos interfered with their job or career and that they elicited negative comments in the workplace, in public, and in school settings, as wells as from significant others.

Currently, women also reported having to hide their tattoos with cosmetics or bandages and being unable to wear certain clothing because of their tattoos more often than men did. These findings correspond with reports in the literature that tattoo wearers are perceived as having lower credibility, competence, and sociability, particularly in the workplace, Dr. Armstrong and her associates said (Arch. Dermatol. 2008;144:879–84).

"For women, their tattoo procurement may be a way to break out of the gender norms and take some social risk by visually displaying their assertive identity. Yet, there still may be many members of society who consider tattoos on women to be a 'transgression of gender boundaries,'" the researchers wrote.

The major reason cited for getting a tattoo among both men and women who later sought removal was that it "helped me feel unique." Most of these subjects grew "disillusioned because their unique product had lost its luster and excitement." Some also said they were actively dissociating from their past or shifting their identity focus in order to "move on."

Dr. Armstrong is an education consultant for Freedom