Kate Johnson

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the meeting, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV virus, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck's Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk family practice setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24%, respectively, at 2 years (Cancer Epidemiol. Biomarkers Prev. 2003;12:485-90).

“We couldn't be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There's no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer…. I've got several of them in their 20s and early 30s and it ruins their lives, and they can't have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines], I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn't guarantee 100% protection. It's an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won't take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative”—it's “terrible and painful,” she added.

Last year a prominent editorial and article in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck's Gardasil “was named the pharmaceutical 'brand of the year' for building a 'market out of thin air.'”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It's not a slam dunk that if you get the HPV vaccine you'll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won't know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim, and Bayer. Dr. Plante reported having no conflicts of interest.

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the meeting, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV virus, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck's Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk family practice setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24%, respectively, at 2 years (Cancer Epidemiol. Biomarkers Prev. 2003;12:485-90).

“We couldn't be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There's no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer…. I've got several of them in their 20s and early 30s and it ruins their lives, and they can't have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines], I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn't guarantee 100% protection. It's an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won't take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative”—it's “terrible and painful,” she added.

Last year a prominent editorial and article in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck's Gardasil “was named the pharmaceutical 'brand of the year' for building a 'market out of thin air.'”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It's not a slam dunk that if you get the HPV vaccine you'll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won't know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim, and Bayer. Dr. Plante reported having no conflicts of interest.

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the meeting, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV virus, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck's Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk family practice setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24%, respectively, at 2 years (Cancer Epidemiol. Biomarkers Prev. 2003;12:485-90).

“We couldn't be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There's no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer…. I've got several of them in their 20s and early 30s and it ruins their lives, and they can't have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines], I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn't guarantee 100% protection. It's an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won't take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative”—it's “terrible and painful,” she added.

Last year a prominent editorial and article in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck's Gardasil “was named the pharmaceutical 'brand of the year' for building a 'market out of thin air.'”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It's not a slam dunk that if you get the HPV vaccine you'll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won't know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim, and Bayer. Dr. Plante reported having no conflicts of interest.

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the annual meeting of the Society of Obstetricians and Gynaecologists of Canada, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck’s Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV and in which infection is very common,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24% respectively at 2 years (Cancer Epidemiol Biomarkers Prev. 2003;12:485-90).

“We couldn’t be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There’s no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer ... I’ve got several of them in their 20s and early 30s and it ruins their lives, and they can’t have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines] I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn’t guarantee 100% protection. It’s an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won’t take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative” – it’s “terrible and painful,” she added.

Last year a prominent article and editorial in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck’s Gardasil “was named the pharmaceutical ‘brand of the year’ for building a ‘market out of thin air.’ ”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It’s not a slam dunk that if you get the HPV vaccine you’ll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won’t know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

As of Jan. 31, 2010, there were 49 U.S. reports of death among females who had received Gardasil, according to the Centers for Disease Control and Prevention. Twenty eight of these reports have been confirmed and 21 remain unconfirmed. In the 28 confirmed reports, “there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine,” according to a CDC statement.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim and Bayer. Dr. Plante reported having no conflicts of interest.

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the annual meeting of the Society of Obstetricians and Gynaecologists of Canada, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck’s Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV and in which infection is very common,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24% respectively at 2 years (Cancer Epidemiol Biomarkers Prev. 2003;12:485-90).

“We couldn’t be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There’s no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer ... I’ve got several of them in their 20s and early 30s and it ruins their lives, and they can’t have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines] I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn’t guarantee 100% protection. It’s an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won’t take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative” – it’s “terrible and painful,” she added.

Last year a prominent article and editorial in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck’s Gardasil “was named the pharmaceutical ‘brand of the year’ for building a ‘market out of thin air.’ ”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It’s not a slam dunk that if you get the HPV vaccine you’ll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won’t know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

As of Jan. 31, 2010, there were 49 U.S. reports of death among females who had received Gardasil, according to the Centers for Disease Control and Prevention. Twenty eight of these reports have been confirmed and 21 remain unconfirmed. In the 28 confirmed reports, “there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine,” according to a CDC statement.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim and Bayer. Dr. Plante reported having no conflicts of interest.

MONTREAL — Uptake of the human papillomavirus vaccination is too slow, say some experts, while others still question whether enough is known about the risk-benefit ratio to deem the vaccination truly necessary.

In an industry-sponsored symposium held during the annual meeting of the Society of Obstetricians and Gynaecologists of Canada, Dr. William Fisher, a consultant to Merck, strongly urged physicians to make HPV vaccination a routine part of their practice.

There are about 100 strains of HPV, with 15 considered oncogenic. HPV strains 16 and 18 are responsible for about 70% of cervical cancer, while strains 6 and 11 are responsible for genital warts. Merck’s Gardasil vaccine targets all four strains, while Cervarix (GlaxoSmithKline PLC) targets the oncogenic strains 16 and 18.

“HPV vaccine would seem to be a very reasonable form of protection, for both men and women, who may be sexually active in an environment characterized by a very high level of HPV and in which infection is very common,” as the infection may have serious health consequences for the individual and his or her partner, said Dr. Fisher, a professor in the departments of psychology and obstetrics and gynecology at the University of Western Ontario, London.

To illustrate the prevalence of HPV infection, Dr. Fisher noted a 25% rate of infection with high-risk oncogenic strains of HPV among Canadian teenage girls, aged 15-19 years, in a low-risk setting who were negative for HPV the previous year (CMAJ 2003;168:421-5).

Similarly, among a group of 621 university-age women tested every 6 months for 2 years, the rate of newly acquired high- and low-risk HPV strains was 13% at 1 year, and 29% and 24% respectively at 2 years (Cancer Epidemiol Biomarkers Prev. 2003;12:485-90).

“We couldn’t be talking more clearly about a sociosexual epidemic,” he said. “This is a social disease on steroids,” said Dr. Fisher, who is also a research affiliate at the Center for Health, Intervention, and Prevention at the University of Connecticut, in Storrs.

In a recent study involving young Canadian couples, HPV was present in 64% of new couples and the oncogenic HPV-16 strain was the most common strain found at baseline.

Concordance of strains was 41% at baseline and grew to 68% at 6 months, he said (Epidemiology 2010;21:31-7). “There’s no doubt in new relationships that HPV is rapidly becoming part of the sociocultural landscape,” Dr. Fisher said.

While there is a well-established link between high-risk HPV and gynecologic cancers, HPV-related head and neck cancers are “probably the newest sexually transmitted infections on the radar,” he said.

A recent study shows that in Sweden the prevalence of oncogenic HPV strains in head and neck cancer biopsies has increased from 23% in the 1970s to 77% by 2005 (Int. J. Cancer 2009;125:362-6).

In addition, a study from this year shows that the risk of HPV-related head and neck cancer, while increased with six or more coital partners (odds ratio 1.25), more than triples with more than four oral-genital partners (OR 3.36). “Oral-genital sex is the new handshake, and it is actually likely that people have more oral-genital partners than coital partners,” Dr. Fisher added.

Yet while Canadian and U.S. authorities recommend HPV vaccination in young girls and women, and school-based vaccination programs are offered across Canada, such recommendations have not resulted in mass vaccination, he said. A recent study suggests that only about one-third of American girls, aged 13-17 years, have been vaccinated (Am. J. Prev. Med. 2010;38:525-33).

Dr. Marie Plante, president of the Society of Gynecologic Oncologists of Canada, said that as a gynecologic oncologist she sees the downside of such low vaccination rates. “We treat women with cervical cancer ... I’ve got several of them in their 20s and early 30s and it ruins their lives, and they can’t have children sometimes. So we see the frustrating part because it could have been prevented,” said Dr. Plante, associate professor of obstetrics and gynecology, and chief of the gynecologic oncology division at Laval University in Quebec City. She estimates that about 50% of cervical cancer cases she sees are in women whose regular screening had failed to identify it.

“As much as I am very critical of the push from the companies [to market their vaccines] I will tell you that honestly I think the vaccine is safe,” Dr. Plante continued. Is it necessary? “No, it is not necessary,” she said. “It doesn’t guarantee 100% protection. It’s an option you have to reduce the chances that you develop precancerous cells. In most cases this will be treated quickly and won’t take your life away.” Importantly, the vaccine also reduces the potentially significant burden of genital warts, the experience of which is “amazingly negative” – it’s “terrible and painful,” she added.

Last year a prominent article and editorial in the JAMA questioned the medical arguments for vaccination, as well as the ethics of aggressive marketing campaigns from pharmaceutical companies (JAMA 2009;302:795-6, and 781-6).

“If the potential benefits are substantial, most individuals would be willing to accept the risks. But the net benefit of the HPV vaccine to women is uncertain. Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened,” wrote Dr. Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association.

In their article, Sheila Rothman, Ph.D., and David Rothman, Ph.D., of Columbia University, New York, noted that in 2006, Merck’s Gardasil “was named the pharmaceutical ‘brand of the year’ for building a ‘market out of thin air.’ ”

Alan Cassels, a drug policy researcher at the University of Victoria (B.C.), was critical. “It’s not a slam dunk that if you get the HPV vaccine you’ll be prevented from developing cancer,” he said in an interview. He compared the vaccine to cholesterol-lowering drugs. “Yes, we can prove that a drug lowers cholesterol, but the question is whether it prevents heart attacks and strokes. So, while the HPV vaccine may prevent transmission of the virus, will that really result in [fewer] cancers? We won’t know for 10 or 20 years down the road.”

Given the uncertainty of benefit, or the duration of efficacy, Mr. Cassels cautioned that the risks of any intervention should be minimal, which is not the case with the HPV vaccine, he said.

As of Jan. 31, 2010, there were 49 U.S. reports of death among females who had received Gardasil, according to the Centers for Disease Control and Prevention. Twenty eight of these reports have been confirmed and 21 remain unconfirmed. In the 28 confirmed reports, “there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine,” according to a CDC statement.

Merck sponsored the symposium Dr. Fisher disclosed that he has been a consultant for Merck, Boehringer Ingelheim and Bayer. Dr. Plante reported having no conflicts of interest.

Major Finding: The rates of preeclampsia were not significantly different between groups, occurring in 7.2% of the women receiving vitamin C and vitamin E and 6.7% of the placebo group.

Data Source: A large multicenter trial of 10,154 low-risk, nulliparous women from 16 clinical centers.

Disclosures: The study was supported by grants from the National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Some of the investigators disclosed financial conflicts.

Daily supplementation with vitamins C and E starting between 9 and 16 weeks' gestation did not reduce the rate of pregnancy-associated hypertension, according to a large multicenter trial in low-risk, nulliparous women.

The findings “provide no support for the use of vitamin C and E supplementation in pregnancy to reduce the risk of preeclampsia or its complications,” wrote Dr. James M. Roberts of the University of Pittsburgh and his colleagues (N. Engl. J. Med. 2010;362:1282-91).

The study randomized 10,154 nulliparous women from 16 clinical centers. All women had singleton pregnancies, with gestational age at randomization ranging between 9 weeks, 0 days and 16 weeks, 6 days. The women were randomly assigned to take 1,000 mg of vitamin C and 400 IU of vitamin E daily, or matching placebo, until the end of their pregnancies. They returned any unused study drug each month and received a new batch, at which time they reported any side effects, and had their blood pressure and urine protein levels measured.

The primary outcome of the study was a composite of pregnancy-associated hypertension and serious adverse outcomes in the mother, fetus, or neonate, while the secondary outcomes included preeclampsia and other maternal and neonatal outcomes.

After some subjects were lost to follow-up or removed, a total of 4,993 women from the vitamin arm and 4,976 from the placebo arm were included in the final analysis.

Neither the primary or secondary outcomes of the study were significantly affected by vitamin treatment. A total of 6.1% of the vitamin group and 5.7% of the placebo group met criteria for the primary outcome. Similarly, the rates of the secondary outcome, preeclampsia, were not significantly different between groups—occurring in 7.2% of the vitamin group and 6.7% of the placebo group.

Several other studies have found a similar lack of benefit to antioxidant vitamins in terms of altering the risk of hypertension in pregnancy, and the authors suggested several possible explanations.

First, although there is evidence of oxidative stress in preeclampsia, it might not necessarily be important in the pathophysiology of the disease. Or, perhaps it is relevant, but only to a subset of preeclamptic women.

Yet another suggestion was that supplemental vitamin C and E may not be beneficial if women already have adequate concentrations at baseline. It has been suggested that the therapeutic antioxidant window might be between 8 and 10 weeks' gestation at the initiation of intervillous blood flow. However a post hoc subgroup analysis limited to women who were treated before 13 weeks' gestation showed no difference in outcome.

This and other studies have found no benefit of the antioxidant vitamins C and E in altering the risk of hypertension in pregnancy.

Source James E. Reinaker/Elsevier Global Medical News

Major Finding: The rates of preeclampsia were not significantly different between groups, occurring in 7.2% of the women receiving vitamin C and vitamin E and 6.7% of the placebo group.

Data Source: A large multicenter trial of 10,154 low-risk, nulliparous women from 16 clinical centers.

Disclosures: The study was supported by grants from the National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Some of the investigators disclosed financial conflicts.

Daily supplementation with vitamins C and E starting between 9 and 16 weeks' gestation did not reduce the rate of pregnancy-associated hypertension, according to a large multicenter trial in low-risk, nulliparous women.

The findings “provide no support for the use of vitamin C and E supplementation in pregnancy to reduce the risk of preeclampsia or its complications,” wrote Dr. James M. Roberts of the University of Pittsburgh and his colleagues (N. Engl. J. Med. 2010;362:1282-91).

The study randomized 10,154 nulliparous women from 16 clinical centers. All women had singleton pregnancies, with gestational age at randomization ranging between 9 weeks, 0 days and 16 weeks, 6 days. The women were randomly assigned to take 1,000 mg of vitamin C and 400 IU of vitamin E daily, or matching placebo, until the end of their pregnancies. They returned any unused study drug each month and received a new batch, at which time they reported any side effects, and had their blood pressure and urine protein levels measured.

The primary outcome of the study was a composite of pregnancy-associated hypertension and serious adverse outcomes in the mother, fetus, or neonate, while the secondary outcomes included preeclampsia and other maternal and neonatal outcomes.

After some subjects were lost to follow-up or removed, a total of 4,993 women from the vitamin arm and 4,976 from the placebo arm were included in the final analysis.

Neither the primary or secondary outcomes of the study were significantly affected by vitamin treatment. A total of 6.1% of the vitamin group and 5.7% of the placebo group met criteria for the primary outcome. Similarly, the rates of the secondary outcome, preeclampsia, were not significantly different between groups—occurring in 7.2% of the vitamin group and 6.7% of the placebo group.

Several other studies have found a similar lack of benefit to antioxidant vitamins in terms of altering the risk of hypertension in pregnancy, and the authors suggested several possible explanations.

First, although there is evidence of oxidative stress in preeclampsia, it might not necessarily be important in the pathophysiology of the disease. Or, perhaps it is relevant, but only to a subset of preeclamptic women.

Yet another suggestion was that supplemental vitamin C and E may not be beneficial if women already have adequate concentrations at baseline. It has been suggested that the therapeutic antioxidant window might be between 8 and 10 weeks' gestation at the initiation of intervillous blood flow. However a post hoc subgroup analysis limited to women who were treated before 13 weeks' gestation showed no difference in outcome.

This and other studies have found no benefit of the antioxidant vitamins C and E in altering the risk of hypertension in pregnancy.

Source James E. Reinaker/Elsevier Global Medical News

Major Finding: The rates of preeclampsia were not significantly different between groups, occurring in 7.2% of the women receiving vitamin C and vitamin E and 6.7% of the placebo group.

Data Source: A large multicenter trial of 10,154 low-risk, nulliparous women from 16 clinical centers.

Disclosures: The study was supported by grants from the National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Some of the investigators disclosed financial conflicts.

Daily supplementation with vitamins C and E starting between 9 and 16 weeks' gestation did not reduce the rate of pregnancy-associated hypertension, according to a large multicenter trial in low-risk, nulliparous women.

The findings “provide no support for the use of vitamin C and E supplementation in pregnancy to reduce the risk of preeclampsia or its complications,” wrote Dr. James M. Roberts of the University of Pittsburgh and his colleagues (N. Engl. J. Med. 2010;362:1282-91).

The study randomized 10,154 nulliparous women from 16 clinical centers. All women had singleton pregnancies, with gestational age at randomization ranging between 9 weeks, 0 days and 16 weeks, 6 days. The women were randomly assigned to take 1,000 mg of vitamin C and 400 IU of vitamin E daily, or matching placebo, until the end of their pregnancies. They returned any unused study drug each month and received a new batch, at which time they reported any side effects, and had their blood pressure and urine protein levels measured.

The primary outcome of the study was a composite of pregnancy-associated hypertension and serious adverse outcomes in the mother, fetus, or neonate, while the secondary outcomes included preeclampsia and other maternal and neonatal outcomes.

After some subjects were lost to follow-up or removed, a total of 4,993 women from the vitamin arm and 4,976 from the placebo arm were included in the final analysis.

Neither the primary or secondary outcomes of the study were significantly affected by vitamin treatment. A total of 6.1% of the vitamin group and 5.7% of the placebo group met criteria for the primary outcome. Similarly, the rates of the secondary outcome, preeclampsia, were not significantly different between groups—occurring in 7.2% of the vitamin group and 6.7% of the placebo group.

Several other studies have found a similar lack of benefit to antioxidant vitamins in terms of altering the risk of hypertension in pregnancy, and the authors suggested several possible explanations.

First, although there is evidence of oxidative stress in preeclampsia, it might not necessarily be important in the pathophysiology of the disease. Or, perhaps it is relevant, but only to a subset of preeclamptic women.

Yet another suggestion was that supplemental vitamin C and E may not be beneficial if women already have adequate concentrations at baseline. It has been suggested that the therapeutic antioxidant window might be between 8 and 10 weeks' gestation at the initiation of intervillous blood flow. However a post hoc subgroup analysis limited to women who were treated before 13 weeks' gestation showed no difference in outcome.

This and other studies have found no benefit of the antioxidant vitamins C and E in altering the risk of hypertension in pregnancy.

Source James E. Reinaker/Elsevier Global Medical News

Hyperglycemia after myocardial infarction is a red flag for nondiabetic patients about to undergo coronary angiography because it is a risk factor for contrast-induced acute kidney injury, according to a large, retrospective analysis study.

“Hyperglycemic patients without known diabetes should be recognized as a high-risk group for CI-AKI [contrast-induced acute kidney injury] and should be considered for prophylactic measures similar to those used in other high-risk patients,” wrote Dr. Joshua M. Stolker of the Mid American Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and colleagues (J. Am. Coll. Cardiol. 2010;55:1433–40).

The study is the first to document an increasing risk of CI-AKI with progressive blood glucose elevations in patients who do not have diabetes, Dr. Martin A. Alpert and Dr. Carl Carlino of the division of cardiovascular medicine, University of Missouri, Columbia, noted in an editorial (J. Am. Coll. Cardiol. 2010;55:1441–3). “Hyperglycemia … occurs in more than 40% of patients without diabetes with acute myocardial infarction. In the critical care population, hyperglycemia in patients without diabetes is seen by some as a 'stress test' denoting the failure of endogenous insulin reserves to adequately control blood glucose.”

The study analyzed 6,358 consecutive patients from the Health Facts database who underwent coronary angiography after acute MI. Of them, 1,929 (30%) had known diabetes. Preprocedural hyperglycemia (blood glucose at least 140 mg/dL) was present in 42% of the entire cohort, of whom 48% were nondiabetic. All patients were stratified according to their preprocedural blood glucose level: less than 110 mg/dL; 110 to less than 140 mg/dL; 140 to less than 170 mg/dL; 170 to less than 200 mg/dL; and 200 mg/dL or more.

After coronary angiography, 823 patients (13%) developed CI-AKI (an absolute serum creatinine increase of 0.3 mg/dL or more, or a relative increase in serum creatinine of 50% or more within 48 hours of the procedure), the primary study end point. After adjustment for confounders, there was a strong association between preprocedural glucose levels and CI-AKI risk in patients without diabetes, but not in patients with established diabetes—regardless of their glucose levels, reported the authors.

Among the nondiabetic patients, the risk for CI-AKI increased with increasing glucose levels. Compared with patients with blood glucose levels below 100 mg/dL (reference), those in the higher glucose categories had increasingly higher risks for CI-AKI, with odds ratios of 1.31, 1.51, 1.58, and 2.14, all significant differences. This pattern was not seen in diabetic patients (OR 0.71, 0.82, 0.73, 0.94).

Nondiabetic, hyperglycemic acute MI patients may receive less aggressive glucose control than their diabetic counterparts, and may also receive less aggressive CI-AKI prophylaxis, the authors said. Additionally, some hyperglycemic patients may have undiagnosed and untreated diabetes, putting them at higher risk. Also, nondiabetic patients who become hyperglycemic may be experiencing more severe illness compared with diabetes patients who become hyperglycemic.

The results identify a new risk marker and “raise the question of whether interventions such as intensive insulin therapy might reduce risk in this population,” noted the editorialists.

The American Heart Association funded the research. Dr. Stolker has financial ties with AstraZeneca Pharmaceuticals, Pfizer Pharmaceuticals, and Novo Nordisk, and Educational Testing Consultants LLC.

Hyperglycemia after myocardial infarction is a red flag for nondiabetic patients about to undergo coronary angiography because it is a risk factor for contrast-induced acute kidney injury, according to a large, retrospective analysis study.

“Hyperglycemic patients without known diabetes should be recognized as a high-risk group for CI-AKI [contrast-induced acute kidney injury] and should be considered for prophylactic measures similar to those used in other high-risk patients,” wrote Dr. Joshua M. Stolker of the Mid American Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and colleagues (J. Am. Coll. Cardiol. 2010;55:1433–40).

The study is the first to document an increasing risk of CI-AKI with progressive blood glucose elevations in patients who do not have diabetes, Dr. Martin A. Alpert and Dr. Carl Carlino of the division of cardiovascular medicine, University of Missouri, Columbia, noted in an editorial (J. Am. Coll. Cardiol. 2010;55:1441–3). “Hyperglycemia … occurs in more than 40% of patients without diabetes with acute myocardial infarction. In the critical care population, hyperglycemia in patients without diabetes is seen by some as a 'stress test' denoting the failure of endogenous insulin reserves to adequately control blood glucose.”

The study analyzed 6,358 consecutive patients from the Health Facts database who underwent coronary angiography after acute MI. Of them, 1,929 (30%) had known diabetes. Preprocedural hyperglycemia (blood glucose at least 140 mg/dL) was present in 42% of the entire cohort, of whom 48% were nondiabetic. All patients were stratified according to their preprocedural blood glucose level: less than 110 mg/dL; 110 to less than 140 mg/dL; 140 to less than 170 mg/dL; 170 to less than 200 mg/dL; and 200 mg/dL or more.

After coronary angiography, 823 patients (13%) developed CI-AKI (an absolute serum creatinine increase of 0.3 mg/dL or more, or a relative increase in serum creatinine of 50% or more within 48 hours of the procedure), the primary study end point. After adjustment for confounders, there was a strong association between preprocedural glucose levels and CI-AKI risk in patients without diabetes, but not in patients with established diabetes—regardless of their glucose levels, reported the authors.

Among the nondiabetic patients, the risk for CI-AKI increased with increasing glucose levels. Compared with patients with blood glucose levels below 100 mg/dL (reference), those in the higher glucose categories had increasingly higher risks for CI-AKI, with odds ratios of 1.31, 1.51, 1.58, and 2.14, all significant differences. This pattern was not seen in diabetic patients (OR 0.71, 0.82, 0.73, 0.94).

Nondiabetic, hyperglycemic acute MI patients may receive less aggressive glucose control than their diabetic counterparts, and may also receive less aggressive CI-AKI prophylaxis, the authors said. Additionally, some hyperglycemic patients may have undiagnosed and untreated diabetes, putting them at higher risk. Also, nondiabetic patients who become hyperglycemic may be experiencing more severe illness compared with diabetes patients who become hyperglycemic.

The results identify a new risk marker and “raise the question of whether interventions such as intensive insulin therapy might reduce risk in this population,” noted the editorialists.

The American Heart Association funded the research. Dr. Stolker has financial ties with AstraZeneca Pharmaceuticals, Pfizer Pharmaceuticals, and Novo Nordisk, and Educational Testing Consultants LLC.

Hyperglycemia after myocardial infarction is a red flag for nondiabetic patients about to undergo coronary angiography because it is a risk factor for contrast-induced acute kidney injury, according to a large, retrospective analysis study.

“Hyperglycemic patients without known diabetes should be recognized as a high-risk group for CI-AKI [contrast-induced acute kidney injury] and should be considered for prophylactic measures similar to those used in other high-risk patients,” wrote Dr. Joshua M. Stolker of the Mid American Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and colleagues (J. Am. Coll. Cardiol. 2010;55:1433–40).

The study is the first to document an increasing risk of CI-AKI with progressive blood glucose elevations in patients who do not have diabetes, Dr. Martin A. Alpert and Dr. Carl Carlino of the division of cardiovascular medicine, University of Missouri, Columbia, noted in an editorial (J. Am. Coll. Cardiol. 2010;55:1441–3). “Hyperglycemia … occurs in more than 40% of patients without diabetes with acute myocardial infarction. In the critical care population, hyperglycemia in patients without diabetes is seen by some as a 'stress test' denoting the failure of endogenous insulin reserves to adequately control blood glucose.”

The study analyzed 6,358 consecutive patients from the Health Facts database who underwent coronary angiography after acute MI. Of them, 1,929 (30%) had known diabetes. Preprocedural hyperglycemia (blood glucose at least 140 mg/dL) was present in 42% of the entire cohort, of whom 48% were nondiabetic. All patients were stratified according to their preprocedural blood glucose level: less than 110 mg/dL; 110 to less than 140 mg/dL; 140 to less than 170 mg/dL; 170 to less than 200 mg/dL; and 200 mg/dL or more.

After coronary angiography, 823 patients (13%) developed CI-AKI (an absolute serum creatinine increase of 0.3 mg/dL or more, or a relative increase in serum creatinine of 50% or more within 48 hours of the procedure), the primary study end point. After adjustment for confounders, there was a strong association between preprocedural glucose levels and CI-AKI risk in patients without diabetes, but not in patients with established diabetes—regardless of their glucose levels, reported the authors.

Among the nondiabetic patients, the risk for CI-AKI increased with increasing glucose levels. Compared with patients with blood glucose levels below 100 mg/dL (reference), those in the higher glucose categories had increasingly higher risks for CI-AKI, with odds ratios of 1.31, 1.51, 1.58, and 2.14, all significant differences. This pattern was not seen in diabetic patients (OR 0.71, 0.82, 0.73, 0.94).

Nondiabetic, hyperglycemic acute MI patients may receive less aggressive glucose control than their diabetic counterparts, and may also receive less aggressive CI-AKI prophylaxis, the authors said. Additionally, some hyperglycemic patients may have undiagnosed and untreated diabetes, putting them at higher risk. Also, nondiabetic patients who become hyperglycemic may be experiencing more severe illness compared with diabetes patients who become hyperglycemic.

The results identify a new risk marker and “raise the question of whether interventions such as intensive insulin therapy might reduce risk in this population,” noted the editorialists.

The American Heart Association funded the research. Dr. Stolker has financial ties with AstraZeneca Pharmaceuticals, Pfizer Pharmaceuticals, and Novo Nordisk, and Educational Testing Consultants LLC.

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering