Bruce K. Dixon

CHICAGO — Newly issued guidelines seek to standardize valve surgery, improve the quantification of valve lesions, and involve patients in their management.

Released at a meeting sponsored by the American College of Cardiology, the Guidelines for the Management of Patients with Valvular Heart Disease recommend the widespread use of echocardiography and Doppler imaging, according the chairman of the guideline writing committee, Dr. Robert O. Bonow.

The 148-page document is the first revision of the practice guidelines of the ACC and the American Heart Association, originally released in 1998.

“What the guidelines are attempting to do is to move the field into a more objective and quantitative approach, and there are ways to do this with Doppler imaging, which many laboratories are not doing,” said Dr. Bonow, chief of the division of cardiology at Northwestern University in Chicago.

“We do not want echocardiography and Doppler cardiograms being interpreted only qualitatively. If valve regurgitation appears to be severe, it should be measured so that the severity can be quantitatively demonstrated,” he said in an interview.

Committee members who presented the guidelines at the meeting emphasized several issues:

▸ Aortic stenosis. The basic guidelines for aortic stenosis remain largely unchanged, but the revision clarifies the definition of “severe” asymptomatic aortic stenosis and states that adults with this diagnosis may be considered for valve replacement if there is a high likelihood of rapid progression or if surgery might be delayed at the time of symptom onset.

Also new is the recommendation that aortic valve replacement may be considered in patients undergoing coronary artery bypass grafting who have mild AS when there is evidence that progression may be rapid.

When valve replacement is considered, watchful waiting is advised, because there's no evidence in the literature that a benefit can be derived from performing valve replacement in the absence of symptoms, the new guidelines state.

▸ Aortic regurgitation. In recognition of the relatively benign course of lone asymptomatic aortic regurgitation, the committee recommended against valve repair or replacement in patients with normal left ventricular systolic function at rest. “Surgery is reasonable for patients with very large ventricles who may be at risk for sudden cardiac death,” said committee member Dr. Patrick T. O'Gara.

Aortic valve repair or replacement also is indicated for symptomatic patients with severe aortic regurgitation irrespective of left-ventricular systolic function, and in those with severe AR who have a need to undergo cardiac or aortic surgery, explained Dr. O'Gara of the Harvard Medical School in Boston.

▸ Mitral regurgitation. Two themes emerge in the guidelines for mitral regurgitation, emphasizing the need for valve repair and earlier surgery. “The committee is trying to direct the trend more toward valve repair and away from valve replacement,” said committee member Dr. Blase A. Carabello, vice chairman of the department of medicine at the Baylor College of Medicine in Houston, explaining that studies show that repair has survival advantages over replacement.

Another issue involves valve selection—mechanical or bioprosthetic—for those requiring replacement. The cutoff age of 65 for the use of bioprosthetic valves was liberalized to the advantage of younger patients who wish to avoid the use of blood-thinning drugs, Dr. Bonow explained. The patient should understand that, with a bioprosthetic valve, there's a high likelihood of the need for a second operation later on, he stressed.

The guidelines also clarify the use of blood thinners in pregnancy, recommending continuous anticoagulation in all pregnant women with mechanical prosthetic valves. Up to 36 weeks' gestation, the therapeutic choice of continuous dose-adjusted or intravenous subcutaneous unfractionated heparin, dose-adjusted low-molecular-weight heparin, or warfarin should be discussed fully.

The 2006 guidelines can be viewed online at www.acc.orgwww.myamericanheart.org

The guidelines are attempting 'to move the field into a more objective and quantitative approach.' DR. BONOW

CHICAGO — Newly issued guidelines seek to standardize valve surgery, improve the quantification of valve lesions, and involve patients in their management.

Released at a meeting sponsored by the American College of Cardiology, the Guidelines for the Management of Patients with Valvular Heart Disease recommend the widespread use of echocardiography and Doppler imaging, according the chairman of the guideline writing committee, Dr. Robert O. Bonow.

The 148-page document is the first revision of the practice guidelines of the ACC and the American Heart Association, originally released in 1998.

“What the guidelines are attempting to do is to move the field into a more objective and quantitative approach, and there are ways to do this with Doppler imaging, which many laboratories are not doing,” said Dr. Bonow, chief of the division of cardiology at Northwestern University in Chicago.

“We do not want echocardiography and Doppler cardiograms being interpreted only qualitatively. If valve regurgitation appears to be severe, it should be measured so that the severity can be quantitatively demonstrated,” he said in an interview.

Committee members who presented the guidelines at the meeting emphasized several issues:

▸ Aortic stenosis. The basic guidelines for aortic stenosis remain largely unchanged, but the revision clarifies the definition of “severe” asymptomatic aortic stenosis and states that adults with this diagnosis may be considered for valve replacement if there is a high likelihood of rapid progression or if surgery might be delayed at the time of symptom onset.

Also new is the recommendation that aortic valve replacement may be considered in patients undergoing coronary artery bypass grafting who have mild AS when there is evidence that progression may be rapid.

When valve replacement is considered, watchful waiting is advised, because there's no evidence in the literature that a benefit can be derived from performing valve replacement in the absence of symptoms, the new guidelines state.

▸ Aortic regurgitation. In recognition of the relatively benign course of lone asymptomatic aortic regurgitation, the committee recommended against valve repair or replacement in patients with normal left ventricular systolic function at rest. “Surgery is reasonable for patients with very large ventricles who may be at risk for sudden cardiac death,” said committee member Dr. Patrick T. O'Gara.

Aortic valve repair or replacement also is indicated for symptomatic patients with severe aortic regurgitation irrespective of left-ventricular systolic function, and in those with severe AR who have a need to undergo cardiac or aortic surgery, explained Dr. O'Gara of the Harvard Medical School in Boston.

▸ Mitral regurgitation. Two themes emerge in the guidelines for mitral regurgitation, emphasizing the need for valve repair and earlier surgery. “The committee is trying to direct the trend more toward valve repair and away from valve replacement,” said committee member Dr. Blase A. Carabello, vice chairman of the department of medicine at the Baylor College of Medicine in Houston, explaining that studies show that repair has survival advantages over replacement.

Another issue involves valve selection—mechanical or bioprosthetic—for those requiring replacement. The cutoff age of 65 for the use of bioprosthetic valves was liberalized to the advantage of younger patients who wish to avoid the use of blood-thinning drugs, Dr. Bonow explained. The patient should understand that, with a bioprosthetic valve, there's a high likelihood of the need for a second operation later on, he stressed.

The guidelines also clarify the use of blood thinners in pregnancy, recommending continuous anticoagulation in all pregnant women with mechanical prosthetic valves. Up to 36 weeks' gestation, the therapeutic choice of continuous dose-adjusted or intravenous subcutaneous unfractionated heparin, dose-adjusted low-molecular-weight heparin, or warfarin should be discussed fully.

The 2006 guidelines can be viewed online at www.acc.orgwww.myamericanheart.org

The guidelines are attempting 'to move the field into a more objective and quantitative approach.' DR. BONOW

CHICAGO — Newly issued guidelines seek to standardize valve surgery, improve the quantification of valve lesions, and involve patients in their management.

Released at a meeting sponsored by the American College of Cardiology, the Guidelines for the Management of Patients with Valvular Heart Disease recommend the widespread use of echocardiography and Doppler imaging, according the chairman of the guideline writing committee, Dr. Robert O. Bonow.

The 148-page document is the first revision of the practice guidelines of the ACC and the American Heart Association, originally released in 1998.

“What the guidelines are attempting to do is to move the field into a more objective and quantitative approach, and there are ways to do this with Doppler imaging, which many laboratories are not doing,” said Dr. Bonow, chief of the division of cardiology at Northwestern University in Chicago.

“We do not want echocardiography and Doppler cardiograms being interpreted only qualitatively. If valve regurgitation appears to be severe, it should be measured so that the severity can be quantitatively demonstrated,” he said in an interview.

Committee members who presented the guidelines at the meeting emphasized several issues:

▸ Aortic stenosis. The basic guidelines for aortic stenosis remain largely unchanged, but the revision clarifies the definition of “severe” asymptomatic aortic stenosis and states that adults with this diagnosis may be considered for valve replacement if there is a high likelihood of rapid progression or if surgery might be delayed at the time of symptom onset.

Also new is the recommendation that aortic valve replacement may be considered in patients undergoing coronary artery bypass grafting who have mild AS when there is evidence that progression may be rapid.

When valve replacement is considered, watchful waiting is advised, because there's no evidence in the literature that a benefit can be derived from performing valve replacement in the absence of symptoms, the new guidelines state.

▸ Aortic regurgitation. In recognition of the relatively benign course of lone asymptomatic aortic regurgitation, the committee recommended against valve repair or replacement in patients with normal left ventricular systolic function at rest. “Surgery is reasonable for patients with very large ventricles who may be at risk for sudden cardiac death,” said committee member Dr. Patrick T. O'Gara.

Aortic valve repair or replacement also is indicated for symptomatic patients with severe aortic regurgitation irrespective of left-ventricular systolic function, and in those with severe AR who have a need to undergo cardiac or aortic surgery, explained Dr. O'Gara of the Harvard Medical School in Boston.

▸ Mitral regurgitation. Two themes emerge in the guidelines for mitral regurgitation, emphasizing the need for valve repair and earlier surgery. “The committee is trying to direct the trend more toward valve repair and away from valve replacement,” said committee member Dr. Blase A. Carabello, vice chairman of the department of medicine at the Baylor College of Medicine in Houston, explaining that studies show that repair has survival advantages over replacement.

Another issue involves valve selection—mechanical or bioprosthetic—for those requiring replacement. The cutoff age of 65 for the use of bioprosthetic valves was liberalized to the advantage of younger patients who wish to avoid the use of blood-thinning drugs, Dr. Bonow explained. The patient should understand that, with a bioprosthetic valve, there's a high likelihood of the need for a second operation later on, he stressed.

The guidelines also clarify the use of blood thinners in pregnancy, recommending continuous anticoagulation in all pregnant women with mechanical prosthetic valves. Up to 36 weeks' gestation, the therapeutic choice of continuous dose-adjusted or intravenous subcutaneous unfractionated heparin, dose-adjusted low-molecular-weight heparin, or warfarin should be discussed fully.

The 2006 guidelines can be viewed online at www.acc.orgwww.myamericanheart.org

The guidelines are attempting 'to move the field into a more objective and quantitative approach.' DR. BONOW

LA JOLLA, CALIF. — It's time to rekindle enthusiasm for postmenopausal hormone therapy, Dr. Leon Speroff said at the annual meeting of the Association of Reproductive Health Professionals. “In my view, postmenopausal hormone therapy is in a stalled position and it's time to move forward,” said Dr. Speroff, professor of obstetrics and gynecology and reproductive endocrinology at Oregon Health and Science University, Portland.

“The initial negative impact of the Women's Health Initiative is over, we know the study's limitations, we know that some of the conclusions promoted in the media were not correct, and we know that the risks that have been promoted by the Women's Health Initiative are incredibly small and perhaps not real,” Dr. Speroff said in an interview.

Dr. Speroff pointed out several problems surrounding the WHI, including diagnostic and selection biases, high drop-in and drop-out rates, poorly presented media reports, sound-bite interpretations by “experts,” epidemiologists giving clinical advice, and the writing of position papers by various medical organizations that, in Dr. Speroff's opinion, “were profoundly influenced by medical-legal fears.”

While data from the WHI suggested that estrogen with progestin increased the risk of breast cancer, Dr. Speroff said that he believes the therapy may actually be beneficial when used early in menopause. He said that his suspicion was fueled by paradoxical findings from worldwide observational studies showing that while hormone users had an increased risk of breast cancer, they had reduced risk of mortality.

One explanation was that hormone users had more mammograms and their cancers were detected earlier. Subsequent studies corrected for this, looking only at women who were having mammography, and reports emerged documenting that estrogen-receptor positive hormone users who developed breast cancer had lower-stage, lower-grade disease, said Dr. Speroff, a consultant with Warner Chilcott, which markets Femtrace, and a recipient of research grants from Wyeth, Organon USA Inc., and Barr Laboratories Inc. “That struck me as the answer to the apparent paradox … that what we are seeing is earlier detection of less-aggressive disease, and thus the tumors of hormone users have better outcomes.”

However, surgeons at the University of Utah, Salt Lake City, have given Dr. Speroff a different explanation: “They argued that mammography doesn't detect the tumor itself … that imaging detects the stromal reaction around the tumor and … that hormone exposure causes differentiation of the tumor and slower growth, allowing more time for the stromal reaction and thus earlier detection.”

In any case, he added, both explanations add up to earlier detection. “All the studies find the increased risk fast, and it takes about 10 years for a malignant breast cell to become clinically detectable. Every single study has found the increased risk only in current users. After discontinuation, the risk returns to baseline and, to this day, not a single study has found an increase in hormone users in noninvasive, in situ disease,” Dr. Speroff said at the meeting.

Dr. Speroff added that the latest report on breast cancer from the WHI was issued this summer, and for the first time, all of the risk factors that influenced breast cancer had been taken into account and adjustments had been made. “The increased overall risk of breast cancer in the canceled estrogen-progestin arm after adjustments is no longer statistically significant,” said Dr. Speroff, adding that in the updated results, patients who adhered to treatment throughout the study had a significant reduction in the risk of breast cancer.

Physicians are warned, however, not to automatically conclude that the difference in results in the two arms reflects the effect of progestational agents, because the participants in the two arms were not identical.

“In terms of both cardiovascular disease and breast cancer, there are major differences comparing the two arms, and therefore it's not appropriate to conclude that the difference represents a progestational effect,” he said. “So where we are today with breast cancer is we're not sure whether there truly is an increased risk or whether we're seeing an impact on preexisting tumors, and the possibility remains that exposure to estrogen and progestin may actually be beneficial, causing greater differentiation and earlier detection and better outcomes.”

Dr. Speroff continued, “I tell clinicians that until we have definitive randomized trial data—which we may never have—whatever the patient wants to do is the correct decision. It takes about 10 minutes talking to a patient to know what she wants. However, it's important to point out to her that in case series involving over a thousand patients, whether your tumor receptor was positive or negative, it didn't make any difference.”

Out of the controversy over the link between hormone therapy and coronary heart disease (CHD) there has emerged a theme, or hypothesis, that it takes healthy cardiovascular endothelium to have a maximal beneficial response to estrogen exposure, continued Dr. Speroff.

For example, in the Nurse's Health Study, which looked at conjugated equine estrogens plus medroxyprogesterone acetate vs. placebo in more than 1,660 women, the only statistically significant reduction in CHD occurred in women who began estrogen early in their postmenopausal years, with no difference between the two treatment arms, he said.

At adjudication of WHI data, Dr. Speroff added, 10% of the coronary diagnoses were changed and CHD was no longer statistically significant—facts he said received no publicity whatsoever. “The only significant increase in coronary events in the WHI estrogen-progestin arm occurred in the women who were 20 or more years away from menopause; these were the oldest women in the study [N. Engl. J. Med. 2003;349:523]. When you subtract that group of women, there was no increase in coronary events … and after adjudication there was no increase in coronary disease in the estrogen-only arm [Arch. Intern. Med. 2006;166:357]. The WHI reported this as no beneficial effect, but if you read the report carefully, I believe you can find supporting evidence for a primary prevention effect” from hormone replacement.

Dr. Speroff concluded, “If there's one thing that's not going to change in coming years, it's the media, and it's time we become active in objecting to this policy where the major journals provide the publications to the media before they become available to you and me and the public. It's time that, as organizations and individuals, we begin to protest this particular policy.”

Dr. Steven Goldstein, who described himself as being “in the middle” on the issue of hormone therapy, agreed with Dr. Speroff.

“Some major journals [reporting WHI data] were in a frenzy to get air time,” Dr. Goldstein, professor of obstetrics and gynecology at New York University, said in an interview. Broadly speaking, reporting on the initiative represented a failure to educate the public on the difference between relative and absolute risk, he said.

“In this era of evidence-based medicine, people glom onto the randomized, controlled trial as being the gold standard of clinical evidence, and it should be. However, if you do that, you'd better be sure that the patient sitting opposite you in the consult room is exactly like the women in the study; otherwise, the results are not necessarily relevant,” he said.

“However, what Dr. Speroff has done I think is try to reslice the deck and reanalyze the statistics, which is no more valid than what he's accusing the WHI of doing,” said Dr. Goldstein, adding that he would rather get patients and physicians to recognize that “the 51-year-old woman who has 15 hot flashes a day and can't sleep can be helped with preparations that are not the same as those tested in the WHI, and that extrapolation from the WHI is unfair and inappropriate.”

Dr. Goldstein added that the information coming out of adjudication is not very valuable if suddenly “there's one less case so it's not statistically significant, or one more case and it is. That's tenuous information when you have thousands of people involved and people are fallible; so you're obviously dealing with a situation that is not clear cut.”

He said that the “pretty significant difference between the two arms of the WHI study” supports an epidemiologic study of over 46,000 postmenopausal women, in which those taking estrogen plus progestin were at greater risk for breast cancer compared with women taking estrogen alone (JAMA 2000;283:485–91).

“And the Million-Women study in England, whose flaws were somewhat overcome by the sheer number of women involved, showed three times as much breast cancer with estrogen plus progestin as with estrogen alone. And that wasn't just Prempro; that was any formulation,” Dr. Goldstein explained (Lancet 2003;362:419–27), adding that women are being overtreated with progestogen in an attempt to prevent uterine cancer. “If you look at the literature, unopposed Premarin for 6 months results in simple hyperplasia in 7% of women. We're treating 100% of women with a uterus to protect seven.”

Dr. Speroff's proposition that hormone therapy may actually protect women by causing greater differentiation and earlier detection “is an incredibly interesting hypothesis, but I can't in good conscience tell my patients that they should therefore take hormone therapy because if they're destined to get breast cancer this is going to make early detection more likely and improve their survival. I hope that's true, but it's not going to be my motivation for hormone therapy,” Dr. Goldstein said.

When asked to comment on Dr. Speroff's presentation, Dr. Wulf H. Utian, president of the North American Menopause Society, said, “In many ways I agree with what Dr. Speroff says. As huge as the WHI was, it was not a gold standard study. The bottom line is that we really need to be more reasonable and less emotional about hormone therapy.”

LA JOLLA, CALIF. — It's time to rekindle enthusiasm for postmenopausal hormone therapy, Dr. Leon Speroff said at the annual meeting of the Association of Reproductive Health Professionals. “In my view, postmenopausal hormone therapy is in a stalled position and it's time to move forward,” said Dr. Speroff, professor of obstetrics and gynecology and reproductive endocrinology at Oregon Health and Science University, Portland.

“The initial negative impact of the Women's Health Initiative is over, we know the study's limitations, we know that some of the conclusions promoted in the media were not correct, and we know that the risks that have been promoted by the Women's Health Initiative are incredibly small and perhaps not real,” Dr. Speroff said in an interview.

Dr. Speroff pointed out several problems surrounding the WHI, including diagnostic and selection biases, high drop-in and drop-out rates, poorly presented media reports, sound-bite interpretations by “experts,” epidemiologists giving clinical advice, and the writing of position papers by various medical organizations that, in Dr. Speroff's opinion, “were profoundly influenced by medical-legal fears.”

While data from the WHI suggested that estrogen with progestin increased the risk of breast cancer, Dr. Speroff said that he believes the therapy may actually be beneficial when used early in menopause. He said that his suspicion was fueled by paradoxical findings from worldwide observational studies showing that while hormone users had an increased risk of breast cancer, they had reduced risk of mortality.

One explanation was that hormone users had more mammograms and their cancers were detected earlier. Subsequent studies corrected for this, looking only at women who were having mammography, and reports emerged documenting that estrogen-receptor positive hormone users who developed breast cancer had lower-stage, lower-grade disease, said Dr. Speroff, a consultant with Warner Chilcott, which markets Femtrace, and a recipient of research grants from Wyeth, Organon USA Inc., and Barr Laboratories Inc. “That struck me as the answer to the apparent paradox … that what we are seeing is earlier detection of less-aggressive disease, and thus the tumors of hormone users have better outcomes.”

However, surgeons at the University of Utah, Salt Lake City, have given Dr. Speroff a different explanation: “They argued that mammography doesn't detect the tumor itself … that imaging detects the stromal reaction around the tumor and … that hormone exposure causes differentiation of the tumor and slower growth, allowing more time for the stromal reaction and thus earlier detection.”

In any case, he added, both explanations add up to earlier detection. “All the studies find the increased risk fast, and it takes about 10 years for a malignant breast cell to become clinically detectable. Every single study has found the increased risk only in current users. After discontinuation, the risk returns to baseline and, to this day, not a single study has found an increase in hormone users in noninvasive, in situ disease,” Dr. Speroff said at the meeting.

Dr. Speroff added that the latest report on breast cancer from the WHI was issued this summer, and for the first time, all of the risk factors that influenced breast cancer had been taken into account and adjustments had been made. “The increased overall risk of breast cancer in the canceled estrogen-progestin arm after adjustments is no longer statistically significant,” said Dr. Speroff, adding that in the updated results, patients who adhered to treatment throughout the study had a significant reduction in the risk of breast cancer.

Physicians are warned, however, not to automatically conclude that the difference in results in the two arms reflects the effect of progestational agents, because the participants in the two arms were not identical.

“In terms of both cardiovascular disease and breast cancer, there are major differences comparing the two arms, and therefore it's not appropriate to conclude that the difference represents a progestational effect,” he said. “So where we are today with breast cancer is we're not sure whether there truly is an increased risk or whether we're seeing an impact on preexisting tumors, and the possibility remains that exposure to estrogen and progestin may actually be beneficial, causing greater differentiation and earlier detection and better outcomes.”

Dr. Speroff continued, “I tell clinicians that until we have definitive randomized trial data—which we may never have—whatever the patient wants to do is the correct decision. It takes about 10 minutes talking to a patient to know what she wants. However, it's important to point out to her that in case series involving over a thousand patients, whether your tumor receptor was positive or negative, it didn't make any difference.”

Out of the controversy over the link between hormone therapy and coronary heart disease (CHD) there has emerged a theme, or hypothesis, that it takes healthy cardiovascular endothelium to have a maximal beneficial response to estrogen exposure, continued Dr. Speroff.

For example, in the Nurse's Health Study, which looked at conjugated equine estrogens plus medroxyprogesterone acetate vs. placebo in more than 1,660 women, the only statistically significant reduction in CHD occurred in women who began estrogen early in their postmenopausal years, with no difference between the two treatment arms, he said.

At adjudication of WHI data, Dr. Speroff added, 10% of the coronary diagnoses were changed and CHD was no longer statistically significant—facts he said received no publicity whatsoever. “The only significant increase in coronary events in the WHI estrogen-progestin arm occurred in the women who were 20 or more years away from menopause; these were the oldest women in the study [N. Engl. J. Med. 2003;349:523]. When you subtract that group of women, there was no increase in coronary events … and after adjudication there was no increase in coronary disease in the estrogen-only arm [Arch. Intern. Med. 2006;166:357]. The WHI reported this as no beneficial effect, but if you read the report carefully, I believe you can find supporting evidence for a primary prevention effect” from hormone replacement.

Dr. Speroff concluded, “If there's one thing that's not going to change in coming years, it's the media, and it's time we become active in objecting to this policy where the major journals provide the publications to the media before they become available to you and me and the public. It's time that, as organizations and individuals, we begin to protest this particular policy.”

Dr. Steven Goldstein, who described himself as being “in the middle” on the issue of hormone therapy, agreed with Dr. Speroff.

“Some major journals [reporting WHI data] were in a frenzy to get air time,” Dr. Goldstein, professor of obstetrics and gynecology at New York University, said in an interview. Broadly speaking, reporting on the initiative represented a failure to educate the public on the difference between relative and absolute risk, he said.

“In this era of evidence-based medicine, people glom onto the randomized, controlled trial as being the gold standard of clinical evidence, and it should be. However, if you do that, you'd better be sure that the patient sitting opposite you in the consult room is exactly like the women in the study; otherwise, the results are not necessarily relevant,” he said.

“However, what Dr. Speroff has done I think is try to reslice the deck and reanalyze the statistics, which is no more valid than what he's accusing the WHI of doing,” said Dr. Goldstein, adding that he would rather get patients and physicians to recognize that “the 51-year-old woman who has 15 hot flashes a day and can't sleep can be helped with preparations that are not the same as those tested in the WHI, and that extrapolation from the WHI is unfair and inappropriate.”

Dr. Goldstein added that the information coming out of adjudication is not very valuable if suddenly “there's one less case so it's not statistically significant, or one more case and it is. That's tenuous information when you have thousands of people involved and people are fallible; so you're obviously dealing with a situation that is not clear cut.”

He said that the “pretty significant difference between the two arms of the WHI study” supports an epidemiologic study of over 46,000 postmenopausal women, in which those taking estrogen plus progestin were at greater risk for breast cancer compared with women taking estrogen alone (JAMA 2000;283:485–91).

“And the Million-Women study in England, whose flaws were somewhat overcome by the sheer number of women involved, showed three times as much breast cancer with estrogen plus progestin as with estrogen alone. And that wasn't just Prempro; that was any formulation,” Dr. Goldstein explained (Lancet 2003;362:419–27), adding that women are being overtreated with progestogen in an attempt to prevent uterine cancer. “If you look at the literature, unopposed Premarin for 6 months results in simple hyperplasia in 7% of women. We're treating 100% of women with a uterus to protect seven.”

Dr. Speroff's proposition that hormone therapy may actually protect women by causing greater differentiation and earlier detection “is an incredibly interesting hypothesis, but I can't in good conscience tell my patients that they should therefore take hormone therapy because if they're destined to get breast cancer this is going to make early detection more likely and improve their survival. I hope that's true, but it's not going to be my motivation for hormone therapy,” Dr. Goldstein said.

When asked to comment on Dr. Speroff's presentation, Dr. Wulf H. Utian, president of the North American Menopause Society, said, “In many ways I agree with what Dr. Speroff says. As huge as the WHI was, it was not a gold standard study. The bottom line is that we really need to be more reasonable and less emotional about hormone therapy.”

LA JOLLA, CALIF. — It's time to rekindle enthusiasm for postmenopausal hormone therapy, Dr. Leon Speroff said at the annual meeting of the Association of Reproductive Health Professionals. “In my view, postmenopausal hormone therapy is in a stalled position and it's time to move forward,” said Dr. Speroff, professor of obstetrics and gynecology and reproductive endocrinology at Oregon Health and Science University, Portland.

“The initial negative impact of the Women's Health Initiative is over, we know the study's limitations, we know that some of the conclusions promoted in the media were not correct, and we know that the risks that have been promoted by the Women's Health Initiative are incredibly small and perhaps not real,” Dr. Speroff said in an interview.

Dr. Speroff pointed out several problems surrounding the WHI, including diagnostic and selection biases, high drop-in and drop-out rates, poorly presented media reports, sound-bite interpretations by “experts,” epidemiologists giving clinical advice, and the writing of position papers by various medical organizations that, in Dr. Speroff's opinion, “were profoundly influenced by medical-legal fears.”

While data from the WHI suggested that estrogen with progestin increased the risk of breast cancer, Dr. Speroff said that he believes the therapy may actually be beneficial when used early in menopause. He said that his suspicion was fueled by paradoxical findings from worldwide observational studies showing that while hormone users had an increased risk of breast cancer, they had reduced risk of mortality.

One explanation was that hormone users had more mammograms and their cancers were detected earlier. Subsequent studies corrected for this, looking only at women who were having mammography, and reports emerged documenting that estrogen-receptor positive hormone users who developed breast cancer had lower-stage, lower-grade disease, said Dr. Speroff, a consultant with Warner Chilcott, which markets Femtrace, and a recipient of research grants from Wyeth, Organon USA Inc., and Barr Laboratories Inc. “That struck me as the answer to the apparent paradox … that what we are seeing is earlier detection of less-aggressive disease, and thus the tumors of hormone users have better outcomes.”

However, surgeons at the University of Utah, Salt Lake City, have given Dr. Speroff a different explanation: “They argued that mammography doesn't detect the tumor itself … that imaging detects the stromal reaction around the tumor and … that hormone exposure causes differentiation of the tumor and slower growth, allowing more time for the stromal reaction and thus earlier detection.”

In any case, he added, both explanations add up to earlier detection. “All the studies find the increased risk fast, and it takes about 10 years for a malignant breast cell to become clinically detectable. Every single study has found the increased risk only in current users. After discontinuation, the risk returns to baseline and, to this day, not a single study has found an increase in hormone users in noninvasive, in situ disease,” Dr. Speroff said at the meeting.

Dr. Speroff added that the latest report on breast cancer from the WHI was issued this summer, and for the first time, all of the risk factors that influenced breast cancer had been taken into account and adjustments had been made. “The increased overall risk of breast cancer in the canceled estrogen-progestin arm after adjustments is no longer statistically significant,” said Dr. Speroff, adding that in the updated results, patients who adhered to treatment throughout the study had a significant reduction in the risk of breast cancer.

Physicians are warned, however, not to automatically conclude that the difference in results in the two arms reflects the effect of progestational agents, because the participants in the two arms were not identical.

“In terms of both cardiovascular disease and breast cancer, there are major differences comparing the two arms, and therefore it's not appropriate to conclude that the difference represents a progestational effect,” he said. “So where we are today with breast cancer is we're not sure whether there truly is an increased risk or whether we're seeing an impact on preexisting tumors, and the possibility remains that exposure to estrogen and progestin may actually be beneficial, causing greater differentiation and earlier detection and better outcomes.”

Dr. Speroff continued, “I tell clinicians that until we have definitive randomized trial data—which we may never have—whatever the patient wants to do is the correct decision. It takes about 10 minutes talking to a patient to know what she wants. However, it's important to point out to her that in case series involving over a thousand patients, whether your tumor receptor was positive or negative, it didn't make any difference.”

Out of the controversy over the link between hormone therapy and coronary heart disease (CHD) there has emerged a theme, or hypothesis, that it takes healthy cardiovascular endothelium to have a maximal beneficial response to estrogen exposure, continued Dr. Speroff.

For example, in the Nurse's Health Study, which looked at conjugated equine estrogens plus medroxyprogesterone acetate vs. placebo in more than 1,660 women, the only statistically significant reduction in CHD occurred in women who began estrogen early in their postmenopausal years, with no difference between the two treatment arms, he said.

At adjudication of WHI data, Dr. Speroff added, 10% of the coronary diagnoses were changed and CHD was no longer statistically significant—facts he said received no publicity whatsoever. “The only significant increase in coronary events in the WHI estrogen-progestin arm occurred in the women who were 20 or more years away from menopause; these were the oldest women in the study [N. Engl. J. Med. 2003;349:523]. When you subtract that group of women, there was no increase in coronary events … and after adjudication there was no increase in coronary disease in the estrogen-only arm [Arch. Intern. Med. 2006;166:357]. The WHI reported this as no beneficial effect, but if you read the report carefully, I believe you can find supporting evidence for a primary prevention effect” from hormone replacement.

Dr. Speroff concluded, “If there's one thing that's not going to change in coming years, it's the media, and it's time we become active in objecting to this policy where the major journals provide the publications to the media before they become available to you and me and the public. It's time that, as organizations and individuals, we begin to protest this particular policy.”

Dr. Steven Goldstein, who described himself as being “in the middle” on the issue of hormone therapy, agreed with Dr. Speroff.

“Some major journals [reporting WHI data] were in a frenzy to get air time,” Dr. Goldstein, professor of obstetrics and gynecology at New York University, said in an interview. Broadly speaking, reporting on the initiative represented a failure to educate the public on the difference between relative and absolute risk, he said.

“In this era of evidence-based medicine, people glom onto the randomized, controlled trial as being the gold standard of clinical evidence, and it should be. However, if you do that, you'd better be sure that the patient sitting opposite you in the consult room is exactly like the women in the study; otherwise, the results are not necessarily relevant,” he said.

“However, what Dr. Speroff has done I think is try to reslice the deck and reanalyze the statistics, which is no more valid than what he's accusing the WHI of doing,” said Dr. Goldstein, adding that he would rather get patients and physicians to recognize that “the 51-year-old woman who has 15 hot flashes a day and can't sleep can be helped with preparations that are not the same as those tested in the WHI, and that extrapolation from the WHI is unfair and inappropriate.”

Dr. Goldstein added that the information coming out of adjudication is not very valuable if suddenly “there's one less case so it's not statistically significant, or one more case and it is. That's tenuous information when you have thousands of people involved and people are fallible; so you're obviously dealing with a situation that is not clear cut.”

He said that the “pretty significant difference between the two arms of the WHI study” supports an epidemiologic study of over 46,000 postmenopausal women, in which those taking estrogen plus progestin were at greater risk for breast cancer compared with women taking estrogen alone (JAMA 2000;283:485–91).

“And the Million-Women study in England, whose flaws were somewhat overcome by the sheer number of women involved, showed three times as much breast cancer with estrogen plus progestin as with estrogen alone. And that wasn't just Prempro; that was any formulation,” Dr. Goldstein explained (Lancet 2003;362:419–27), adding that women are being overtreated with progestogen in an attempt to prevent uterine cancer. “If you look at the literature, unopposed Premarin for 6 months results in simple hyperplasia in 7% of women. We're treating 100% of women with a uterus to protect seven.”

Dr. Speroff's proposition that hormone therapy may actually protect women by causing greater differentiation and earlier detection “is an incredibly interesting hypothesis, but I can't in good conscience tell my patients that they should therefore take hormone therapy because if they're destined to get breast cancer this is going to make early detection more likely and improve their survival. I hope that's true, but it's not going to be my motivation for hormone therapy,” Dr. Goldstein said.

When asked to comment on Dr. Speroff's presentation, Dr. Wulf H. Utian, president of the North American Menopause Society, said, “In many ways I agree with what Dr. Speroff says. As huge as the WHI was, it was not a gold standard study. The bottom line is that we really need to be more reasonable and less emotional about hormone therapy.”

A nationwide population-based study suggests that the rate of complications 6 months after bariatric surgery is higher than previous research suggested, and that resultant hospital readmissions increase health care costs.

“A clear way to reduce the costs and improve outcomes of bariatric surgery is to address the high rate of postoperative complications,” said William E. Encinosa, Ph.D., and his colleagues at the Agency for Healthcare Research and Quality in Rockville, Md.

The study of insurance claims data across 49 states in 2001 and 2002 found that nearly 40% of bariatric surgery patients experienced a complication within 180 days of being discharged, while 22% of patients had a complication prior to discharge (Medical Care 2006;44:706–12). That represents an 81% increase in complications over the 6 months after surgery, compared with the 10%–20% range found in the literature, the authors said.

The five most common complications were dumping syndrome (19.5%), complications of the anastomosis (12.3%), abdominal hernia (7%), infection (5.7%), and pneumonia (4.1%).

However, the study is weakened by its reliance on claims data, Dr. Matthew M. Hutter said in an interview. “Reliance on claim forms data makes it difficult to determine what a complication is,” he explained. As the authors themselves conceded, visits for nutritional issues are especially difficult to sort out. “If you're seeing a patient because of a nutritional issue, it might be because he has a nutritional issue or it might be because you're concerned that he might develop one. So you wouldn't want to say that the responsible surgeon who is just following up on his patient within the first 180 days and monitoring a nutritional issue necessarily [indicates] a complication,” said Dr. Hutter, who is director of the Center for Clinical Effectiveness in Surgery at Massachusetts General Hospital, Boston.

According to the study, 18.2% of the patients with postoperative complications were readmitted, visited the emergency department, or were treated as outpatients. The most costly aspect of bariatric surgery was readmission: Total 6-month risk-adjusted inpatient and outpatient health care payments were 140% higher for those with 180-day readmissions with complications. Total 6-month risk-adjusted health care payments were $65,031 for those with 180-day readmission, compared with $27,125 for those without readmission.

For their data source, the authors used the MarketScan Commercial Claims and Encounter Database created by the Medstat Group for 2001 and 2002. The database covered approximately 5.6 million enrollees under the age of 65 in employer-sponsored benefit plans for 45 large employers.

Patients with more than one comorbidity were more likely to have a complication diagnosed during readmission, an outpatient hospital visit, or an office visit. Although there was no difference between men and women, older individuals had a 26% higher risk-adjusted complication rate than did those aged 18–39 years.

The authors cited the following limitations of their study: the inability to track deaths outside the hospital, which accounted for the low death rate of 0.2%; the lack of information regarding patients' body mass indexes; and, in their risk-adjusted regressions, the inability to control for surgeon and hospital bariatric volume. “Hospitals with more experience may have fewer complications,” they said. “However, in a subset of 625 surgeries in which we had bariatric volume, we found no link between volume and the risk of complication after adjusting for age, sex, and number of comorbidities.

“As patients, payers, and … physicians increasingly consider gastric bypass surgery for treatment of morbid obesity, this study provides representative information regarding complications and clinical risks after surgery for the privately insured, relatively young population. The risk of a complication and readmission was significant for both clinical outcomes and costs, which provides incentive for intervention and improvement,” the investigators concluded.

While applauding the authors for shedding more light on this topic, Dr. Hutter said future research “should compare apples to apples. In this study, we don't know what to compare the numbers to.”

He added that in addition to trips to the emergency department and hospital visits, “perhaps we also should look at real outcomes for patients, such as weight reduction and loss of comorbidities including diabetes, hypertension, sleep apnea, and hypercholesterolemia, and compare them with a group of untreated obese patients, and for a period of time longer than 180 days.”

A nationwide population-based study suggests that the rate of complications 6 months after bariatric surgery is higher than previous research suggested, and that resultant hospital readmissions increase health care costs.

“A clear way to reduce the costs and improve outcomes of bariatric surgery is to address the high rate of postoperative complications,” said William E. Encinosa, Ph.D., and his colleagues at the Agency for Healthcare Research and Quality in Rockville, Md.

The study of insurance claims data across 49 states in 2001 and 2002 found that nearly 40% of bariatric surgery patients experienced a complication within 180 days of being discharged, while 22% of patients had a complication prior to discharge (Medical Care 2006;44:706–12). That represents an 81% increase in complications over the 6 months after surgery, compared with the 10%–20% range found in the literature, the authors said.

The five most common complications were dumping syndrome (19.5%), complications of the anastomosis (12.3%), abdominal hernia (7%), infection (5.7%), and pneumonia (4.1%).

However, the study is weakened by its reliance on claims data, Dr. Matthew M. Hutter said in an interview. “Reliance on claim forms data makes it difficult to determine what a complication is,” he explained. As the authors themselves conceded, visits for nutritional issues are especially difficult to sort out. “If you're seeing a patient because of a nutritional issue, it might be because he has a nutritional issue or it might be because you're concerned that he might develop one. So you wouldn't want to say that the responsible surgeon who is just following up on his patient within the first 180 days and monitoring a nutritional issue necessarily [indicates] a complication,” said Dr. Hutter, who is director of the Center for Clinical Effectiveness in Surgery at Massachusetts General Hospital, Boston.

According to the study, 18.2% of the patients with postoperative complications were readmitted, visited the emergency department, or were treated as outpatients. The most costly aspect of bariatric surgery was readmission: Total 6-month risk-adjusted inpatient and outpatient health care payments were 140% higher for those with 180-day readmissions with complications. Total 6-month risk-adjusted health care payments were $65,031 for those with 180-day readmission, compared with $27,125 for those without readmission.

For their data source, the authors used the MarketScan Commercial Claims and Encounter Database created by the Medstat Group for 2001 and 2002. The database covered approximately 5.6 million enrollees under the age of 65 in employer-sponsored benefit plans for 45 large employers.

Patients with more than one comorbidity were more likely to have a complication diagnosed during readmission, an outpatient hospital visit, or an office visit. Although there was no difference between men and women, older individuals had a 26% higher risk-adjusted complication rate than did those aged 18–39 years.

The authors cited the following limitations of their study: the inability to track deaths outside the hospital, which accounted for the low death rate of 0.2%; the lack of information regarding patients' body mass indexes; and, in their risk-adjusted regressions, the inability to control for surgeon and hospital bariatric volume. “Hospitals with more experience may have fewer complications,” they said. “However, in a subset of 625 surgeries in which we had bariatric volume, we found no link between volume and the risk of complication after adjusting for age, sex, and number of comorbidities.

“As patients, payers, and … physicians increasingly consider gastric bypass surgery for treatment of morbid obesity, this study provides representative information regarding complications and clinical risks after surgery for the privately insured, relatively young population. The risk of a complication and readmission was significant for both clinical outcomes and costs, which provides incentive for intervention and improvement,” the investigators concluded.

While applauding the authors for shedding more light on this topic, Dr. Hutter said future research “should compare apples to apples. In this study, we don't know what to compare the numbers to.”

He added that in addition to trips to the emergency department and hospital visits, “perhaps we also should look at real outcomes for patients, such as weight reduction and loss of comorbidities including diabetes, hypertension, sleep apnea, and hypercholesterolemia, and compare them with a group of untreated obese patients, and for a period of time longer than 180 days.”

A nationwide population-based study suggests that the rate of complications 6 months after bariatric surgery is higher than previous research suggested, and that resultant hospital readmissions increase health care costs.

“A clear way to reduce the costs and improve outcomes of bariatric surgery is to address the high rate of postoperative complications,” said William E. Encinosa, Ph.D., and his colleagues at the Agency for Healthcare Research and Quality in Rockville, Md.

The study of insurance claims data across 49 states in 2001 and 2002 found that nearly 40% of bariatric surgery patients experienced a complication within 180 days of being discharged, while 22% of patients had a complication prior to discharge (Medical Care 2006;44:706–12). That represents an 81% increase in complications over the 6 months after surgery, compared with the 10%–20% range found in the literature, the authors said.

The five most common complications were dumping syndrome (19.5%), complications of the anastomosis (12.3%), abdominal hernia (7%), infection (5.7%), and pneumonia (4.1%).

However, the study is weakened by its reliance on claims data, Dr. Matthew M. Hutter said in an interview. “Reliance on claim forms data makes it difficult to determine what a complication is,” he explained. As the authors themselves conceded, visits for nutritional issues are especially difficult to sort out. “If you're seeing a patient because of a nutritional issue, it might be because he has a nutritional issue or it might be because you're concerned that he might develop one. So you wouldn't want to say that the responsible surgeon who is just following up on his patient within the first 180 days and monitoring a nutritional issue necessarily [indicates] a complication,” said Dr. Hutter, who is director of the Center for Clinical Effectiveness in Surgery at Massachusetts General Hospital, Boston.

According to the study, 18.2% of the patients with postoperative complications were readmitted, visited the emergency department, or were treated as outpatients. The most costly aspect of bariatric surgery was readmission: Total 6-month risk-adjusted inpatient and outpatient health care payments were 140% higher for those with 180-day readmissions with complications. Total 6-month risk-adjusted health care payments were $65,031 for those with 180-day readmission, compared with $27,125 for those without readmission.

For their data source, the authors used the MarketScan Commercial Claims and Encounter Database created by the Medstat Group for 2001 and 2002. The database covered approximately 5.6 million enrollees under the age of 65 in employer-sponsored benefit plans for 45 large employers.

Patients with more than one comorbidity were more likely to have a complication diagnosed during readmission, an outpatient hospital visit, or an office visit. Although there was no difference between men and women, older individuals had a 26% higher risk-adjusted complication rate than did those aged 18–39 years.

The authors cited the following limitations of their study: the inability to track deaths outside the hospital, which accounted for the low death rate of 0.2%; the lack of information regarding patients' body mass indexes; and, in their risk-adjusted regressions, the inability to control for surgeon and hospital bariatric volume. “Hospitals with more experience may have fewer complications,” they said. “However, in a subset of 625 surgeries in which we had bariatric volume, we found no link between volume and the risk of complication after adjusting for age, sex, and number of comorbidities.

“As patients, payers, and … physicians increasingly consider gastric bypass surgery for treatment of morbid obesity, this study provides representative information regarding complications and clinical risks after surgery for the privately insured, relatively young population. The risk of a complication and readmission was significant for both clinical outcomes and costs, which provides incentive for intervention and improvement,” the investigators concluded.

While applauding the authors for shedding more light on this topic, Dr. Hutter said future research “should compare apples to apples. In this study, we don't know what to compare the numbers to.”

He added that in addition to trips to the emergency department and hospital visits, “perhaps we also should look at real outcomes for patients, such as weight reduction and loss of comorbidities including diabetes, hypertension, sleep apnea, and hypercholesterolemia, and compare them with a group of untreated obese patients, and for a period of time longer than 180 days.”

Canadian researchers have taken an important step in the long-running process of identifying genetic causes of psoriatic arthritis.

The analysis, which targeted polymorphisms in the tumor necrosis factor-α (TNF-α) gene in two psoriatic arthritis populations, suggests that the −238(A) variant is a significant risk factor for this disease (Ann. Rheum. Dis. 2006;65:919–23).

The study involved 237 psoriatic arthritis patients and 103 controls from Newfoundland and 203 patients and 101 controls from Toronto. The mean age of patients in both groups was 50 years. With respect to the subtype of psoriatic arthritis in the two populations, 61% had the polyarticular pattern, 27% had the oligoarticular pattern, 5% had isolated spondyloarthropathy, and 7% had assorted other patterns, explained Dr. Proton Rahman and colleagues at St. Clare's Mercy Hospital in St. Johns, Newfoundland.

“Before our study, a significant association for TNF-α and psoriatic arthritis was noted only in German populations. We examined five common variants with the TNF-α promoter gene, including −238 and −308. We noted a significant association between −238 variant and psoriatic arthritis,” explained the investigators, who took the additional step of conducting a pooled analysis of nine cohorts from eight studies (including their own two Canadian cohorts). Again, the −238(A) gene polymorphism was a significant risk factor, though the six outside studies each used fewer than 150 probands and may have been underpowered.

“We acknowledge that population stratification was not entirely avoided as family-based controls were not used in these studies,” the authors said, adding that publication bias may exist in the metaanalysis, because small, negative association studies often are not published. “As demonstrated in our study, because metaanalysis of association studies in complex diseases [is] helpful in estimating population-wide genetic effects, further efforts must be made to track all association data for a given polymorphism,” they wrote.

The targeting of the TNF-α gene is supported by studies noting significantly higher serum, synovial fluid, and synovial membrane levels of TNF-α in patients with psoriatic arthritis, compared with either patients with osteoarthritis or healthy controls, the investigators point out. “The importance of TNF-α in psoriatic arthritis is further strengthened by the marked clinical response of TNF-α blockade.”

However, genetic studies have produced conflicting results, with inconsistencies that may reflect insufficient sample sizes, differences in populations, the presence of linkage disequilibrium, or multiple testing, the authors said.

Canadian researchers have taken an important step in the long-running process of identifying genetic causes of psoriatic arthritis.

The analysis, which targeted polymorphisms in the tumor necrosis factor-α (TNF-α) gene in two psoriatic arthritis populations, suggests that the −238(A) variant is a significant risk factor for this disease (Ann. Rheum. Dis. 2006;65:919–23).

The study involved 237 psoriatic arthritis patients and 103 controls from Newfoundland and 203 patients and 101 controls from Toronto. The mean age of patients in both groups was 50 years. With respect to the subtype of psoriatic arthritis in the two populations, 61% had the polyarticular pattern, 27% had the oligoarticular pattern, 5% had isolated spondyloarthropathy, and 7% had assorted other patterns, explained Dr. Proton Rahman and colleagues at St. Clare's Mercy Hospital in St. Johns, Newfoundland.

“Before our study, a significant association for TNF-α and psoriatic arthritis was noted only in German populations. We examined five common variants with the TNF-α promoter gene, including −238 and −308. We noted a significant association between −238 variant and psoriatic arthritis,” explained the investigators, who took the additional step of conducting a pooled analysis of nine cohorts from eight studies (including their own two Canadian cohorts). Again, the −238(A) gene polymorphism was a significant risk factor, though the six outside studies each used fewer than 150 probands and may have been underpowered.

“We acknowledge that population stratification was not entirely avoided as family-based controls were not used in these studies,” the authors said, adding that publication bias may exist in the metaanalysis, because small, negative association studies often are not published. “As demonstrated in our study, because metaanalysis of association studies in complex diseases [is] helpful in estimating population-wide genetic effects, further efforts must be made to track all association data for a given polymorphism,” they wrote.

The targeting of the TNF-α gene is supported by studies noting significantly higher serum, synovial fluid, and synovial membrane levels of TNF-α in patients with psoriatic arthritis, compared with either patients with osteoarthritis or healthy controls, the investigators point out. “The importance of TNF-α in psoriatic arthritis is further strengthened by the marked clinical response of TNF-α blockade.”

However, genetic studies have produced conflicting results, with inconsistencies that may reflect insufficient sample sizes, differences in populations, the presence of linkage disequilibrium, or multiple testing, the authors said.

Canadian researchers have taken an important step in the long-running process of identifying genetic causes of psoriatic arthritis.

The analysis, which targeted polymorphisms in the tumor necrosis factor-α (TNF-α) gene in two psoriatic arthritis populations, suggests that the −238(A) variant is a significant risk factor for this disease (Ann. Rheum. Dis. 2006;65:919–23).

The study involved 237 psoriatic arthritis patients and 103 controls from Newfoundland and 203 patients and 101 controls from Toronto. The mean age of patients in both groups was 50 years. With respect to the subtype of psoriatic arthritis in the two populations, 61% had the polyarticular pattern, 27% had the oligoarticular pattern, 5% had isolated spondyloarthropathy, and 7% had assorted other patterns, explained Dr. Proton Rahman and colleagues at St. Clare's Mercy Hospital in St. Johns, Newfoundland.

“Before our study, a significant association for TNF-α and psoriatic arthritis was noted only in German populations. We examined five common variants with the TNF-α promoter gene, including −238 and −308. We noted a significant association between −238 variant and psoriatic arthritis,” explained the investigators, who took the additional step of conducting a pooled analysis of nine cohorts from eight studies (including their own two Canadian cohorts). Again, the −238(A) gene polymorphism was a significant risk factor, though the six outside studies each used fewer than 150 probands and may have been underpowered.

“We acknowledge that population stratification was not entirely avoided as family-based controls were not used in these studies,” the authors said, adding that publication bias may exist in the metaanalysis, because small, negative association studies often are not published. “As demonstrated in our study, because metaanalysis of association studies in complex diseases [is] helpful in estimating population-wide genetic effects, further efforts must be made to track all association data for a given polymorphism,” they wrote.

The targeting of the TNF-α gene is supported by studies noting significantly higher serum, synovial fluid, and synovial membrane levels of TNF-α in patients with psoriatic arthritis, compared with either patients with osteoarthritis or healthy controls, the investigators point out. “The importance of TNF-α in psoriatic arthritis is further strengthened by the marked clinical response of TNF-α blockade.”

However, genetic studies have produced conflicting results, with inconsistencies that may reflect insufficient sample sizes, differences in populations, the presence of linkage disequilibrium, or multiple testing, the authors said.

SCOTTSDALE, ARIZ. — Pressure ulcers should be treated early using validated protocols of care to keep them from becoming infected or advancing to full-thickness wounds, Dr. Laura Bolton said at the annual meeting of the Wound Healing Society.

“A full-thickness pressure ulcer takes twice as long to heal as a partial-thickness ulcer, and in our real-world pressure ulcer outcome study, baseline infection predicted delayed healing,” said Dr. Bolton of the bioengineering section of the department of surgery at the Robert Wood Johnson Medical School in New Brunswick, N.J.

Pressure ulcer healing is further delayed by the use of gauze dressings. “When hydrocolloid and fibrous dressings, such as a Hydrofiber, were used, the wounds healed three times faster than when gauze only was applied. We were surprised to see that nearly 9% of pressure ulcers entered the study infected. Controlling for wound depth and pain, baseline infection predicted delayed healing,” she said.

From March 2001 to December 2002, Dr. Bolton and her colleagues collected data on 297 patients with 821 stage II, III, or IV pressure ulcers treated at five home care agencies via telemedicine, a long-term care facility at point of care, and a long-term acute care hospital at point of care.

The purpose was to conduct research without the rigor or exclusion criteria of a prospective, randomized controlled study. Although clinical studies produce much-needed evidence of comparative product safety and efficacy, she said, “the scientific rigor that makes them valuable support for clinical decision making also isolates them from the realm of normal practice.”

All patients were managed by wound specialists using standardizing documentation and care and an adapted Pressure Sore Status Tool with pain assessments.

In this cohort with pressure ulcers, 74% of the patients were older than 70 years of age and 60% were female. Full-thickness wounds, which composed 60% of all pressure ulcers, had a median area of 4 cm, while partial-thickness (28%) had a median area of 2.4 cm, and the 11% of ulcers with unknown depth had a median area of 6 cm.

The mean healing time of smaller (below median area) partial-thickness wounds was 24 days, compared with 58 days for smaller full-thickness ulcers and those of unknown depth. Large partial-thickness ulcers took an average of 50 days to heal, compared with 121 days for unknown-depth ulcers and 167 days for full-thickness pressure ulcers. “Within the partial-thickness and unknown-depth subsets, smaller area drove faster wound healing, and for all depths of ulcers, a decrease of 20% in area during the first 2 weeks of care predicted faster healing,” Dr. Bolton said.

At least one sign of infection was found in more than 20% of pressure ulcers. Partial-thickness and unknown-depth pressure ulcers were less than half as likely to become infected during the study, compared with full-thickness pressure ulcers. Controlling for patient age and baseline wound depth, pressure ulcers with at least one infection were almost twice as likely to have some pain.

The study was funded by ConvaTec, a Bristol-Myers Squibb company.

'We were surprised to see that nearly 9% of pressure ulcers entered the study infected.' DR. BOLTON

ELSEVIER GLOBAL MEDICAL NEWS

SCOTTSDALE, ARIZ. — Pressure ulcers should be treated early using validated protocols of care to keep them from becoming infected or advancing to full-thickness wounds, Dr. Laura Bolton said at the annual meeting of the Wound Healing Society.

“A full-thickness pressure ulcer takes twice as long to heal as a partial-thickness ulcer, and in our real-world pressure ulcer outcome study, baseline infection predicted delayed healing,” said Dr. Bolton of the bioengineering section of the department of surgery at the Robert Wood Johnson Medical School in New Brunswick, N.J.

Pressure ulcer healing is further delayed by the use of gauze dressings. “When hydrocolloid and fibrous dressings, such as a Hydrofiber, were used, the wounds healed three times faster than when gauze only was applied. We were surprised to see that nearly 9% of pressure ulcers entered the study infected. Controlling for wound depth and pain, baseline infection predicted delayed healing,” she said.

From March 2001 to December 2002, Dr. Bolton and her colleagues collected data on 297 patients with 821 stage II, III, or IV pressure ulcers treated at five home care agencies via telemedicine, a long-term care facility at point of care, and a long-term acute care hospital at point of care.

The purpose was to conduct research without the rigor or exclusion criteria of a prospective, randomized controlled study. Although clinical studies produce much-needed evidence of comparative product safety and efficacy, she said, “the scientific rigor that makes them valuable support for clinical decision making also isolates them from the realm of normal practice.”

All patients were managed by wound specialists using standardizing documentation and care and an adapted Pressure Sore Status Tool with pain assessments.

In this cohort with pressure ulcers, 74% of the patients were older than 70 years of age and 60% were female. Full-thickness wounds, which composed 60% of all pressure ulcers, had a median area of 4 cm, while partial-thickness (28%) had a median area of 2.4 cm, and the 11% of ulcers with unknown depth had a median area of 6 cm.

The mean healing time of smaller (below median area) partial-thickness wounds was 24 days, compared with 58 days for smaller full-thickness ulcers and those of unknown depth. Large partial-thickness ulcers took an average of 50 days to heal, compared with 121 days for unknown-depth ulcers and 167 days for full-thickness pressure ulcers. “Within the partial-thickness and unknown-depth subsets, smaller area drove faster wound healing, and for all depths of ulcers, a decrease of 20% in area during the first 2 weeks of care predicted faster healing,” Dr. Bolton said.

At least one sign of infection was found in more than 20% of pressure ulcers. Partial-thickness and unknown-depth pressure ulcers were less than half as likely to become infected during the study, compared with full-thickness pressure ulcers. Controlling for patient age and baseline wound depth, pressure ulcers with at least one infection were almost twice as likely to have some pain.

The study was funded by ConvaTec, a Bristol-Myers Squibb company.

'We were surprised to see that nearly 9% of pressure ulcers entered the study infected.' DR. BOLTON

ELSEVIER GLOBAL MEDICAL NEWS

SCOTTSDALE, ARIZ. — Pressure ulcers should be treated early using validated protocols of care to keep them from becoming infected or advancing to full-thickness wounds, Dr. Laura Bolton said at the annual meeting of the Wound Healing Society.

“A full-thickness pressure ulcer takes twice as long to heal as a partial-thickness ulcer, and in our real-world pressure ulcer outcome study, baseline infection predicted delayed healing,” said Dr. Bolton of the bioengineering section of the department of surgery at the Robert Wood Johnson Medical School in New Brunswick, N.J.

Pressure ulcer healing is further delayed by the use of gauze dressings. “When hydrocolloid and fibrous dressings, such as a Hydrofiber, were used, the wounds healed three times faster than when gauze only was applied. We were surprised to see that nearly 9% of pressure ulcers entered the study infected. Controlling for wound depth and pain, baseline infection predicted delayed healing,” she said.

From March 2001 to December 2002, Dr. Bolton and her colleagues collected data on 297 patients with 821 stage II, III, or IV pressure ulcers treated at five home care agencies via telemedicine, a long-term care facility at point of care, and a long-term acute care hospital at point of care.

The purpose was to conduct research without the rigor or exclusion criteria of a prospective, randomized controlled study. Although clinical studies produce much-needed evidence of comparative product safety and efficacy, she said, “the scientific rigor that makes them valuable support for clinical decision making also isolates them from the realm of normal practice.”

All patients were managed by wound specialists using standardizing documentation and care and an adapted Pressure Sore Status Tool with pain assessments.

In this cohort with pressure ulcers, 74% of the patients were older than 70 years of age and 60% were female. Full-thickness wounds, which composed 60% of all pressure ulcers, had a median area of 4 cm, while partial-thickness (28%) had a median area of 2.4 cm, and the 11% of ulcers with unknown depth had a median area of 6 cm.

The mean healing time of smaller (below median area) partial-thickness wounds was 24 days, compared with 58 days for smaller full-thickness ulcers and those of unknown depth. Large partial-thickness ulcers took an average of 50 days to heal, compared with 121 days for unknown-depth ulcers and 167 days for full-thickness pressure ulcers. “Within the partial-thickness and unknown-depth subsets, smaller area drove faster wound healing, and for all depths of ulcers, a decrease of 20% in area during the first 2 weeks of care predicted faster healing,” Dr. Bolton said.

At least one sign of infection was found in more than 20% of pressure ulcers. Partial-thickness and unknown-depth pressure ulcers were less than half as likely to become infected during the study, compared with full-thickness pressure ulcers. Controlling for patient age and baseline wound depth, pressure ulcers with at least one infection were almost twice as likely to have some pain.

The study was funded by ConvaTec, a Bristol-Myers Squibb company.

'We were surprised to see that nearly 9% of pressure ulcers entered the study infected.' DR. BOLTON

ELSEVIER GLOBAL MEDICAL NEWS

Age, education and cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in Lancet Neurology (Aug. 3, 2006; Epub ahead of print; doi:10.1016/S1474-4422(06)70537-3). The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” the investigators reported.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later. Of these patients, 4% were diagnosed with dementia.

Based on the prediction model, future dementia was associated with an age of 47 years or older, less than 10 years of education, systolic blood pressure greater than 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30 kg/m

Gender, smoking, and physical activity were not significantly associated with dementia. In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive of risk and cholesterol less so, the investigators reported.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, HDL and LDL levels, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators noted. Further research is needed to validate their dementia risk score in other populations.

Age, education and cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in Lancet Neurology (Aug. 3, 2006; Epub ahead of print; doi:10.1016/S1474-4422(06)70537-3). The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” the investigators reported.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later. Of these patients, 4% were diagnosed with dementia.

Based on the prediction model, future dementia was associated with an age of 47 years or older, less than 10 years of education, systolic blood pressure greater than 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30 kg/m

Gender, smoking, and physical activity were not significantly associated with dementia. In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive of risk and cholesterol less so, the investigators reported.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, HDL and LDL levels, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators noted. Further research is needed to validate their dementia risk score in other populations.

Age, education and cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in Lancet Neurology (Aug. 3, 2006; Epub ahead of print; doi:10.1016/S1474-4422(06)70537-3). The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” the investigators reported.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later. Of these patients, 4% were diagnosed with dementia.

Based on the prediction model, future dementia was associated with an age of 47 years or older, less than 10 years of education, systolic blood pressure greater than 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30 kg/m

Gender, smoking, and physical activity were not significantly associated with dementia. In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive of risk and cholesterol less so, the investigators reported.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, HDL and LDL levels, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators noted. Further research is needed to validate their dementia risk score in other populations.

CHICAGO — Family history plays a larger role in Barrett's esophagus and associated cancers than was previously recognized, according to Dr. Amitabh Chak.

“There's clearly an inheritance pattern that suggests an autosomal dominant disease,” said Dr. Chak at the annual midwestern clinical research meeting.

Efforts to track down a genetic basis for Barrett's esophagus (BE) and related adenocarcinomas began with a cross-sectional pilot study by Dr. Chak, a gastroenterologist at Case Western Reserve University, Cleveland, and his colleagues. The researchers compared 56 patients with BE or adenocarcinoma of the esophagus or gastroesophageal junction with 106 control patients who had gastroesophageal reflux.

“The striking finding was that the Barrett's and esophageal cancer cases reported a positive family history for these diseases significantly more often than did the reflux controls,” Dr. Chak said at the meeting of the Central Society for Clinical Research and the Midwestern Section of the American Federation for Medical Research.

“That pilot study led us to formulate the more focused hypothesis that BE and associated cancers are complex genetic diseases with a combined underlying genetic and environmental cause, and I think there's an inherited susceptibility to develop intestinal metaplasia, but that susceptibility may be present in only a subset of these patients who have this disease,” he said.

To test their hypothesis, the investigators went on a “gene hunt,” beginning with the endoscopic screening of relatives with BE or esophageal cancer.

The breakthrough came with the identification of a large family with 13 affected members. The findings showed an inheritance pattern that suggested an autosomal dominant disease, Dr. Chak said.

With the help of other investigators in the Familial Barrett's Esophagus Consortium, the Case Western team began to accumulate prospective data on the affected families and published its first report on their phenotypes and demographics in 2004. The researchers found that endoscopy could identify esophageal cancer and Barrett's epithelium in a substantial proportion of first-degree relatives of affected members of 69 of the families. In addition, a familial susceptibility to develop Barrett's epithelium appeared to be present in a subset of patients who had BE and esophageal cancer (Am. J. Gastroenterol. 2004;99:2107–14).

The database, which has now grown to include 140 families, shows that 7.3% of 413 probands have a confirmed affected (with BE or esophageal cancer) first-degree or second-degree relative.

“We compared the risk factors for BE in familial and nonfamilial BE and esophageal cancer, and the main difference was that familial patients with cancer have a lower body mass index at diagnosis and at 1, 5, and 10 years prior to diagnosis,” he said.

Familial Barrett's esophagus probands with cancer may be less obese and have shorter durations of obesity than those with apparently “sporadic” cancer, Dr. Chak added.

The researchers currently are conducting linkage analysis to identify putative susceptibility genes and confirm their hypothesis.

Meanwhile, Dr. Chak's recommendation is that all susceptible patients be screened endoscopically, which can be done relatively quickly and without sedation using an ultrathin endoscope.

Screening should include individuals with reflux who have two or more family members with Barrett's esophagus or esophageal cancer, one of whom is a first-degree relative (parent, sibling, or child), Dr. Chak said in an interview.

An unusual incidence of disease in second-degree relatives should also raise suspicion, he added.

Individuals with reflux who have two or more family members affected, one a first-degree relative, should be screened. DR. CHAK

CHICAGO — Family history plays a larger role in Barrett's esophagus and associated cancers than was previously recognized, according to Dr. Amitabh Chak.

“There's clearly an inheritance pattern that suggests an autosomal dominant disease,” said Dr. Chak at the annual midwestern clinical research meeting.

Efforts to track down a genetic basis for Barrett's esophagus (BE) and related adenocarcinomas began with a cross-sectional pilot study by Dr. Chak, a gastroenterologist at Case Western Reserve University, Cleveland, and his colleagues. The researchers compared 56 patients with BE or adenocarcinoma of the esophagus or gastroesophageal junction with 106 control patients who had gastroesophageal reflux.

“The striking finding was that the Barrett's and esophageal cancer cases reported a positive family history for these diseases significantly more often than did the reflux controls,” Dr. Chak said at the meeting of the Central Society for Clinical Research and the Midwestern Section of the American Federation for Medical Research.

“That pilot study led us to formulate the more focused hypothesis that BE and associated cancers are complex genetic diseases with a combined underlying genetic and environmental cause, and I think there's an inherited susceptibility to develop intestinal metaplasia, but that susceptibility may be present in only a subset of these patients who have this disease,” he said.

To test their hypothesis, the investigators went on a “gene hunt,” beginning with the endoscopic screening of relatives with BE or esophageal cancer.

The breakthrough came with the identification of a large family with 13 affected members. The findings showed an inheritance pattern that suggested an autosomal dominant disease, Dr. Chak said.

With the help of other investigators in the Familial Barrett's Esophagus Consortium, the Case Western team began to accumulate prospective data on the affected families and published its first report on their phenotypes and demographics in 2004. The researchers found that endoscopy could identify esophageal cancer and Barrett's epithelium in a substantial proportion of first-degree relatives of affected members of 69 of the families. In addition, a familial susceptibility to develop Barrett's epithelium appeared to be present in a subset of patients who had BE and esophageal cancer (Am. J. Gastroenterol. 2004;99:2107–14).

The database, which has now grown to include 140 families, shows that 7.3% of 413 probands have a confirmed affected (with BE or esophageal cancer) first-degree or second-degree relative.

“We compared the risk factors for BE in familial and nonfamilial BE and esophageal cancer, and the main difference was that familial patients with cancer have a lower body mass index at diagnosis and at 1, 5, and 10 years prior to diagnosis,” he said.

Familial Barrett's esophagus probands with cancer may be less obese and have shorter durations of obesity than those with apparently “sporadic” cancer, Dr. Chak added.

The researchers currently are conducting linkage analysis to identify putative susceptibility genes and confirm their hypothesis.

Meanwhile, Dr. Chak's recommendation is that all susceptible patients be screened endoscopically, which can be done relatively quickly and without sedation using an ultrathin endoscope.

Screening should include individuals with reflux who have two or more family members with Barrett's esophagus or esophageal cancer, one of whom is a first-degree relative (parent, sibling, or child), Dr. Chak said in an interview.

An unusual incidence of disease in second-degree relatives should also raise suspicion, he added.

Individuals with reflux who have two or more family members affected, one a first-degree relative, should be screened. DR. CHAK

CHICAGO — Family history plays a larger role in Barrett's esophagus and associated cancers than was previously recognized, according to Dr. Amitabh Chak.

“There's clearly an inheritance pattern that suggests an autosomal dominant disease,” said Dr. Chak at the annual midwestern clinical research meeting.

Efforts to track down a genetic basis for Barrett's esophagus (BE) and related adenocarcinomas began with a cross-sectional pilot study by Dr. Chak, a gastroenterologist at Case Western Reserve University, Cleveland, and his colleagues. The researchers compared 56 patients with BE or adenocarcinoma of the esophagus or gastroesophageal junction with 106 control patients who had gastroesophageal reflux.

“The striking finding was that the Barrett's and esophageal cancer cases reported a positive family history for these diseases significantly more often than did the reflux controls,” Dr. Chak said at the meeting of the Central Society for Clinical Research and the Midwestern Section of the American Federation for Medical Research.

“That pilot study led us to formulate the more focused hypothesis that BE and associated cancers are complex genetic diseases with a combined underlying genetic and environmental cause, and I think there's an inherited susceptibility to develop intestinal metaplasia, but that susceptibility may be present in only a subset of these patients who have this disease,” he said.

To test their hypothesis, the investigators went on a “gene hunt,” beginning with the endoscopic screening of relatives with BE or esophageal cancer.

The breakthrough came with the identification of a large family with 13 affected members. The findings showed an inheritance pattern that suggested an autosomal dominant disease, Dr. Chak said.

With the help of other investigators in the Familial Barrett's Esophagus Consortium, the Case Western team began to accumulate prospective data on the affected families and published its first report on their phenotypes and demographics in 2004. The researchers found that endoscopy could identify esophageal cancer and Barrett's epithelium in a substantial proportion of first-degree relatives of affected members of 69 of the families. In addition, a familial susceptibility to develop Barrett's epithelium appeared to be present in a subset of patients who had BE and esophageal cancer (Am. J. Gastroenterol. 2004;99:2107–14).

The database, which has now grown to include 140 families, shows that 7.3% of 413 probands have a confirmed affected (with BE or esophageal cancer) first-degree or second-degree relative.

“We compared the risk factors for BE in familial and nonfamilial BE and esophageal cancer, and the main difference was that familial patients with cancer have a lower body mass index at diagnosis and at 1, 5, and 10 years prior to diagnosis,” he said.

Familial Barrett's esophagus probands with cancer may be less obese and have shorter durations of obesity than those with apparently “sporadic” cancer, Dr. Chak added.

The researchers currently are conducting linkage analysis to identify putative susceptibility genes and confirm their hypothesis.

Meanwhile, Dr. Chak's recommendation is that all susceptible patients be screened endoscopically, which can be done relatively quickly and without sedation using an ultrathin endoscope.

Screening should include individuals with reflux who have two or more family members with Barrett's esophagus or esophageal cancer, one of whom is a first-degree relative (parent, sibling, or child), Dr. Chak said in an interview.

An unusual incidence of disease in second-degree relatives should also raise suspicion, he added.

Individuals with reflux who have two or more family members affected, one a first-degree relative, should be screened. DR. CHAK

Advancing age, limited education, high cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in the Lancet Neurology (Epub ahead of print: doi 10.1016/S1474–4422(06)70537–3).

The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” they said.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later; 4% were diagnosed with dementia.

Future dementia was associated with age 47 or older, less than 10 years of education, systolic blood pressure over 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30). In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive and cholesterol less so.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, concentrations of high- and low-density lipoproteins, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators explained, adding that further research is needed to validate the dementia risk score.

Advancing age, limited education, high cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in the Lancet Neurology (Epub ahead of print: doi 10.1016/S1474–4422(06)70537–3).

The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” they said.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later; 4% were diagnosed with dementia.

Future dementia was associated with age 47 or older, less than 10 years of education, systolic blood pressure over 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30). In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive and cholesterol less so.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, concentrations of high- and low-density lipoproteins, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators explained, adding that further research is needed to validate the dementia risk score.

Advancing age, limited education, high cholesterol levels, high blood pressure, and obesity at midlife are significantly associated with the later development of dementia, according to findings from a 20-year follow-up study.

A new, simple dementia-risk prediction tool may allow for the earlier detection of the disease based on these midlife factors, Miia Kivipelto of the Karolinska Institute in Stockholm and colleagues reported in the Lancet Neurology (Epub ahead of print: doi 10.1016/S1474–4422(06)70537–3).

The detection technique highlights the role of vascular factors in the development of dementia “and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions,” they said.

Data were derived from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, in which 1,409 patients were studied in midlife and reexamined 20 years later; 4% were diagnosed with dementia.

Future dementia was associated with age 47 or older, less than 10 years of education, systolic blood pressure over 140 mm Hg, high cholesterol levels greater than 6.5 mmol/L, and obesity (body mass index over 30). In a second model that factored in apolipoprotein ϵ4 status (carriers vs. noncarriers), age and education became more predictive and cholesterol less so.

Potential risk factors not examined in this study include a family history of dementia, serum triglyceride levels, concentrations of high- and low-density lipoproteins, waist-to-hip ratio, and diabetes (insulin resistance). “There is much evidence that diabetes is associated with an increased risk of dementia, and thus its inclusion in future risk scores is important,” the investigators explained, adding that further research is needed to validate the dementia risk score.

SCOTTSDALE, ARIZ. — Negative pressure wound therapy need not be restricted to adults, Dr. Bindi Naik-Mathuria said at the annual meeting of the Wound Healing Society.

"The results of our large retrospective review suggest that negative pressure wound therapy is effective in children of all ages and for a wide variety of wounds, and the therapy can be safely used in this population, with appropriate precautions," said Dr. Naik-Mathuria of the division of pediatric surgery, Baylor College of Medicine and Texas Children's Hospital, both in Houston.

In adults, negative pressure wound therapy (NPWT) removes excess wound fluid and exudate, increases wound vascularity, and promotes granulation tissue. Data on its use in children are limited.

This study, which prompted some debate during the presentation's question and answer period, evaluated a single institution's experience with a vacuum-assisted closure (VAC) system to manage a variety of wounds in children ranging in age from 7 days to 18 years.

Between 2003 and 2005, Dr. Naik-Mathuria and her colleagues identified 71 patients with 87 wounds. The gender ratio was evenly divided, and the average age was just short of 9 years. There were seven neonates in the VAC therapy group. "These numbers make this study one of the largest reported in pediatric patients to date and certainly the largest in infants and very young children," she said.

NPWT was used for various wound types, including pressure ulcers, dehisced surgical wounds, open sternal wounds, extremity wounds, wounds with fistula, and abdominal wall defects in neonates (gastroschisis, omphalocele, and abdominal compartment syndrome). "What's especially interesting about these cases is how negative pressure was used in creative ways to heal complex wounds [for] neonates and infants, and how it worked so well that additional surgery was, in many cases, avoided," said Dr. Naik-Mathuria, who cited examples:

▸ A 1-year-old with a large thickness wound following liver transplantation was too ill to undergo reoperation to close, requiring the application of a VAC dressing. The wound contracted significantly; granulation tissue filled the wound rapidly.

▸ A 1-year-old with necrotizing fasciitis was left with exposed vital structures of the lower leg after wide debridement. Instead of applying a complicated free flap, the surgeon used a local rotational muscle flap to cover the ankle joint and applied a VAC dressing. "Only 17 days later, granulation tissue filled the wound bed and provided a nice bed for skin grafting," she said.

"A total of 56 wounds were analyzed by type. The average decrease in wound volume was 80%, and 95% of wounds benefited from negative pressure therapy," she said, adding that for five wounds, follow-up data were not collected because the patients were transferred.

The four wounds that did not decrease in volume involved an immunocompromised patient, a chronically contaminated ischial wound, and two patients with persistent underlying infections. "This prompted us to examine how infection played a role in healing the other wounds, and we noted that while 26 wounds had documented infections that were being treated at wrap placement, 88% decreased in size without the progression of infection," she said.

On average, therapy duration was 25 days. Outpatient use of NPWT was documented in 19% and the therapy was generally well tolerated. "In fact, there was no discontinuation of use because of lack of tolerance or patient request, though it was discontinued in one neonate who developed a coagulopathy, causing concern about bleeding with continued treatment," Dr. Naik-Mathuria explained.

Minor complications included skin rash, maceration, and pain or minor bleeding with dressing changes.

Since "there are no guidelines for appropriate negative pressure therapy use in children, we tended to use lower pressures—down to 50 mm Hg—in younger children and in wounds with exposed organs. The normal pressure used in adults—125 mm Hg—is what we used in children aged 4 and older," said Dr. Naik-Mathuria, adding that, higher pressures can be used on denser tissues in the groin and extremities, while lower pressures should be used over the sternum and abdomen.

SCOTTSDALE, ARIZ. — Negative pressure wound therapy need not be restricted to adults, Dr. Bindi Naik-Mathuria said at the annual meeting of the Wound Healing Society.

"The results of our large retrospective review suggest that negative pressure wound therapy is effective in children of all ages and for a wide variety of wounds, and the therapy can be safely used in this population, with appropriate precautions," said Dr. Naik-Mathuria of the division of pediatric surgery, Baylor College of Medicine and Texas Children's Hospital, both in Houston.

In adults, negative pressure wound therapy (NPWT) removes excess wound fluid and exudate, increases wound vascularity, and promotes granulation tissue. Data on its use in children are limited.

This study, which prompted some debate during the presentation's question and answer period, evaluated a single institution's experience with a vacuum-assisted closure (VAC) system to manage a variety of wounds in children ranging in age from 7 days to 18 years.

Between 2003 and 2005, Dr. Naik-Mathuria and her colleagues identified 71 patients with 87 wounds. The gender ratio was evenly divided, and the average age was just short of 9 years. There were seven neonates in the VAC therapy group. "These numbers make this study one of the largest reported in pediatric patients to date and certainly the largest in infants and very young children," she said.

NPWT was used for various wound types, including pressure ulcers, dehisced surgical wounds, open sternal wounds, extremity wounds, wounds with fistula, and abdominal wall defects in neonates (gastroschisis, omphalocele, and abdominal compartment syndrome). "What's especially interesting about these cases is how negative pressure was used in creative ways to heal complex wounds [for] neonates and infants, and how it worked so well that additional surgery was, in many cases, avoided," said Dr. Naik-Mathuria, who cited examples:

▸ A 1-year-old with a large thickness wound following liver transplantation was too ill to undergo reoperation to close, requiring the application of a VAC dressing. The wound contracted significantly; granulation tissue filled the wound rapidly.

▸ A 1-year-old with necrotizing fasciitis was left with exposed vital structures of the lower leg after wide debridement. Instead of applying a complicated free flap, the surgeon used a local rotational muscle flap to cover the ankle joint and applied a VAC dressing. "Only 17 days later, granulation tissue filled the wound bed and provided a nice bed for skin grafting," she said.

"A total of 56 wounds were analyzed by type. The average decrease in wound volume was 80%, and 95% of wounds benefited from negative pressure therapy," she said, adding that for five wounds, follow-up data were not collected because the patients were transferred.

The four wounds that did not decrease in volume involved an immunocompromised patient, a chronically contaminated ischial wound, and two patients with persistent underlying infections. "This prompted us to examine how infection played a role in healing the other wounds, and we noted that while 26 wounds had documented infections that were being treated at wrap placement, 88% decreased in size without the progression of infection," she said.

On average, therapy duration was 25 days. Outpatient use of NPWT was documented in 19% and the therapy was generally well tolerated. "In fact, there was no discontinuation of use because of lack of tolerance or patient request, though it was discontinued in one neonate who developed a coagulopathy, causing concern about bleeding with continued treatment," Dr. Naik-Mathuria explained.

Minor complications included skin rash, maceration, and pain or minor bleeding with dressing changes.

Since "there are no guidelines for appropriate negative pressure therapy use in children, we tended to use lower pressures—down to 50 mm Hg—in younger children and in wounds with exposed organs. The normal pressure used in adults—125 mm Hg—is what we used in children aged 4 and older," said Dr. Naik-Mathuria, adding that, higher pressures can be used on denser tissues in the groin and extremities, while lower pressures should be used over the sternum and abdomen.

SCOTTSDALE, ARIZ. — Negative pressure wound therapy need not be restricted to adults, Dr. Bindi Naik-Mathuria said at the annual meeting of the Wound Healing Society.

"The results of our large retrospective review suggest that negative pressure wound therapy is effective in children of all ages and for a wide variety of wounds, and the therapy can be safely used in this population, with appropriate precautions," said Dr. Naik-Mathuria of the division of pediatric surgery, Baylor College of Medicine and Texas Children's Hospital, both in Houston.

In adults, negative pressure wound therapy (NPWT) removes excess wound fluid and exudate, increases wound vascularity, and promotes granulation tissue. Data on its use in children are limited.

This study, which prompted some debate during the presentation's question and answer period, evaluated a single institution's experience with a vacuum-assisted closure (VAC) system to manage a variety of wounds in children ranging in age from 7 days to 18 years.

Between 2003 and 2005, Dr. Naik-Mathuria and her colleagues identified 71 patients with 87 wounds. The gender ratio was evenly divided, and the average age was just short of 9 years. There were seven neonates in the VAC therapy group. "These numbers make this study one of the largest reported in pediatric patients to date and certainly the largest in infants and very young children," she said.

NPWT was used for various wound types, including pressure ulcers, dehisced surgical wounds, open sternal wounds, extremity wounds, wounds with fistula, and abdominal wall defects in neonates (gastroschisis, omphalocele, and abdominal compartment syndrome). "What's especially interesting about these cases is how negative pressure was used in creative ways to heal complex wounds [for] neonates and infants, and how it worked so well that additional surgery was, in many cases, avoided," said Dr. Naik-Mathuria, who cited examples:

▸ A 1-year-old with a large thickness wound following liver transplantation was too ill to undergo reoperation to close, requiring the application of a VAC dressing. The wound contracted significantly; granulation tissue filled the wound rapidly.

▸ A 1-year-old with necrotizing fasciitis was left with exposed vital structures of the lower leg after wide debridement. Instead of applying a complicated free flap, the surgeon used a local rotational muscle flap to cover the ankle joint and applied a VAC dressing. "Only 17 days later, granulation tissue filled the wound bed and provided a nice bed for skin grafting," she said.

"A total of 56 wounds were analyzed by type. The average decrease in wound volume was 80%, and 95% of wounds benefited from negative pressure therapy," she said, adding that for five wounds, follow-up data were not collected because the patients were transferred.

The four wounds that did not decrease in volume involved an immunocompromised patient, a chronically contaminated ischial wound, and two patients with persistent underlying infections. "This prompted us to examine how infection played a role in healing the other wounds, and we noted that while 26 wounds had documented infections that were being treated at wrap placement, 88% decreased in size without the progression of infection," she said.

On average, therapy duration was 25 days. Outpatient use of NPWT was documented in 19% and the therapy was generally well tolerated. "In fact, there was no discontinuation of use because of lack of tolerance or patient request, though it was discontinued in one neonate who developed a coagulopathy, causing concern about bleeding with continued treatment," Dr. Naik-Mathuria explained.

Minor complications included skin rash, maceration, and pain or minor bleeding with dressing changes.

Since "there are no guidelines for appropriate negative pressure therapy use in children, we tended to use lower pressures—down to 50 mm Hg—in younger children and in wounds with exposed organs. The normal pressure used in adults—125 mm Hg—is what we used in children aged 4 and older," said Dr. Naik-Mathuria, adding that, higher pressures can be used on denser tissues in the groin and extremities, while lower pressures should be used over the sternum and abdomen.

CHICAGO — Physical examination of the multidislocated knee is inadequate for determining the need for arteriography, according to a University of Michigan study.

“Routine arteriography is justified in multiligament injuries to the knee by the high incidence of popliteal artery injury, given the potentially devastating consequences of a delay in diagnosis and the relatively low morbidity of an arteriograph,” Dr. E. Barry McDonough told the annual meeting of the American Academy of Orthopaedic Surgeons.

Knee dislocation is rising in incidence due to increasing participation in sports, the popularity of all-terrain vehicles, and the boom in obesity, said Dr. McDonough, who is now with a group practice in Glen Ellyn, Ill.

Whereas anterior dislocations can be the result of a hyperextension injury, posterior dislocations may be the result of motor vehicle dashboard injury to the flexed knee. The frequent result of dislocation trauma is a damaged popliteal artery, said Dr. McDonough.

Determining the vascular status of a limb is imperative, he added. The amputation rate if repair occurs within 8 hours is 11%; otherwise, the amputation rate skyrockets to 86%, he said.

Between December 1993 and January 2005, Dr. McDonough and Dr. Edward M. Wojtys, professor of orthopaedic surgery at the University of Michigan, Ann Arbor, conducted a retrospective study of patients diagnosed with multiligamentous injury of the knee requiring surgical reconstruction. They identified 72 knees in 71 patients; there were 12 vascular injuries among nine men and three women. The causes were motor vehicle accidents (three cases); falls (four cases); sports (two cases); and assault, boating, and being pinned by a vehicle (one case each).

Physical exam and MRI were used to determine which ligaments were damaged, and these were confirmed at the time of surgical reconstruction. A total of four patients with vascular injury had abnormal physical exams on initial presentation and underwent emergent revascularization; eight patients had normal physical exams and normal pulses on initial exam.

Of those patients with normal initial physical exams, five were found to have intimal injury, and four underwent vascular bypass. Of three patients with both normal physical exams and normal arteriograms, two were found to have thrombosis secondary to large intimal flap lesions after ligament reconstruction. The remaining patients went on to have a pseudoaneurism requiring vascular reconstruction, said Dr. McDonough.

Dr. McDonough's findings contradict a recent study, which concluded that routine arteriography is not warranted in the treatment of these injuries, based on physical examination (J. Bone Joint Surg. Am. 2004;86:910–5).

Several authors have advocated selected arteriography based upon physical exam, Dr. McDonough said. However, there have been reports in the literature of popliteal artery injury secondary to knee dislocation presenting with normal distal pulses.

A 2002 metaanalysis of 116 articles concluded that abnormal pedal pulses are not sensitive enough to detect a surgical vascular injury and recommended liberal use of angiography, Dr. McDonough said (J. Trauma 2002;53:1109–14). The ankle brachial (arterial pressure) index has been proposed as a noninvasive and less costly test to assess arterial function, but a 1991 study concluded that the method's sensitivity was a poor runner-up to arteriography (Ann. Surg. 1991;214:737–41).

The amputation rate if vascular repair occurs within 8 hours is 11%; otherwise, the rate skyrockets to 86%. DR. MCDONOUGH

CHICAGO — Physical examination of the multidislocated knee is inadequate for determining the need for arteriography, according to a University of Michigan study.

“Routine arteriography is justified in multiligament injuries to the knee by the high incidence of popliteal artery injury, given the potentially devastating consequences of a delay in diagnosis and the relatively low morbidity of an arteriograph,” Dr. E. Barry McDonough told the annual meeting of the American Academy of Orthopaedic Surgeons.

Knee dislocation is rising in incidence due to increasing participation in sports, the popularity of all-terrain vehicles, and the boom in obesity, said Dr. McDonough, who is now with a group practice in Glen Ellyn, Ill.

Whereas anterior dislocations can be the result of a hyperextension injury, posterior dislocations may be the result of motor vehicle dashboard injury to the flexed knee. The frequent result of dislocation trauma is a damaged popliteal artery, said Dr. McDonough.

Determining the vascular status of a limb is imperative, he added. The amputation rate if repair occurs within 8 hours is 11%; otherwise, the amputation rate skyrockets to 86%, he said.

Between December 1993 and January 2005, Dr. McDonough and Dr. Edward M. Wojtys, professor of orthopaedic surgery at the University of Michigan, Ann Arbor, conducted a retrospective study of patients diagnosed with multiligamentous injury of the knee requiring surgical reconstruction. They identified 72 knees in 71 patients; there were 12 vascular injuries among nine men and three women. The causes were motor vehicle accidents (three cases); falls (four cases); sports (two cases); and assault, boating, and being pinned by a vehicle (one case each).

Physical exam and MRI were used to determine which ligaments were damaged, and these were confirmed at the time of surgical reconstruction. A total of four patients with vascular injury had abnormal physical exams on initial presentation and underwent emergent revascularization; eight patients had normal physical exams and normal pulses on initial exam.

Of those patients with normal initial physical exams, five were found to have intimal injury, and four underwent vascular bypass. Of three patients with both normal physical exams and normal arteriograms, two were found to have thrombosis secondary to large intimal flap lesions after ligament reconstruction. The remaining patients went on to have a pseudoaneurism requiring vascular reconstruction, said Dr. McDonough.

Dr. McDonough's findings contradict a recent study, which concluded that routine arteriography is not warranted in the treatment of these injuries, based on physical examination (J. Bone Joint Surg. Am. 2004;86:910–5).

Several authors have advocated selected arteriography based upon physical exam, Dr. McDonough said. However, there have been reports in the literature of popliteal artery injury secondary to knee dislocation presenting with normal distal pulses.

A 2002 metaanalysis of 116 articles concluded that abnormal pedal pulses are not sensitive enough to detect a surgical vascular injury and recommended liberal use of angiography, Dr. McDonough said (J. Trauma 2002;53:1109–14). The ankle brachial (arterial pressure) index has been proposed as a noninvasive and less costly test to assess arterial function, but a 1991 study concluded that the method's sensitivity was a poor runner-up to arteriography (Ann. Surg. 1991;214:737–41).

The amputation rate if vascular repair occurs within 8 hours is 11%; otherwise, the rate skyrockets to 86%. DR. MCDONOUGH

CHICAGO — Physical examination of the multidislocated knee is inadequate for determining the need for arteriography, according to a University of Michigan study.

“Routine arteriography is justified in multiligament injuries to the knee by the high incidence of popliteal artery injury, given the potentially devastating consequences of a delay in diagnosis and the relatively low morbidity of an arteriograph,” Dr. E. Barry McDonough told the annual meeting of the American Academy of Orthopaedic Surgeons.

Knee dislocation is rising in incidence due to increasing participation in sports, the popularity of all-terrain vehicles, and the boom in obesity, said Dr. McDonough, who is now with a group practice in Glen Ellyn, Ill.

Whereas anterior dislocations can be the result of a hyperextension injury, posterior dislocations may be the result of motor vehicle dashboard injury to the flexed knee. The frequent result of dislocation trauma is a damaged popliteal artery, said Dr. McDonough.

Determining the vascular status of a limb is imperative, he added. The amputation rate if repair occurs within 8 hours is 11%; otherwise, the amputation rate skyrockets to 86%, he said.

Between December 1993 and January 2005, Dr. McDonough and Dr. Edward M. Wojtys, professor of orthopaedic surgery at the University of Michigan, Ann Arbor, conducted a retrospective study of patients diagnosed with multiligamentous injury of the knee requiring surgical reconstruction. They identified 72 knees in 71 patients; there were 12 vascular injuries among nine men and three women. The causes were motor vehicle accidents (three cases); falls (four cases); sports (two cases); and assault, boating, and being pinned by a vehicle (one case each).

Physical exam and MRI were used to determine which ligaments were damaged, and these were confirmed at the time of surgical reconstruction. A total of four patients with vascular injury had abnormal physical exams on initial presentation and underwent emergent revascularization; eight patients had normal physical exams and normal pulses on initial exam.

Of those patients with normal initial physical exams, five were found to have intimal injury, and four underwent vascular bypass. Of three patients with both normal physical exams and normal arteriograms, two were found to have thrombosis secondary to large intimal flap lesions after ligament reconstruction. The remaining patients went on to have a pseudoaneurism requiring vascular reconstruction, said Dr. McDonough.

Dr. McDonough's findings contradict a recent study, which concluded that routine arteriography is not warranted in the treatment of these injuries, based on physical examination (J. Bone Joint Surg. Am. 2004;86:910–5).

Several authors have advocated selected arteriography based upon physical exam, Dr. McDonough said. However, there have been reports in the literature of popliteal artery injury secondary to knee dislocation presenting with normal distal pulses.

A 2002 metaanalysis of 116 articles concluded that abnormal pedal pulses are not sensitive enough to detect a surgical vascular injury and recommended liberal use of angiography, Dr. McDonough said (J. Trauma 2002;53:1109–14). The ankle brachial (arterial pressure) index has been proposed as a noninvasive and less costly test to assess arterial function, but a 1991 study concluded that the method's sensitivity was a poor runner-up to arteriography (Ann. Surg. 1991;214:737–41).

The amputation rate if vascular repair occurs within 8 hours is 11%; otherwise, the rate skyrockets to 86%. DR. MCDONOUGH