Jennie Smith

Findings from a large international prospective study reveal that only about half of people with known cardiovascular disease or previous stroke worldwide take any effective medication, even so much as aspirin, to prevent future events.

In the poorest countries studied, fewer than one-fifth were on medication.

The study revealed what investigators described as global underuse of preventive medications, and "striking variations" in prevalence of preventive drug use, with the economic status of countries accounting for most of the variation seen.

Even the use of cheap and widely available aspirin, the most commonly used antiplatelet drug in the world, varied sevenfold between low-income and high-income countries. Use of statins was seen as varying 20-fold, with almost no use in Africa, and very little in South Asia.

For their research, published Aug. 28 in the Lancet (doi:10.1016/S0140-6736[11]61215-4), Dr. Salim Yusuf of Hamilton Health Sciences and McMaster University in Hamilton, Ontario, and his colleagues, looked at use of antiplatelet drugs, beta-blockers, ACE inhibitors, angiotensin-receptor blockers, and statins in an epidemiologic cohort of 153,996 people aged 35-70 years in 17 countries during 2003-2009. More than half (56%) of participants were women.

Of the study subjects, 5,650 reported having a prior coronary heart disease event, and 2,292 reported prior stroke. The likelihood of these subjects being on any of the four effective drug types had mostly to do with the economic status of their country of residence, Dr. Yusuf and his colleagues found.

Individual-level factors, such as age, sex, education, smoking, body-mass index, and hypertension or diabetes status, accounted for about a third of the variation, while country income accounted for the rest. In all settings, fewer women than men took the drugs, although Dr. Yusuf and his colleagues described no clear reason why. Urban or rural residency was not seen as accounting for as much variation after researchers adjusted for other factors.

While all but 11% of people who needed preventive drugs received them in high-income countries such as Canada and Sweden, 45% of those living in upper–middle-income countries such as Poland were not receiving any preventive drugs.

In lower–middle-income countries such as Colombia, 69% of patients in need were unmedicated. In the lowest-income countries studied, the share of unmedicated people was seen as higher than 80%, and higher still in Africa.

Overall, antiplatelet drugs were taken by only 25% of study subjects, beta-blockers by 17%, ACE inhibitors or ARBs by 20%, and statins by 15%.

However, use of specific drug types also varied widely by region, with only 1% of Africans and 2% of Chinese taking statins, compared with 52% of North Americans and Europeans.

Use of preventive drug therapy was far from ideal, even in the high-income countries studied, the authors found, noting that in Canada, Sweden, and the United Arab Emirates as a group, only 61% of patients who had had a stroke received a blood-pressure–lowering drug.

Dr. Yusuf and his colleagues’ research was supported by grants from a number of pharmaceutical firms, including AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GlaxoSmithKline, Novartis, and King Pharma. The researchers described as a limitation of their study the fact that it relied on self-reporting of cardiovascular events and stroke.

In an editorial comment (doi:10.1016/S0140-6736[11]61302-0) accompanying the researchers’ study, Dr. Anthony M. Heagerty of the Cardiovascular Research Group at the University of Manchester (England) described the findings as containing a "stark and alarming message" about underuse worldwide.

The results are "especially disappointing" in the high-income countries, Dr. Heagerty wrote, "where well-developed health care provision should ensure the implementation of best practice and any concerns about optimum data gathering will be small." Dr. Heagerty ascribed some of the underprescribing to "fears about polypharmacy" and a focus on reduction of risk factors instead of risks to the individual patient."

Dr. Heagerty disclosed having received consulting and speaking fees from Servier, Merck Serono, Novartis, and DaiichiSankyo.

Findings from a large international prospective study reveal that only about half of people with known cardiovascular disease or previous stroke worldwide take any effective medication, even so much as aspirin, to prevent future events.

In the poorest countries studied, fewer than one-fifth were on medication.

The study revealed what investigators described as global underuse of preventive medications, and "striking variations" in prevalence of preventive drug use, with the economic status of countries accounting for most of the variation seen.

Even the use of cheap and widely available aspirin, the most commonly used antiplatelet drug in the world, varied sevenfold between low-income and high-income countries. Use of statins was seen as varying 20-fold, with almost no use in Africa, and very little in South Asia.

For their research, published Aug. 28 in the Lancet (doi:10.1016/S0140-6736[11]61215-4), Dr. Salim Yusuf of Hamilton Health Sciences and McMaster University in Hamilton, Ontario, and his colleagues, looked at use of antiplatelet drugs, beta-blockers, ACE inhibitors, angiotensin-receptor blockers, and statins in an epidemiologic cohort of 153,996 people aged 35-70 years in 17 countries during 2003-2009. More than half (56%) of participants were women.

Of the study subjects, 5,650 reported having a prior coronary heart disease event, and 2,292 reported prior stroke. The likelihood of these subjects being on any of the four effective drug types had mostly to do with the economic status of their country of residence, Dr. Yusuf and his colleagues found.

Individual-level factors, such as age, sex, education, smoking, body-mass index, and hypertension or diabetes status, accounted for about a third of the variation, while country income accounted for the rest. In all settings, fewer women than men took the drugs, although Dr. Yusuf and his colleagues described no clear reason why. Urban or rural residency was not seen as accounting for as much variation after researchers adjusted for other factors.

While all but 11% of people who needed preventive drugs received them in high-income countries such as Canada and Sweden, 45% of those living in upper–middle-income countries such as Poland were not receiving any preventive drugs.

In lower–middle-income countries such as Colombia, 69% of patients in need were unmedicated. In the lowest-income countries studied, the share of unmedicated people was seen as higher than 80%, and higher still in Africa.

Overall, antiplatelet drugs were taken by only 25% of study subjects, beta-blockers by 17%, ACE inhibitors or ARBs by 20%, and statins by 15%.

However, use of specific drug types also varied widely by region, with only 1% of Africans and 2% of Chinese taking statins, compared with 52% of North Americans and Europeans.

Use of preventive drug therapy was far from ideal, even in the high-income countries studied, the authors found, noting that in Canada, Sweden, and the United Arab Emirates as a group, only 61% of patients who had had a stroke received a blood-pressure–lowering drug.

Dr. Yusuf and his colleagues’ research was supported by grants from a number of pharmaceutical firms, including AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GlaxoSmithKline, Novartis, and King Pharma. The researchers described as a limitation of their study the fact that it relied on self-reporting of cardiovascular events and stroke.

In an editorial comment (doi:10.1016/S0140-6736[11]61302-0) accompanying the researchers’ study, Dr. Anthony M. Heagerty of the Cardiovascular Research Group at the University of Manchester (England) described the findings as containing a "stark and alarming message" about underuse worldwide.

The results are "especially disappointing" in the high-income countries, Dr. Heagerty wrote, "where well-developed health care provision should ensure the implementation of best practice and any concerns about optimum data gathering will be small." Dr. Heagerty ascribed some of the underprescribing to "fears about polypharmacy" and a focus on reduction of risk factors instead of risks to the individual patient."

Dr. Heagerty disclosed having received consulting and speaking fees from Servier, Merck Serono, Novartis, and DaiichiSankyo.

Findings from a large international prospective study reveal that only about half of people with known cardiovascular disease or previous stroke worldwide take any effective medication, even so much as aspirin, to prevent future events.

In the poorest countries studied, fewer than one-fifth were on medication.

The study revealed what investigators described as global underuse of preventive medications, and "striking variations" in prevalence of preventive drug use, with the economic status of countries accounting for most of the variation seen.

Even the use of cheap and widely available aspirin, the most commonly used antiplatelet drug in the world, varied sevenfold between low-income and high-income countries. Use of statins was seen as varying 20-fold, with almost no use in Africa, and very little in South Asia.

For their research, published Aug. 28 in the Lancet (doi:10.1016/S0140-6736[11]61215-4), Dr. Salim Yusuf of Hamilton Health Sciences and McMaster University in Hamilton, Ontario, and his colleagues, looked at use of antiplatelet drugs, beta-blockers, ACE inhibitors, angiotensin-receptor blockers, and statins in an epidemiologic cohort of 153,996 people aged 35-70 years in 17 countries during 2003-2009. More than half (56%) of participants were women.

Of the study subjects, 5,650 reported having a prior coronary heart disease event, and 2,292 reported prior stroke. The likelihood of these subjects being on any of the four effective drug types had mostly to do with the economic status of their country of residence, Dr. Yusuf and his colleagues found.

Individual-level factors, such as age, sex, education, smoking, body-mass index, and hypertension or diabetes status, accounted for about a third of the variation, while country income accounted for the rest. In all settings, fewer women than men took the drugs, although Dr. Yusuf and his colleagues described no clear reason why. Urban or rural residency was not seen as accounting for as much variation after researchers adjusted for other factors.

While all but 11% of people who needed preventive drugs received them in high-income countries such as Canada and Sweden, 45% of those living in upper–middle-income countries such as Poland were not receiving any preventive drugs.

In lower–middle-income countries such as Colombia, 69% of patients in need were unmedicated. In the lowest-income countries studied, the share of unmedicated people was seen as higher than 80%, and higher still in Africa.

Overall, antiplatelet drugs were taken by only 25% of study subjects, beta-blockers by 17%, ACE inhibitors or ARBs by 20%, and statins by 15%.

However, use of specific drug types also varied widely by region, with only 1% of Africans and 2% of Chinese taking statins, compared with 52% of North Americans and Europeans.

Use of preventive drug therapy was far from ideal, even in the high-income countries studied, the authors found, noting that in Canada, Sweden, and the United Arab Emirates as a group, only 61% of patients who had had a stroke received a blood-pressure–lowering drug.

Dr. Yusuf and his colleagues’ research was supported by grants from a number of pharmaceutical firms, including AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GlaxoSmithKline, Novartis, and King Pharma. The researchers described as a limitation of their study the fact that it relied on self-reporting of cardiovascular events and stroke.

In an editorial comment (doi:10.1016/S0140-6736[11]61302-0) accompanying the researchers’ study, Dr. Anthony M. Heagerty of the Cardiovascular Research Group at the University of Manchester (England) described the findings as containing a "stark and alarming message" about underuse worldwide.

The results are "especially disappointing" in the high-income countries, Dr. Heagerty wrote, "where well-developed health care provision should ensure the implementation of best practice and any concerns about optimum data gathering will be small." Dr. Heagerty ascribed some of the underprescribing to "fears about polypharmacy" and a focus on reduction of risk factors instead of risks to the individual patient."

Dr. Heagerty disclosed having received consulting and speaking fees from Servier, Merck Serono, Novartis, and DaiichiSankyo.

Women seeking genital surgery to reduce the size of their labia minora do not have large or misshapen labia, and also tend to be relatively young, a small U.K. study has found.

Of the 33 women in the prospective study, published Aug. 24 in BJOG, 30 had labia with dimensions within the normal published limits, yet sought surgery anyway. The women’s average age was 23 years, although a quarter were 16 years or younger, with the youngest being 11 years old.

This points to the psychological or cultural appeal of cosmetic genital surgery among young women and girls, the study’s authors say, which may be influenced by grooming trends that expose the vulva – two-thirds of women in the study had removed their pubic hair – and by widespread advertising of the surgical procedures using before-and-after photos, which about one-third of subjects reported having consulted (BJOG 2011 Aug. 24 [doi:10.1111/j.1471-0528.2011.03088.x]).

"We noticed that more young women were coming in saying, ‘we’re not normal,’ " said Dr. Sarah Creighton, a gynecologist at University College London’s Elizabeth Garrett Anderson Institute of Women’s Health and the corresponding author of the study, in an interview. "And yet there is little information about what is normal."

For their research, Dr. Creighton and colleagues at a London hospital clinic (which performs the surgeries on women whose genitalia are outside normal measures) interviewed women referred to them by primary care physicians. Two-thirds of the women seeking surgery identified themselves as students, only 15% had given birth, and two-thirds reported being single. Most (84%) were white.

The women did not appear to be guided by sexual concerns, as a majority (61%) reported having never been sexually active.

Dr. Creighton and colleagues interviewed the women on their reasons for seeking surgery, and found that most (78%) were motivated by concerns about the appearance of their genitals. Although discomfort, such as that caused by rubbing or chafing, was reported by 57% of them, only 18% said that they thought surgery would help.

The investigators also measured the women’s labia, finding all but three to be within normal published limits, with a mean (SD) of 26.9 (12.8) mm on the right side, and 24.8 (13.1) mm on the left. Surgeries were offered only to those women whose labia were outside that range.

The investigators were surprised, they wrote, to find "that all of the study participants and their referring doctors should have felt that surgery was an appropriate treatment," when the women’s labia were normal. Moreover, 40% of the 30 participants who were denied surgery by the clinic "remained keen to pursue surgery by any other available route."

About 2,000 women now receive the surgeries every year through NHS clinics, a fivefold increase from a decade ago, Dr. Creighton and colleagues noted, with privately performed procedures likely accounting for a far greater number. Yet despite the expanding availability of the procedure, a U.K. law prohibits female genital surgeries for cultural or nontherapeutic reasons, even on adult women.

Thus far, Dr. Creighton said, no lawsuit has challenged the legality of the procedure, which some NHS trusts offer on the grounds of alleviating psychological distress.

"There are no guidelines. The NHS is not publicly discussing it," Dr. Creighton said, adding that professional surgical associations have not issued clear guidelines for treating women seeking labial surgery, leaving clinician discretion as the norm.

"National care standards are urgently needed," Dr. Creighton and colleagues wrote in their analysis. The investigators also urged the publication of data on normal labial measurements "based on a large adult general population sample stratified according to age, ethnicity and parity."

The study was funded by the Elizabeth Garrett Anderson Institute of Women’s Health at University College London. None of its authors declared conflicts of interest.

Women seeking genital surgery to reduce the size of their labia minora do not have large or misshapen labia, and also tend to be relatively young, a small U.K. study has found.

Of the 33 women in the prospective study, published Aug. 24 in BJOG, 30 had labia with dimensions within the normal published limits, yet sought surgery anyway. The women’s average age was 23 years, although a quarter were 16 years or younger, with the youngest being 11 years old.

This points to the psychological or cultural appeal of cosmetic genital surgery among young women and girls, the study’s authors say, which may be influenced by grooming trends that expose the vulva – two-thirds of women in the study had removed their pubic hair – and by widespread advertising of the surgical procedures using before-and-after photos, which about one-third of subjects reported having consulted (BJOG 2011 Aug. 24 [doi:10.1111/j.1471-0528.2011.03088.x]).

"We noticed that more young women were coming in saying, ‘we’re not normal,’ " said Dr. Sarah Creighton, a gynecologist at University College London’s Elizabeth Garrett Anderson Institute of Women’s Health and the corresponding author of the study, in an interview. "And yet there is little information about what is normal."

For their research, Dr. Creighton and colleagues at a London hospital clinic (which performs the surgeries on women whose genitalia are outside normal measures) interviewed women referred to them by primary care physicians. Two-thirds of the women seeking surgery identified themselves as students, only 15% had given birth, and two-thirds reported being single. Most (84%) were white.

The women did not appear to be guided by sexual concerns, as a majority (61%) reported having never been sexually active.

Dr. Creighton and colleagues interviewed the women on their reasons for seeking surgery, and found that most (78%) were motivated by concerns about the appearance of their genitals. Although discomfort, such as that caused by rubbing or chafing, was reported by 57% of them, only 18% said that they thought surgery would help.

The investigators also measured the women’s labia, finding all but three to be within normal published limits, with a mean (SD) of 26.9 (12.8) mm on the right side, and 24.8 (13.1) mm on the left. Surgeries were offered only to those women whose labia were outside that range.

The investigators were surprised, they wrote, to find "that all of the study participants and their referring doctors should have felt that surgery was an appropriate treatment," when the women’s labia were normal. Moreover, 40% of the 30 participants who were denied surgery by the clinic "remained keen to pursue surgery by any other available route."

About 2,000 women now receive the surgeries every year through NHS clinics, a fivefold increase from a decade ago, Dr. Creighton and colleagues noted, with privately performed procedures likely accounting for a far greater number. Yet despite the expanding availability of the procedure, a U.K. law prohibits female genital surgeries for cultural or nontherapeutic reasons, even on adult women.

Thus far, Dr. Creighton said, no lawsuit has challenged the legality of the procedure, which some NHS trusts offer on the grounds of alleviating psychological distress.

"There are no guidelines. The NHS is not publicly discussing it," Dr. Creighton said, adding that professional surgical associations have not issued clear guidelines for treating women seeking labial surgery, leaving clinician discretion as the norm.

"National care standards are urgently needed," Dr. Creighton and colleagues wrote in their analysis. The investigators also urged the publication of data on normal labial measurements "based on a large adult general population sample stratified according to age, ethnicity and parity."

The study was funded by the Elizabeth Garrett Anderson Institute of Women’s Health at University College London. None of its authors declared conflicts of interest.

Women seeking genital surgery to reduce the size of their labia minora do not have large or misshapen labia, and also tend to be relatively young, a small U.K. study has found.

Of the 33 women in the prospective study, published Aug. 24 in BJOG, 30 had labia with dimensions within the normal published limits, yet sought surgery anyway. The women’s average age was 23 years, although a quarter were 16 years or younger, with the youngest being 11 years old.

This points to the psychological or cultural appeal of cosmetic genital surgery among young women and girls, the study’s authors say, which may be influenced by grooming trends that expose the vulva – two-thirds of women in the study had removed their pubic hair – and by widespread advertising of the surgical procedures using before-and-after photos, which about one-third of subjects reported having consulted (BJOG 2011 Aug. 24 [doi:10.1111/j.1471-0528.2011.03088.x]).

"We noticed that more young women were coming in saying, ‘we’re not normal,’ " said Dr. Sarah Creighton, a gynecologist at University College London’s Elizabeth Garrett Anderson Institute of Women’s Health and the corresponding author of the study, in an interview. "And yet there is little information about what is normal."

For their research, Dr. Creighton and colleagues at a London hospital clinic (which performs the surgeries on women whose genitalia are outside normal measures) interviewed women referred to them by primary care physicians. Two-thirds of the women seeking surgery identified themselves as students, only 15% had given birth, and two-thirds reported being single. Most (84%) were white.

The women did not appear to be guided by sexual concerns, as a majority (61%) reported having never been sexually active.

Dr. Creighton and colleagues interviewed the women on their reasons for seeking surgery, and found that most (78%) were motivated by concerns about the appearance of their genitals. Although discomfort, such as that caused by rubbing or chafing, was reported by 57% of them, only 18% said that they thought surgery would help.

The investigators also measured the women’s labia, finding all but three to be within normal published limits, with a mean (SD) of 26.9 (12.8) mm on the right side, and 24.8 (13.1) mm on the left. Surgeries were offered only to those women whose labia were outside that range.

The investigators were surprised, they wrote, to find "that all of the study participants and their referring doctors should have felt that surgery was an appropriate treatment," when the women’s labia were normal. Moreover, 40% of the 30 participants who were denied surgery by the clinic "remained keen to pursue surgery by any other available route."

About 2,000 women now receive the surgeries every year through NHS clinics, a fivefold increase from a decade ago, Dr. Creighton and colleagues noted, with privately performed procedures likely accounting for a far greater number. Yet despite the expanding availability of the procedure, a U.K. law prohibits female genital surgeries for cultural or nontherapeutic reasons, even on adult women.

Thus far, Dr. Creighton said, no lawsuit has challenged the legality of the procedure, which some NHS trusts offer on the grounds of alleviating psychological distress.

"There are no guidelines. The NHS is not publicly discussing it," Dr. Creighton said, adding that professional surgical associations have not issued clear guidelines for treating women seeking labial surgery, leaving clinician discretion as the norm.

"National care standards are urgently needed," Dr. Creighton and colleagues wrote in their analysis. The investigators also urged the publication of data on normal labial measurements "based on a large adult general population sample stratified according to age, ethnicity and parity."

The study was funded by the Elizabeth Garrett Anderson Institute of Women’s Health at University College London. None of its authors declared conflicts of interest.

An independent committee of experts that develops guidance on behalf of the U.K. National Institute for Health and Clinical Excellence does not believe that fulvestrant, which can be used to delay the growth of a particular type of advanced breast cancer, represents a good use of National Health Service resources.

Draft guidance, published Aug. 22 for public comment, does not recommend fulvestrant (known commercially as Faslodex and manufactured by AstraZeneca) as an alternative to aromatase inhibitor therapy in postmenopausal women who have locally advanced or metastatic breast cancer that is estrogen-receptor positive.

In accordance with its marketing authorization, the committee’s provisional recommendation relates to the use of fulvestrant once antiestrogen treatments (such as tamoxifen) are no longer controlling the spread of the cancer. The committee has not been able to consider the clinical and cost effectiveness of fulvestrant when it is used outside of its marketing authorization (for example, after an aromatase inhibitor).

Sir Andrew Dillon, chief executive of NICE, said in a written statement that "while it is important for women with locally advanced or metastatic breast cancer to have a range of options, NICE has to ensure that the NHS provides treatments that bring benefits which are value for money.

"After analysing the evidence comparing fulvestrant’s clinical effectiveness with aromatase inhibitor therapy, our independent committee found that the estimates of overall survival and time to tumour progression were very uncertain. The Committee concluded that it had not been given any conclusive evidence that fulvestrant extends life or delays tumour progression any more than aromatase inhibitor therapy, which is currently used in the NHS."

NICE’s final guidance will determine whether the NHS is legally obliged to allocate funding for fulvestrant as an alternative to aromatase inhibitors for the treatment of locally advanced or metastatic breast cancer after antiestrogen treatment. Until NICE issues final guidance, these decisions should continue to be made locally by NHS bodies.

Those wishing to comment on NICE’s draft recommendations have until Sept. 13 to do so. NICE’s independent committee will then meet again to review the comments received. NICE expects to publish its final guidance for the NHS in January 2012.

An independent committee of experts that develops guidance on behalf of the U.K. National Institute for Health and Clinical Excellence does not believe that fulvestrant, which can be used to delay the growth of a particular type of advanced breast cancer, represents a good use of National Health Service resources.

Draft guidance, published Aug. 22 for public comment, does not recommend fulvestrant (known commercially as Faslodex and manufactured by AstraZeneca) as an alternative to aromatase inhibitor therapy in postmenopausal women who have locally advanced or metastatic breast cancer that is estrogen-receptor positive.

In accordance with its marketing authorization, the committee’s provisional recommendation relates to the use of fulvestrant once antiestrogen treatments (such as tamoxifen) are no longer controlling the spread of the cancer. The committee has not been able to consider the clinical and cost effectiveness of fulvestrant when it is used outside of its marketing authorization (for example, after an aromatase inhibitor).

Sir Andrew Dillon, chief executive of NICE, said in a written statement that "while it is important for women with locally advanced or metastatic breast cancer to have a range of options, NICE has to ensure that the NHS provides treatments that bring benefits which are value for money.

"After analysing the evidence comparing fulvestrant’s clinical effectiveness with aromatase inhibitor therapy, our independent committee found that the estimates of overall survival and time to tumour progression were very uncertain. The Committee concluded that it had not been given any conclusive evidence that fulvestrant extends life or delays tumour progression any more than aromatase inhibitor therapy, which is currently used in the NHS."

NICE’s final guidance will determine whether the NHS is legally obliged to allocate funding for fulvestrant as an alternative to aromatase inhibitors for the treatment of locally advanced or metastatic breast cancer after antiestrogen treatment. Until NICE issues final guidance, these decisions should continue to be made locally by NHS bodies.

Those wishing to comment on NICE’s draft recommendations have until Sept. 13 to do so. NICE’s independent committee will then meet again to review the comments received. NICE expects to publish its final guidance for the NHS in January 2012.

An independent committee of experts that develops guidance on behalf of the U.K. National Institute for Health and Clinical Excellence does not believe that fulvestrant, which can be used to delay the growth of a particular type of advanced breast cancer, represents a good use of National Health Service resources.

Draft guidance, published Aug. 22 for public comment, does not recommend fulvestrant (known commercially as Faslodex and manufactured by AstraZeneca) as an alternative to aromatase inhibitor therapy in postmenopausal women who have locally advanced or metastatic breast cancer that is estrogen-receptor positive.

In accordance with its marketing authorization, the committee’s provisional recommendation relates to the use of fulvestrant once antiestrogen treatments (such as tamoxifen) are no longer controlling the spread of the cancer. The committee has not been able to consider the clinical and cost effectiveness of fulvestrant when it is used outside of its marketing authorization (for example, after an aromatase inhibitor).

Sir Andrew Dillon, chief executive of NICE, said in a written statement that "while it is important for women with locally advanced or metastatic breast cancer to have a range of options, NICE has to ensure that the NHS provides treatments that bring benefits which are value for money.

"After analysing the evidence comparing fulvestrant’s clinical effectiveness with aromatase inhibitor therapy, our independent committee found that the estimates of overall survival and time to tumour progression were very uncertain. The Committee concluded that it had not been given any conclusive evidence that fulvestrant extends life or delays tumour progression any more than aromatase inhibitor therapy, which is currently used in the NHS."

NICE’s final guidance will determine whether the NHS is legally obliged to allocate funding for fulvestrant as an alternative to aromatase inhibitors for the treatment of locally advanced or metastatic breast cancer after antiestrogen treatment. Until NICE issues final guidance, these decisions should continue to be made locally by NHS bodies.

Those wishing to comment on NICE’s draft recommendations have until Sept. 13 to do so. NICE’s independent committee will then meet again to review the comments received. NICE expects to publish its final guidance for the NHS in January 2012.

Multiple tests are needed to detect intestinal parasite infections in children who were adopted from overseas – including children without gastrointestinal symptoms – according to a new study in the August issue of Pediatrics.

The study enrolled 1,042 children within 120 days of their arrival in the United States from 36 countries in Asia, Europe, Latin America, and Africa.

Of these, 27% were found to be infected with intestinal parasites (most commonly Giardia intestinalis), a rate higher than that seen in previous studies of internationally adopted children. Prevalence of infection was associated with increasing age at adoption, birth country, and history of institutionalization, but not with gastrointestinal symptoms (Pediatrics 2011 Aug. 8 [doi:10.1542/peds.2010-3032]).

Although 40% of children aged older than 1 year had a pathogen compared with 7% of those who were younger, and 34% institutionalized children had a pathogen compared with only 4% of noninstitutionalized children, the proportion of infections was the same among both the children whose parents reported diarrhea or more than three stools per day and those whose parents reported no such symptoms.

Current screening guidelines from the American Academy of Pediatrics’ online Red Book recommend that three stool samples be tested in recently adopted children who have gastrointestinal symptoms. Only one sample is deemed necessary for asymptomatic children.

However, the researchers, led by Dr. Mary Allen Staat of Cincinnati Children’s Hospital Medical Center, found that multiple tests significantly increased the likelihood of pathogen detection in children, whether or not they had symptoms. If a single stool sample was tested, the probability of identifying a pathogen was 79%. With two samples, the probability significantly increased to 92%, and for three, it was 100%.

This suggests, Dr. Staat and colleagues wrote, that the current American Academy of Pediatrics’ guidelines should be revised so that three stool specimens, taken 48-72 hours apart, "are submitted and evaluated for all internationally adopted children on arrival to the United States, regardless of gastrointestinal symptoms."

Dr. Elaine Schulte, chair of pediatrics at the Cleveland Clinic and medical director of its international adoption program, said in an interview that the findings had "important" implications for pediatricians and families of internationally adopted children. (The Cleveland Clinic’s international adoption program provides comprehensive medical care to internationally adopted children, including preadoption and postadoption consultation and ongoing care.)

"You can’t rely on kids to be symptomatic," Dr. Schulte said. "For physicians who see internationally adopted kids – but not very many – they may rely on parent assessment, which is not good. Most parents who are adopting internationally have heard about parasites, [but] that doesn’t mean they know what they are, or understand the process of detecting them."

Undiagnosed, untreated parasite infections can lead to malnutrition, and also can be contagious in school and family settings, Dr. Schulte noted. "I’ve taken care of lots of kids who just pass it back and forth among siblings, and it’s really hard to get rid of. Parents also can get infected."

Dr. Staat and her colleagues found the lowest infection rates among children born in South Korea (0%), followed by Guatemala (9%), China (13%), and Vietnam (19%). The highest rates were seen in children from Romania (50%), Bulgaria (54%), Ethiopia (55%), and the Ukraine (74%).

In addition to G. intestinalis, which was present in 19% of children in the study, identified pathogens included Blastocystis hominis (10% of children), Dientamoeba fragilis (5%), and Entamoeba histolytica (1%). Helminths (parasitic worms) were found in 2% of children.

Dr. Staat and her colleagues declared that they had no relevant financial disclosures. Dr. Schulte said that she had no relevant financial disclosures.

Multiple tests are needed to detect intestinal parasite infections in children who were adopted from overseas – including children without gastrointestinal symptoms – according to a new study in the August issue of Pediatrics.

The study enrolled 1,042 children within 120 days of their arrival in the United States from 36 countries in Asia, Europe, Latin America, and Africa.

Of these, 27% were found to be infected with intestinal parasites (most commonly Giardia intestinalis), a rate higher than that seen in previous studies of internationally adopted children. Prevalence of infection was associated with increasing age at adoption, birth country, and history of institutionalization, but not with gastrointestinal symptoms (Pediatrics 2011 Aug. 8 [doi:10.1542/peds.2010-3032]).

Although 40% of children aged older than 1 year had a pathogen compared with 7% of those who were younger, and 34% institutionalized children had a pathogen compared with only 4% of noninstitutionalized children, the proportion of infections was the same among both the children whose parents reported diarrhea or more than three stools per day and those whose parents reported no such symptoms.

Current screening guidelines from the American Academy of Pediatrics’ online Red Book recommend that three stool samples be tested in recently adopted children who have gastrointestinal symptoms. Only one sample is deemed necessary for asymptomatic children.

However, the researchers, led by Dr. Mary Allen Staat of Cincinnati Children’s Hospital Medical Center, found that multiple tests significantly increased the likelihood of pathogen detection in children, whether or not they had symptoms. If a single stool sample was tested, the probability of identifying a pathogen was 79%. With two samples, the probability significantly increased to 92%, and for three, it was 100%.

This suggests, Dr. Staat and colleagues wrote, that the current American Academy of Pediatrics’ guidelines should be revised so that three stool specimens, taken 48-72 hours apart, "are submitted and evaluated for all internationally adopted children on arrival to the United States, regardless of gastrointestinal symptoms."

Dr. Elaine Schulte, chair of pediatrics at the Cleveland Clinic and medical director of its international adoption program, said in an interview that the findings had "important" implications for pediatricians and families of internationally adopted children. (The Cleveland Clinic’s international adoption program provides comprehensive medical care to internationally adopted children, including preadoption and postadoption consultation and ongoing care.)

"You can’t rely on kids to be symptomatic," Dr. Schulte said. "For physicians who see internationally adopted kids – but not very many – they may rely on parent assessment, which is not good. Most parents who are adopting internationally have heard about parasites, [but] that doesn’t mean they know what they are, or understand the process of detecting them."

Undiagnosed, untreated parasite infections can lead to malnutrition, and also can be contagious in school and family settings, Dr. Schulte noted. "I’ve taken care of lots of kids who just pass it back and forth among siblings, and it’s really hard to get rid of. Parents also can get infected."

Dr. Staat and her colleagues found the lowest infection rates among children born in South Korea (0%), followed by Guatemala (9%), China (13%), and Vietnam (19%). The highest rates were seen in children from Romania (50%), Bulgaria (54%), Ethiopia (55%), and the Ukraine (74%).

In addition to G. intestinalis, which was present in 19% of children in the study, identified pathogens included Blastocystis hominis (10% of children), Dientamoeba fragilis (5%), and Entamoeba histolytica (1%). Helminths (parasitic worms) were found in 2% of children.

Dr. Staat and her colleagues declared that they had no relevant financial disclosures. Dr. Schulte said that she had no relevant financial disclosures.

Multiple tests are needed to detect intestinal parasite infections in children who were adopted from overseas – including children without gastrointestinal symptoms – according to a new study in the August issue of Pediatrics.

The study enrolled 1,042 children within 120 days of their arrival in the United States from 36 countries in Asia, Europe, Latin America, and Africa.

Of these, 27% were found to be infected with intestinal parasites (most commonly Giardia intestinalis), a rate higher than that seen in previous studies of internationally adopted children. Prevalence of infection was associated with increasing age at adoption, birth country, and history of institutionalization, but not with gastrointestinal symptoms (Pediatrics 2011 Aug. 8 [doi:10.1542/peds.2010-3032]).

Although 40% of children aged older than 1 year had a pathogen compared with 7% of those who were younger, and 34% institutionalized children had a pathogen compared with only 4% of noninstitutionalized children, the proportion of infections was the same among both the children whose parents reported diarrhea or more than three stools per day and those whose parents reported no such symptoms.

Current screening guidelines from the American Academy of Pediatrics’ online Red Book recommend that three stool samples be tested in recently adopted children who have gastrointestinal symptoms. Only one sample is deemed necessary for asymptomatic children.

However, the researchers, led by Dr. Mary Allen Staat of Cincinnati Children’s Hospital Medical Center, found that multiple tests significantly increased the likelihood of pathogen detection in children, whether or not they had symptoms. If a single stool sample was tested, the probability of identifying a pathogen was 79%. With two samples, the probability significantly increased to 92%, and for three, it was 100%.

This suggests, Dr. Staat and colleagues wrote, that the current American Academy of Pediatrics’ guidelines should be revised so that three stool specimens, taken 48-72 hours apart, "are submitted and evaluated for all internationally adopted children on arrival to the United States, regardless of gastrointestinal symptoms."

Dr. Elaine Schulte, chair of pediatrics at the Cleveland Clinic and medical director of its international adoption program, said in an interview that the findings had "important" implications for pediatricians and families of internationally adopted children. (The Cleveland Clinic’s international adoption program provides comprehensive medical care to internationally adopted children, including preadoption and postadoption consultation and ongoing care.)

"You can’t rely on kids to be symptomatic," Dr. Schulte said. "For physicians who see internationally adopted kids – but not very many – they may rely on parent assessment, which is not good. Most parents who are adopting internationally have heard about parasites, [but] that doesn’t mean they know what they are, or understand the process of detecting them."

Undiagnosed, untreated parasite infections can lead to malnutrition, and also can be contagious in school and family settings, Dr. Schulte noted. "I’ve taken care of lots of kids who just pass it back and forth among siblings, and it’s really hard to get rid of. Parents also can get infected."

Dr. Staat and her colleagues found the lowest infection rates among children born in South Korea (0%), followed by Guatemala (9%), China (13%), and Vietnam (19%). The highest rates were seen in children from Romania (50%), Bulgaria (54%), Ethiopia (55%), and the Ukraine (74%).

In addition to G. intestinalis, which was present in 19% of children in the study, identified pathogens included Blastocystis hominis (10% of children), Dientamoeba fragilis (5%), and Entamoeba histolytica (1%). Helminths (parasitic worms) were found in 2% of children.

Dr. Staat and her colleagues declared that they had no relevant financial disclosures. Dr. Schulte said that she had no relevant financial disclosures.

A simple, self-reported monthly survey has been shown to help dermatologists identify, monitor, and document adverse effects – including potentially serious psychiatric ones – among young adults being treated with oral isotretinoin.

The 13-question survey was completed monthly, at clinician visits, by 102 patients aged 11-21 years undergoing a course of isotretinoin, according to a study published in the September issue of the Journal of the American Academy of Dermatology (2011;65:517-24 [doi:10.1016/j.jaad.2010.06.040]).

As a group, the study participants completed 760 treatment-months, representing 123 courses of isotretinoin. A total of 729 surveys were returned with complete responses; however, responses from 30 partially completed surveys were counted among the results, reported Ms. Chelsea J. Hodgkiss-Harlow, of the University of California, San Diego, School of Medicine.

The 13-question simple survey included the following symptoms:

• Dry lips

• Dry or bloodshot eyes

• Dry skin

• Muscle aches or pains

• Nosebleeds

• Frequent headaches

• Mood swings

• Depression

• Suicidal thoughts

• Paronychia

• Rash

• Trouble with night vision

• Severe sun sensitivity or sunburn

Mood swings were reported in 7.8% of the 729 surveys, and depression was reported in 1.7%, with no significant difference in incidence seen between patients with a prior mental health diagnosis (n = 12) and those without.

Reports of mood swings or depression were generally transient from survey to survey, "often resolving without a change in isotretinoin dose," the investigators wrote. No reports of suicidal ideation were recorded.

The most frequently reported adverse events mirrored those seen in adults treated with isotretinoin. Dry lips (reported in 94% of surveys) and dry skin (in 72%) were the most common complaints. Younger patients (11-15 years old) and older patients (16-21 years old) had similar adverse event profiles.

The authors noted that the low incidence of psychiatric symptoms among the patients, and the fact that there was no statistical difference in self-reported psychiatric symptoms between patients with a mental health history and those without, suggests extensive psychological screening of isotretinoin-treated adolescents may not be necessary as a first step when monitoring this group.

Instead, they wrote, in-depth screening could be initiated when the simple survey reveals a potential psychiatric problem requiring further evaluation.

Psychiatric screening of adolescents undergoing isotretinoin treatment – particularly those with mental-health histories – has been advised following concerns of possible associations between isotretinoin and depression, psychosis, suicidal ideation, and suicide, they noted.

While the authors conceded that their simplified survey – which asks patients to report experiencing only "mood swings," "depression," or "suicidal thoughts" – lacks the thoroughness of other published depression surveys used in clinical settings to monitor young patients taking isotretinoin, they nonetheless argued that their study’s incidence results were "comparable with those reported in previous studies with more intricate collection methods."

The authors acknowledged that their study’s small size and retrospective design are weaknesses. However, they wrote, the simplified survey could nonetheless be a useful screening tool, "easily implemented in an outpatient clinical setting, and effectively completed by the patient or family at the beginning of their appointment."

The importance of an easily completed survey "should not be underestimated for a screening tool that aims to provide optimal results with monthly patient compliance," they wrote.

The study was funded in part by a grant from the National Institutes of Health. The authors reported no conflicts of interest.

A simple, self-reported monthly survey has been shown to help dermatologists identify, monitor, and document adverse effects – including potentially serious psychiatric ones – among young adults being treated with oral isotretinoin.

The 13-question survey was completed monthly, at clinician visits, by 102 patients aged 11-21 years undergoing a course of isotretinoin, according to a study published in the September issue of the Journal of the American Academy of Dermatology (2011;65:517-24 [doi:10.1016/j.jaad.2010.06.040]).

As a group, the study participants completed 760 treatment-months, representing 123 courses of isotretinoin. A total of 729 surveys were returned with complete responses; however, responses from 30 partially completed surveys were counted among the results, reported Ms. Chelsea J. Hodgkiss-Harlow, of the University of California, San Diego, School of Medicine.

The 13-question simple survey included the following symptoms:

• Dry lips

• Dry or bloodshot eyes

• Dry skin

• Muscle aches or pains

• Nosebleeds

• Frequent headaches

• Mood swings

• Depression

• Suicidal thoughts

• Paronychia

• Rash

• Trouble with night vision

• Severe sun sensitivity or sunburn

Mood swings were reported in 7.8% of the 729 surveys, and depression was reported in 1.7%, with no significant difference in incidence seen between patients with a prior mental health diagnosis (n = 12) and those without.

Reports of mood swings or depression were generally transient from survey to survey, "often resolving without a change in isotretinoin dose," the investigators wrote. No reports of suicidal ideation were recorded.

The most frequently reported adverse events mirrored those seen in adults treated with isotretinoin. Dry lips (reported in 94% of surveys) and dry skin (in 72%) were the most common complaints. Younger patients (11-15 years old) and older patients (16-21 years old) had similar adverse event profiles.

The authors noted that the low incidence of psychiatric symptoms among the patients, and the fact that there was no statistical difference in self-reported psychiatric symptoms between patients with a mental health history and those without, suggests extensive psychological screening of isotretinoin-treated adolescents may not be necessary as a first step when monitoring this group.

Instead, they wrote, in-depth screening could be initiated when the simple survey reveals a potential psychiatric problem requiring further evaluation.

Psychiatric screening of adolescents undergoing isotretinoin treatment – particularly those with mental-health histories – has been advised following concerns of possible associations between isotretinoin and depression, psychosis, suicidal ideation, and suicide, they noted.

While the authors conceded that their simplified survey – which asks patients to report experiencing only "mood swings," "depression," or "suicidal thoughts" – lacks the thoroughness of other published depression surveys used in clinical settings to monitor young patients taking isotretinoin, they nonetheless argued that their study’s incidence results were "comparable with those reported in previous studies with more intricate collection methods."

The authors acknowledged that their study’s small size and retrospective design are weaknesses. However, they wrote, the simplified survey could nonetheless be a useful screening tool, "easily implemented in an outpatient clinical setting, and effectively completed by the patient or family at the beginning of their appointment."

The importance of an easily completed survey "should not be underestimated for a screening tool that aims to provide optimal results with monthly patient compliance," they wrote.

The study was funded in part by a grant from the National Institutes of Health. The authors reported no conflicts of interest.

A simple, self-reported monthly survey has been shown to help dermatologists identify, monitor, and document adverse effects – including potentially serious psychiatric ones – among young adults being treated with oral isotretinoin.

The 13-question survey was completed monthly, at clinician visits, by 102 patients aged 11-21 years undergoing a course of isotretinoin, according to a study published in the September issue of the Journal of the American Academy of Dermatology (2011;65:517-24 [doi:10.1016/j.jaad.2010.06.040]).

As a group, the study participants completed 760 treatment-months, representing 123 courses of isotretinoin. A total of 729 surveys were returned with complete responses; however, responses from 30 partially completed surveys were counted among the results, reported Ms. Chelsea J. Hodgkiss-Harlow, of the University of California, San Diego, School of Medicine.

The 13-question simple survey included the following symptoms:

• Dry lips

• Dry or bloodshot eyes

• Dry skin

• Muscle aches or pains

• Nosebleeds

• Frequent headaches

• Mood swings

• Depression

• Suicidal thoughts

• Paronychia

• Rash

• Trouble with night vision

• Severe sun sensitivity or sunburn

Mood swings were reported in 7.8% of the 729 surveys, and depression was reported in 1.7%, with no significant difference in incidence seen between patients with a prior mental health diagnosis (n = 12) and those without.

Reports of mood swings or depression were generally transient from survey to survey, "often resolving without a change in isotretinoin dose," the investigators wrote. No reports of suicidal ideation were recorded.

The most frequently reported adverse events mirrored those seen in adults treated with isotretinoin. Dry lips (reported in 94% of surveys) and dry skin (in 72%) were the most common complaints. Younger patients (11-15 years old) and older patients (16-21 years old) had similar adverse event profiles.

The authors noted that the low incidence of psychiatric symptoms among the patients, and the fact that there was no statistical difference in self-reported psychiatric symptoms between patients with a mental health history and those without, suggests extensive psychological screening of isotretinoin-treated adolescents may not be necessary as a first step when monitoring this group.

Instead, they wrote, in-depth screening could be initiated when the simple survey reveals a potential psychiatric problem requiring further evaluation.

Psychiatric screening of adolescents undergoing isotretinoin treatment – particularly those with mental-health histories – has been advised following concerns of possible associations between isotretinoin and depression, psychosis, suicidal ideation, and suicide, they noted.

While the authors conceded that their simplified survey – which asks patients to report experiencing only "mood swings," "depression," or "suicidal thoughts" – lacks the thoroughness of other published depression surveys used in clinical settings to monitor young patients taking isotretinoin, they nonetheless argued that their study’s incidence results were "comparable with those reported in previous studies with more intricate collection methods."

The authors acknowledged that their study’s small size and retrospective design are weaknesses. However, they wrote, the simplified survey could nonetheless be a useful screening tool, "easily implemented in an outpatient clinical setting, and effectively completed by the patient or family at the beginning of their appointment."

The importance of an easily completed survey "should not be underestimated for a screening tool that aims to provide optimal results with monthly patient compliance," they wrote.

The study was funded in part by a grant from the National Institutes of Health. The authors reported no conflicts of interest.

Somatropin, or recombinant human growth hormone, may not be associated with an increased risk of death, the Food and Drug Administration said Aug. 5.

The agency is continuing a safety review initiated in late 2010 following results from the ongoing, publicly funded, French-led Santé Adulte GH Enfant (SAGhE) cohort study designed to enroll 30,000 Europeans treated with somatropin as children.

The study is intended to shed light on the long-term health effects of childhood treatment with somatropin, including long-term mortality and cancer incidence.

The FDA has determined that the mortality evidence from the study is as yet inconclusive.

The agency explained in an update Aug. 4 that it had identified a number of weaknesses in the study "that limit the interpretability of the study results."

Additional literature reviews did not add to evidence of a link between recombinant human growth hormone and an increased risk of death, the FDA said.  

"Healthcare professionals and patients should continue to prescribe and use recombinant human growth hormone according to the labeled recommendations," the agency said, adding that it would continue to review the issue following the receipt next spring of additional data from the French study.

The FDA said that it would update the public on somatropin "when new information is available."

Somatropin, or recombinant human growth hormone, may not be associated with an increased risk of death, the Food and Drug Administration said Aug. 5.

The agency is continuing a safety review initiated in late 2010 following results from the ongoing, publicly funded, French-led Santé Adulte GH Enfant (SAGhE) cohort study designed to enroll 30,000 Europeans treated with somatropin as children.

The study is intended to shed light on the long-term health effects of childhood treatment with somatropin, including long-term mortality and cancer incidence.

The FDA has determined that the mortality evidence from the study is as yet inconclusive.

The agency explained in an update Aug. 4 that it had identified a number of weaknesses in the study "that limit the interpretability of the study results."

Additional literature reviews did not add to evidence of a link between recombinant human growth hormone and an increased risk of death, the FDA said.  

"Healthcare professionals and patients should continue to prescribe and use recombinant human growth hormone according to the labeled recommendations," the agency said, adding that it would continue to review the issue following the receipt next spring of additional data from the French study.

The FDA said that it would update the public on somatropin "when new information is available."

Somatropin, or recombinant human growth hormone, may not be associated with an increased risk of death, the Food and Drug Administration said Aug. 5.

The agency is continuing a safety review initiated in late 2010 following results from the ongoing, publicly funded, French-led Santé Adulte GH Enfant (SAGhE) cohort study designed to enroll 30,000 Europeans treated with somatropin as children.

The study is intended to shed light on the long-term health effects of childhood treatment with somatropin, including long-term mortality and cancer incidence.

The FDA has determined that the mortality evidence from the study is as yet inconclusive.

The agency explained in an update Aug. 4 that it had identified a number of weaknesses in the study "that limit the interpretability of the study results."

Additional literature reviews did not add to evidence of a link between recombinant human growth hormone and an increased risk of death, the FDA said.  

"Healthcare professionals and patients should continue to prescribe and use recombinant human growth hormone according to the labeled recommendations," the agency said, adding that it would continue to review the issue following the receipt next spring of additional data from the French study.

The FDA said that it would update the public on somatropin "when new information is available."

The Food and Drug Administration said August 5 that it had approved new labels for the diabetes drug pioglitazone to include warnings about bladder cancer risk.

The announcement follows the agency’s June 15 statement explaining its intention to craft new warnings on pioglitazone in light of interim findings from a 10-year epidemiologic study (Diabetes Care 2011;34:916-22) that saw an increased risk of bladder cancer among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of the drug.

The study showed no significant increase in the risk for bladder cancer in patients ever exposed to pioglitazone, compared with those never exposed to pioglitazone (hazard ratio, 1.2). By contrast, a year or more of pioglitazone therapy was associated with a 40% increase in risk (HR, 1.4).

The new warnings recommend that pioglitazone, marketed in the United States as Actos (or in combination with metformin as Actoplus Met, and with glimepiride as Duetact) not be given to patients with active bladder cancer and that the drug be used with caution in those with prior bladder cancer.

The updated labels recommend that patients contact a health care professional if they experience "any sign of blood in the urine or a red color in the urine or other symptoms such as new or worsening urinary urgency or pain on urination since starting pioglitazone, as these may be due to bladder cancer."

An ongoing study in France resulted in the suspension of pioglitazone there in June and prompted a broader review by the European Medicines Agency.

On July 21, the European Medicines Agency announced its intention to alter warnings on pioglitazone to reflect the known bladder cancer risk; however, the agency stopped short of recommending that its marketing be suspended in the European Union, concluding in that the risk-benefit profile of pioglitazone continued to be favorable if risks were "reduced by appropriate patient selection and exclusion."

The Food and Drug Administration said August 5 that it had approved new labels for the diabetes drug pioglitazone to include warnings about bladder cancer risk.

The announcement follows the agency’s June 15 statement explaining its intention to craft new warnings on pioglitazone in light of interim findings from a 10-year epidemiologic study (Diabetes Care 2011;34:916-22) that saw an increased risk of bladder cancer among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of the drug.

The study showed no significant increase in the risk for bladder cancer in patients ever exposed to pioglitazone, compared with those never exposed to pioglitazone (hazard ratio, 1.2). By contrast, a year or more of pioglitazone therapy was associated with a 40% increase in risk (HR, 1.4).

The new warnings recommend that pioglitazone, marketed in the United States as Actos (or in combination with metformin as Actoplus Met, and with glimepiride as Duetact) not be given to patients with active bladder cancer and that the drug be used with caution in those with prior bladder cancer.

The updated labels recommend that patients contact a health care professional if they experience "any sign of blood in the urine or a red color in the urine or other symptoms such as new or worsening urinary urgency or pain on urination since starting pioglitazone, as these may be due to bladder cancer."

An ongoing study in France resulted in the suspension of pioglitazone there in June and prompted a broader review by the European Medicines Agency.

On July 21, the European Medicines Agency announced its intention to alter warnings on pioglitazone to reflect the known bladder cancer risk; however, the agency stopped short of recommending that its marketing be suspended in the European Union, concluding in that the risk-benefit profile of pioglitazone continued to be favorable if risks were "reduced by appropriate patient selection and exclusion."

The Food and Drug Administration said August 5 that it had approved new labels for the diabetes drug pioglitazone to include warnings about bladder cancer risk.

The announcement follows the agency’s June 15 statement explaining its intention to craft new warnings on pioglitazone in light of interim findings from a 10-year epidemiologic study (Diabetes Care 2011;34:916-22) that saw an increased risk of bladder cancer among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of the drug.

The study showed no significant increase in the risk for bladder cancer in patients ever exposed to pioglitazone, compared with those never exposed to pioglitazone (hazard ratio, 1.2). By contrast, a year or more of pioglitazone therapy was associated with a 40% increase in risk (HR, 1.4).

The new warnings recommend that pioglitazone, marketed in the United States as Actos (or in combination with metformin as Actoplus Met, and with glimepiride as Duetact) not be given to patients with active bladder cancer and that the drug be used with caution in those with prior bladder cancer.

The updated labels recommend that patients contact a health care professional if they experience "any sign of blood in the urine or a red color in the urine or other symptoms such as new or worsening urinary urgency or pain on urination since starting pioglitazone, as these may be due to bladder cancer."

An ongoing study in France resulted in the suspension of pioglitazone there in June and prompted a broader review by the European Medicines Agency.

On July 21, the European Medicines Agency announced its intention to alter warnings on pioglitazone to reflect the known bladder cancer risk; however, the agency stopped short of recommending that its marketing be suspended in the European Union, concluding in that the risk-benefit profile of pioglitazone continued to be favorable if risks were "reduced by appropriate patient selection and exclusion."

A large U.K. cohort study has shown that tricyclics may be safer for treating depression in people older than 65 years than are the more commonly prescribed selective serotonin reuptake inhibitors.

The findings, published online Aug. 2 in BMJ (doi:10.1136/bmj.d4551), are striking, considering how frequently SSRIs are prescribed to people aged 65 and older. Current guidelines published by the U.K.’s National Institute for Health and Clinical Excellence promote SSRIs as a first choice among drug treatments for adults with depression, including older adults.

The results are surprising "mainly because it isn’t what we expected from the guidance. There’s a general feeling that the SSRIs are safer," the study’s lead investigator, Carol Coupland, Ph.D., of the University of Nottingham (England), said in an interview.

Compared directly with tricyclic antidepressants, SSRIs were associated with significantly higher rates of all-cause death (adjusted hazard ratio, 1.32), stroke or transient ischemic attack (HR, 1.15), fractures (HR, 1.26), falls (HR, 1.27), hyponatremia (HR, 1.44), and epilepsy or seizures (HR, 1.80). There was no significant difference seen for attempted suicide or self-harm (HR, 1.27).

Absolute risks for all-cause mortality over 1 year were 7.04% for patients not taking antidepressants, 8.12% for those taking TCAs, 10.61% for SSRIs, and 11.43% for other antidepressants.

In this study the TCAs tended to be prescribed at smaller doses than the SSRIs. Of the group taking TCAs, 70% were taking less than half the defined daily dose, compared with 13.8% of those on SSRIs. The researchers noted significant trends (P less than .01) corresponding with dosages of TCAs and SSRIs for all-cause mortality, falls, and epilepsy or seizures.

All 60,746 subjects in Dr. Coupland and colleagues’ linked cohort study were aged 65-100 years (mean age, 75 years; 67% were women) and had been diagnosed with depression by their primary care practitioners in 1996-2008. Of these, 89% were prescribed at least one antidepressant drug, which 55% of the time was an SSRI. About a third of the subjects who had been prescribed a drug received a tricyclic antidepressant. The rest (13.5%) received drugs in other classes; only 0.2% of patients in the study were prescribed MAO inhibitors – too small a group to enter into the analysis.

In all, 11 antidepressant drugs (5 SSRIs, 4 TCAs, and 2 in other categories) accounted for 96% of prescriptions in the cohort, and median duration of treatment was 1 year. The researchers evaluated a host of adverse outcomes both for the drug class and for individual drugs.

The cohort presented with a variety of comorbidities typical for the age bracket, and investigators adjusted results for the potential confounding effects of these diseases and the drugs used to treat them, along with smoking status, socioeconomic status, and other potential confounding factors.

The results, Dr. Coupland said, "suggest possibly an area for concern. We don’t want to be alarmist. It’s very new research and needs to be confirmed by other studies," particularly randomized controlled trials.

The investigators did note significant differences in adverse outcome risks even among drugs in the same class. One drug in the tricyclic group, trazodone, was associated with the highest absolute risk for all-cause death in the cohort (12.44% in 1 year) and one of the highest for attempted suicide or self-harm (1.2% in 1 year).

Three SSRIs – citalopram, escitalopram, and fluoxetine – were shown associated with increased risk of hyponatremia, while two other SSRIs, paroxetine and sertraline, were not.

The two non-SSRI, non-TCA drugs – mirtazapine and venlafaxine – were shown associated with increased risk of suicide or self-harm along with all-cause death and stroke or transient ischemic attack, with venlafaxine additionally associated with higher risk of fracture and epilepsy or seizures.

Dr. Coupland and colleagues noted several limitations for their study, mainly its observational design and the accompanying susceptibility to confounding by indication, channeling bias, and residual confounding.

However, in an editorial (10.1136/bmj.d4660) accompanying their study, Dr. Ian B. Hickie of the Brain and Mind Research Institute at the University of Sydney, said the findings have "clear implications for more informed prescribing and enhanced clinical monitoring" regardless of the study design.

Given the potential harms outlined in the study, Dr. Hickie wrote, "the decision to prescribe for an older person with depression should not be taken lightly."

The study was funded by the U.K.’s National Institute for Health Research. Dr. Coupland and colleagues declared no conflicts of interest. Coauthors Richard Morriss of the University of Nottingham disclosed receiving past financial support for speaking at meetings sponsored by pharmaceutical companies. Editorialist Dr. Hickie disclosed no conflicts of interest related to his editorial, but acknowledged participation at industry-sponsored depression awareness seminars.

A large U.K. cohort study has shown that tricyclics may be safer for treating depression in people older than 65 years than are the more commonly prescribed selective serotonin reuptake inhibitors.

The findings, published online Aug. 2 in BMJ (doi:10.1136/bmj.d4551), are striking, considering how frequently SSRIs are prescribed to people aged 65 and older. Current guidelines published by the U.K.’s National Institute for Health and Clinical Excellence promote SSRIs as a first choice among drug treatments for adults with depression, including older adults.

The results are surprising "mainly because it isn’t what we expected from the guidance. There’s a general feeling that the SSRIs are safer," the study’s lead investigator, Carol Coupland, Ph.D., of the University of Nottingham (England), said in an interview.

Compared directly with tricyclic antidepressants, SSRIs were associated with significantly higher rates of all-cause death (adjusted hazard ratio, 1.32), stroke or transient ischemic attack (HR, 1.15), fractures (HR, 1.26), falls (HR, 1.27), hyponatremia (HR, 1.44), and epilepsy or seizures (HR, 1.80). There was no significant difference seen for attempted suicide or self-harm (HR, 1.27).

Absolute risks for all-cause mortality over 1 year were 7.04% for patients not taking antidepressants, 8.12% for those taking TCAs, 10.61% for SSRIs, and 11.43% for other antidepressants.

In this study the TCAs tended to be prescribed at smaller doses than the SSRIs. Of the group taking TCAs, 70% were taking less than half the defined daily dose, compared with 13.8% of those on SSRIs. The researchers noted significant trends (P less than .01) corresponding with dosages of TCAs and SSRIs for all-cause mortality, falls, and epilepsy or seizures.

All 60,746 subjects in Dr. Coupland and colleagues’ linked cohort study were aged 65-100 years (mean age, 75 years; 67% were women) and had been diagnosed with depression by their primary care practitioners in 1996-2008. Of these, 89% were prescribed at least one antidepressant drug, which 55% of the time was an SSRI. About a third of the subjects who had been prescribed a drug received a tricyclic antidepressant. The rest (13.5%) received drugs in other classes; only 0.2% of patients in the study were prescribed MAO inhibitors – too small a group to enter into the analysis.

In all, 11 antidepressant drugs (5 SSRIs, 4 TCAs, and 2 in other categories) accounted for 96% of prescriptions in the cohort, and median duration of treatment was 1 year. The researchers evaluated a host of adverse outcomes both for the drug class and for individual drugs.

The cohort presented with a variety of comorbidities typical for the age bracket, and investigators adjusted results for the potential confounding effects of these diseases and the drugs used to treat them, along with smoking status, socioeconomic status, and other potential confounding factors.

The results, Dr. Coupland said, "suggest possibly an area for concern. We don’t want to be alarmist. It’s very new research and needs to be confirmed by other studies," particularly randomized controlled trials.

The investigators did note significant differences in adverse outcome risks even among drugs in the same class. One drug in the tricyclic group, trazodone, was associated with the highest absolute risk for all-cause death in the cohort (12.44% in 1 year) and one of the highest for attempted suicide or self-harm (1.2% in 1 year).

Three SSRIs – citalopram, escitalopram, and fluoxetine – were shown associated with increased risk of hyponatremia, while two other SSRIs, paroxetine and sertraline, were not.

The two non-SSRI, non-TCA drugs – mirtazapine and venlafaxine – were shown associated with increased risk of suicide or self-harm along with all-cause death and stroke or transient ischemic attack, with venlafaxine additionally associated with higher risk of fracture and epilepsy or seizures.

Dr. Coupland and colleagues noted several limitations for their study, mainly its observational design and the accompanying susceptibility to confounding by indication, channeling bias, and residual confounding.

However, in an editorial (10.1136/bmj.d4660) accompanying their study, Dr. Ian B. Hickie of the Brain and Mind Research Institute at the University of Sydney, said the findings have "clear implications for more informed prescribing and enhanced clinical monitoring" regardless of the study design.

Given the potential harms outlined in the study, Dr. Hickie wrote, "the decision to prescribe for an older person with depression should not be taken lightly."

The study was funded by the U.K.’s National Institute for Health Research. Dr. Coupland and colleagues declared no conflicts of interest. Coauthors Richard Morriss of the University of Nottingham disclosed receiving past financial support for speaking at meetings sponsored by pharmaceutical companies. Editorialist Dr. Hickie disclosed no conflicts of interest related to his editorial, but acknowledged participation at industry-sponsored depression awareness seminars.

A large U.K. cohort study has shown that tricyclics may be safer for treating depression in people older than 65 years than are the more commonly prescribed selective serotonin reuptake inhibitors.

The findings, published online Aug. 2 in BMJ (doi:10.1136/bmj.d4551), are striking, considering how frequently SSRIs are prescribed to people aged 65 and older. Current guidelines published by the U.K.’s National Institute for Health and Clinical Excellence promote SSRIs as a first choice among drug treatments for adults with depression, including older adults.

The results are surprising "mainly because it isn’t what we expected from the guidance. There’s a general feeling that the SSRIs are safer," the study’s lead investigator, Carol Coupland, Ph.D., of the University of Nottingham (England), said in an interview.

Compared directly with tricyclic antidepressants, SSRIs were associated with significantly higher rates of all-cause death (adjusted hazard ratio, 1.32), stroke or transient ischemic attack (HR, 1.15), fractures (HR, 1.26), falls (HR, 1.27), hyponatremia (HR, 1.44), and epilepsy or seizures (HR, 1.80). There was no significant difference seen for attempted suicide or self-harm (HR, 1.27).

Absolute risks for all-cause mortality over 1 year were 7.04% for patients not taking antidepressants, 8.12% for those taking TCAs, 10.61% for SSRIs, and 11.43% for other antidepressants.

In this study the TCAs tended to be prescribed at smaller doses than the SSRIs. Of the group taking TCAs, 70% were taking less than half the defined daily dose, compared with 13.8% of those on SSRIs. The researchers noted significant trends (P less than .01) corresponding with dosages of TCAs and SSRIs for all-cause mortality, falls, and epilepsy or seizures.

All 60,746 subjects in Dr. Coupland and colleagues’ linked cohort study were aged 65-100 years (mean age, 75 years; 67% were women) and had been diagnosed with depression by their primary care practitioners in 1996-2008. Of these, 89% were prescribed at least one antidepressant drug, which 55% of the time was an SSRI. About a third of the subjects who had been prescribed a drug received a tricyclic antidepressant. The rest (13.5%) received drugs in other classes; only 0.2% of patients in the study were prescribed MAO inhibitors – too small a group to enter into the analysis.

In all, 11 antidepressant drugs (5 SSRIs, 4 TCAs, and 2 in other categories) accounted for 96% of prescriptions in the cohort, and median duration of treatment was 1 year. The researchers evaluated a host of adverse outcomes both for the drug class and for individual drugs.

The cohort presented with a variety of comorbidities typical for the age bracket, and investigators adjusted results for the potential confounding effects of these diseases and the drugs used to treat them, along with smoking status, socioeconomic status, and other potential confounding factors.

The results, Dr. Coupland said, "suggest possibly an area for concern. We don’t want to be alarmist. It’s very new research and needs to be confirmed by other studies," particularly randomized controlled trials.

The investigators did note significant differences in adverse outcome risks even among drugs in the same class. One drug in the tricyclic group, trazodone, was associated with the highest absolute risk for all-cause death in the cohort (12.44% in 1 year) and one of the highest for attempted suicide or self-harm (1.2% in 1 year).

Three SSRIs – citalopram, escitalopram, and fluoxetine – were shown associated with increased risk of hyponatremia, while two other SSRIs, paroxetine and sertraline, were not.

The two non-SSRI, non-TCA drugs – mirtazapine and venlafaxine – were shown associated with increased risk of suicide or self-harm along with all-cause death and stroke or transient ischemic attack, with venlafaxine additionally associated with higher risk of fracture and epilepsy or seizures.

Dr. Coupland and colleagues noted several limitations for their study, mainly its observational design and the accompanying susceptibility to confounding by indication, channeling bias, and residual confounding.

However, in an editorial (10.1136/bmj.d4660) accompanying their study, Dr. Ian B. Hickie of the Brain and Mind Research Institute at the University of Sydney, said the findings have "clear implications for more informed prescribing and enhanced clinical monitoring" regardless of the study design.

Given the potential harms outlined in the study, Dr. Hickie wrote, "the decision to prescribe for an older person with depression should not be taken lightly."

The study was funded by the U.K.’s National Institute for Health Research. Dr. Coupland and colleagues declared no conflicts of interest. Coauthors Richard Morriss of the University of Nottingham disclosed receiving past financial support for speaking at meetings sponsored by pharmaceutical companies. Editorialist Dr. Hickie disclosed no conflicts of interest related to his editorial, but acknowledged participation at industry-sponsored depression awareness seminars.

Major Finding: Neither antiretroviral therapy with tenofovir nor ART with boosted protease inhibitors was significantly associated with an increased risk of osteoporotic fracture in HIV-infected patients after a median 4.5 years of follow-up and adjustment for possibly confounding variables.

Data Source: A retrospective cohort study of 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Disclosures: The investigators did not report whether they had any relevant financial disclosures.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the meeting focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group's retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens during 1988-2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to linked with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant after adjustment for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral BMD (OR, 2.24) but not low lumbar BMD.

Dr. Guaraldi said that further studies were needed to determine “how heart and bone disease talk to each other” in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone density and cardiovascular risks in this patient group.

Major Finding: Neither antiretroviral therapy with tenofovir nor ART with boosted protease inhibitors was significantly associated with an increased risk of osteoporotic fracture in HIV-infected patients after a median 4.5 years of follow-up and adjustment for possibly confounding variables.

Data Source: A retrospective cohort study of 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Disclosures: The investigators did not report whether they had any relevant financial disclosures.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the meeting focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group's retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens during 1988-2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to linked with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant after adjustment for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral BMD (OR, 2.24) but not low lumbar BMD.

Dr. Guaraldi said that further studies were needed to determine “how heart and bone disease talk to each other” in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone density and cardiovascular risks in this patient group.

Major Finding: Neither antiretroviral therapy with tenofovir nor ART with boosted protease inhibitors was significantly associated with an increased risk of osteoporotic fracture in HIV-infected patients after a median 4.5 years of follow-up and adjustment for possibly confounding variables.

Data Source: A retrospective cohort study of 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Disclosures: The investigators did not report whether they had any relevant financial disclosures.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the meeting focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group's retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens during 1988-2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to linked with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant after adjustment for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral BMD (OR, 2.24) but not low lumbar BMD.

Dr. Guaraldi said that further studies were needed to determine “how heart and bone disease talk to each other” in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone density and cardiovascular risks in this patient group.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of a school-based vaccination program, according to a study by Australian researchers.

The population-based study, published online in the Lancet, examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085–92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research.

Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger.

In older age groups, there were no declines.

Vaccination records were not linked to screening data in the study by Dr. Brotherton and her colleaguesí However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; however, some younger girls are screened at the discretion of their health care providers.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, “reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls.”

The researchers also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women who were older than 18 years of age.

Only women who were younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the Centers for Disease Control and Prevention, urged caution in interpreting the findings.

They said that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will require much more data and several decades to establish.

“The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect,” Dr. Saraiya and Dr. Hariri wrote. “However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria.”

The findings may have been affected by health care providers' screening and managing vaccinated patients less aggressively, “especially girls younger than the recommended screening age of 18 years,” Dr. Saraiya and Dr. Hariri argued.

Additionally, “with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18–20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high,” Dr. Saraiya and Dr. Hariri wrote.

However, the study found no decrease in this oldest age group.

Dr. Brotherton and her coinvestigators acknowledged that the population-based study design was a weakness, and they noted that further studies linking vaccination and cytology data would be needed to confirm the findings of their study.

However, they wrote, “we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease.”

Human papillomavirus types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of a school-based vaccination program, according to a study by Australian researchers.

The population-based study, published online in the Lancet, examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085–92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research.

Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger.

In older age groups, there were no declines.

Vaccination records were not linked to screening data in the study by Dr. Brotherton and her colleaguesí However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; however, some younger girls are screened at the discretion of their health care providers.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, “reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls.”

The researchers also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women who were older than 18 years of age.

Only women who were younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the Centers for Disease Control and Prevention, urged caution in interpreting the findings.

They said that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will require much more data and several decades to establish.

“The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect,” Dr. Saraiya and Dr. Hariri wrote. “However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria.”

The findings may have been affected by health care providers' screening and managing vaccinated patients less aggressively, “especially girls younger than the recommended screening age of 18 years,” Dr. Saraiya and Dr. Hariri argued.

Additionally, “with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18–20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high,” Dr. Saraiya and Dr. Hariri wrote.

However, the study found no decrease in this oldest age group.

Dr. Brotherton and her coinvestigators acknowledged that the population-based study design was a weakness, and they noted that further studies linking vaccination and cytology data would be needed to confirm the findings of their study.

However, they wrote, “we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease.”

Human papillomavirus types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of a school-based vaccination program, according to a study by Australian researchers.

The population-based study, published online in the Lancet, examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085–92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research.

Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger.

In older age groups, there were no declines.

Vaccination records were not linked to screening data in the study by Dr. Brotherton and her colleaguesí However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; however, some younger girls are screened at the discretion of their health care providers.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, “reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls.”

The researchers also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women who were older than 18 years of age.

Only women who were younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the Centers for Disease Control and Prevention, urged caution in interpreting the findings.

They said that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will require much more data and several decades to establish.

“The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect,” Dr. Saraiya and Dr. Hariri wrote. “However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria.”

The findings may have been affected by health care providers' screening and managing vaccinated patients less aggressively, “especially girls younger than the recommended screening age of 18 years,” Dr. Saraiya and Dr. Hariri argued.

Additionally, “with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18–20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high,” Dr. Saraiya and Dr. Hariri wrote.

However, the study found no decrease in this oldest age group.

Dr. Brotherton and her coinvestigators acknowledged that the population-based study design was a weakness, and they noted that further studies linking vaccination and cytology data would be needed to confirm the findings of their study.

However, they wrote, “we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease.”

Human papillomavirus types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.