Bruce Jancin

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

LISBON – Pulsed dye laser therapy may be an attractive new option for treating nail psoriasis, according to Dr. Veronique Blatiere.

Nail psoriasis is challenging to treat because the psoriatic disease process damages the nails while they are still being formed. But Turkish investigators have reported positive results with three once-monthly pulsed dye laser (PDL) treatment sessions in a small uncontrolled patient series, Dr. Blatiere reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Yasemin Oram and coworkers at the American Hospital in Istanbul, Turkey, reported on five patients with nail psoriasis treated using PDL. The laser therapy was applied at 595 nm with a pulse duration of 1.5 milliseconds, a beam diameter of 7 mm, and an energy fluence of 8-10 J/cm². A treatment session was continued until a purple discoloration appeared.

The hypothesized mechanism of action involves destruction of the abnormal vasculature, according to the investigators (Dermatol. Surg. 2010;36:377-81).

Nail bed lesions, particularly onycholysis and subungual hyperkeratosis, responded to PDL better than did nail matrix lesions. After three treatment sessions, the average Nail Psoriasis Severity Index (NAPSI) score for nail bed lesions dropped from 14.8 to 8.

While the Turkish report is certainly encouraging, it should be viewed as a proof of concept pilot study, said Dr. Blatiere of Saint Eloi University Hospital in Montpellier, France. It needs confirmation with larger numbers of patients, a control arm, and blinded investigator assessment.

Dr. Blatiere noted that interest has been mounting in evaluating biologic agents for nail psoriasis. Favorable clinical experiences, albeit all of them open label, have recently been reported for the use of infliximab (J. Eur. Acad. Dermatol. Venereol. 2011;25:549-53); adalimumab (J. Eur. Acad. Dermatol. Venereol. 2010;24:530-4); ustekinumab (Arch. Dermatol. 2010;146:1315-6); and etanercept for nail psoriasis (J. Eur. Acad. Dermatol. Venereol. 2009;23:896-904).

But important questions remain about biologics for nail psoriasis, such as the appropriate duration of treatment, length of response, and whether they will help prevent psoriatic arthritis. And then there are the still incompletely answered questions regarding the long-term safety of the agents, as well as the issue of their considerable expense, Dr. Blatiere said.

She reported having no relevant financial disclosures.

LISBON – Pulsed dye laser therapy may be an attractive new option for treating nail psoriasis, according to Dr. Veronique Blatiere.

Nail psoriasis is challenging to treat because the psoriatic disease process damages the nails while they are still being formed. But Turkish investigators have reported positive results with three once-monthly pulsed dye laser (PDL) treatment sessions in a small uncontrolled patient series, Dr. Blatiere reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Yasemin Oram and coworkers at the American Hospital in Istanbul, Turkey, reported on five patients with nail psoriasis treated using PDL. The laser therapy was applied at 595 nm with a pulse duration of 1.5 milliseconds, a beam diameter of 7 mm, and an energy fluence of 8-10 J/cm². A treatment session was continued until a purple discoloration appeared.

The hypothesized mechanism of action involves destruction of the abnormal vasculature, according to the investigators (Dermatol. Surg. 2010;36:377-81).

Nail bed lesions, particularly onycholysis and subungual hyperkeratosis, responded to PDL better than did nail matrix lesions. After three treatment sessions, the average Nail Psoriasis Severity Index (NAPSI) score for nail bed lesions dropped from 14.8 to 8.

While the Turkish report is certainly encouraging, it should be viewed as a proof of concept pilot study, said Dr. Blatiere of Saint Eloi University Hospital in Montpellier, France. It needs confirmation with larger numbers of patients, a control arm, and blinded investigator assessment.

Dr. Blatiere noted that interest has been mounting in evaluating biologic agents for nail psoriasis. Favorable clinical experiences, albeit all of them open label, have recently been reported for the use of infliximab (J. Eur. Acad. Dermatol. Venereol. 2011;25:549-53); adalimumab (J. Eur. Acad. Dermatol. Venereol. 2010;24:530-4); ustekinumab (Arch. Dermatol. 2010;146:1315-6); and etanercept for nail psoriasis (J. Eur. Acad. Dermatol. Venereol. 2009;23:896-904).

But important questions remain about biologics for nail psoriasis, such as the appropriate duration of treatment, length of response, and whether they will help prevent psoriatic arthritis. And then there are the still incompletely answered questions regarding the long-term safety of the agents, as well as the issue of their considerable expense, Dr. Blatiere said.

She reported having no relevant financial disclosures.

LISBON – Pulsed dye laser therapy may be an attractive new option for treating nail psoriasis, according to Dr. Veronique Blatiere.

Nail psoriasis is challenging to treat because the psoriatic disease process damages the nails while they are still being formed. But Turkish investigators have reported positive results with three once-monthly pulsed dye laser (PDL) treatment sessions in a small uncontrolled patient series, Dr. Blatiere reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Yasemin Oram and coworkers at the American Hospital in Istanbul, Turkey, reported on five patients with nail psoriasis treated using PDL. The laser therapy was applied at 595 nm with a pulse duration of 1.5 milliseconds, a beam diameter of 7 mm, and an energy fluence of 8-10 J/cm². A treatment session was continued until a purple discoloration appeared.

The hypothesized mechanism of action involves destruction of the abnormal vasculature, according to the investigators (Dermatol. Surg. 2010;36:377-81).

Nail bed lesions, particularly onycholysis and subungual hyperkeratosis, responded to PDL better than did nail matrix lesions. After three treatment sessions, the average Nail Psoriasis Severity Index (NAPSI) score for nail bed lesions dropped from 14.8 to 8.

While the Turkish report is certainly encouraging, it should be viewed as a proof of concept pilot study, said Dr. Blatiere of Saint Eloi University Hospital in Montpellier, France. It needs confirmation with larger numbers of patients, a control arm, and blinded investigator assessment.

Dr. Blatiere noted that interest has been mounting in evaluating biologic agents for nail psoriasis. Favorable clinical experiences, albeit all of them open label, have recently been reported for the use of infliximab (J. Eur. Acad. Dermatol. Venereol. 2011;25:549-53); adalimumab (J. Eur. Acad. Dermatol. Venereol. 2010;24:530-4); ustekinumab (Arch. Dermatol. 2010;146:1315-6); and etanercept for nail psoriasis (J. Eur. Acad. Dermatol. Venereol. 2009;23:896-904).

But important questions remain about biologics for nail psoriasis, such as the appropriate duration of treatment, length of response, and whether they will help prevent psoriatic arthritis. And then there are the still incompletely answered questions regarding the long-term safety of the agents, as well as the issue of their considerable expense, Dr. Blatiere said.

She reported having no relevant financial disclosures.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN DIEGO – Teriparatide is gaining traction as an off-label therapy to speed fracture repair and promote healing of delayed union and nonunion fractures.

At a session expressly devoted to anabolic agents for fracture repair at the annual meeting of the American Society for Bone and Mineral Research, Dr. Robert Marcus said he is aware of numerous anecdotal reports of successful use of teriparatide (Forteo) to accelerate fracture healing and shorten return-to-play time in high-profile professional and elite collegiate athletes.

Although HIPAA regulations prevent him from naming any of the American athletes involved, Dr. Marcus said, HIPAA doesn't apply to the Italian soccer superstar Francesco Totti.

Totti, a prolific goal scorer known as Il Bimbo d’Oro (The Golden Boy) and Il Gladiatore, suffered a serious combined tibia/fibula fracture in the spring of 2006. The injury was expected to keep him out of action for the entire World Cup tournament that summer, and for well beyond. But he was placed on teriparatide almost immediately after the fracture. He played every game of the series, Italy won the 2006 World Cup, and Totti was named to the tournament’s all-star team.

Dr. Marcus, professor of medicine emeritus at Stanford (Calif.) University and a former Eli Lilly employee, made it clear he is not promoting the off-label use of teriparatide to accelerate fracture healing. He recalled that when Eli Lilly approached the Food and Drug Administration with the aim of gaining this additional indication, the agency required as an initial proof-of-concept study a randomized, double-blind, placebo-controlled trial conducted in postmenopausal women with a distal radial fracture incurred within the previous 10 days.

That multicenter study in 102 women with Colles’ fracture showed a highly significantly shorter time to healing with 8 weeks of daily teriparatide at the standard 20-mcg dose used for osteoporosis therapy than with placebo, although the 40-mcg dose unexpectedly proved ineffective (J. Bone Miner. Res. 2010;25:404-14).

But Colles’ fracture isn’t really a good test of the therapy, according to Dr. Marcus, because it doesn’t involve weight-bearing bones. Where an agent for acceleration of fracture repair would really be a boon in young people with, say, tibia fractures caused by motorcycle or skateboarding accidents. Such fractures often fail to heal successfully with conservative treatment in a reasonable time and eventually require surgical fixation and metal hardware, the endocrinologist said.

Dr. Marcus noted that Dr. Susan V. Bukata, an orthopedic oncologist at the University of Rochester (N.Y.), has previously reported on 145 patients with painful delayed/nonunion fractures treated with daily teriparatide at the standard 20-mcg dose. Within 12 weeks of starting therapy, 93% of patients in this retrospective observational series showed full radiographic and clinical healing. Another 4% had partial radiographic union that functioned clinically as a healed fracture. Only 3% of patients remained unimproved after 12 weeks of teriparatide. Dr. Bukata’s series has grown to more than 500 patients treated for delayed/nonunion fractures; the data are now being analyzed.

In order to gain an FDA indication for acceleration of fracture healing, however, it will be essential to conduct a randomized controlled trial involving fractures at clinically appropriate sites. Quantitative assessment of radiographic endpoints with CT and/or MRI will be a must, as will inclusion of functional end points such as pain reduction, muscle strength, ambulation, and return to work or daily activities. The FDA’s concern about osteosarcomas and other bone tumors seen in rats on lifelong very-high-dose teriparatide will be an issue, Dr. Marcus predicted.

Elsewhere at the meeting, Dr. Peter Peichl presented a study that fulfilled many of the requirements of a pivotal trial, albeit using the naturally occurring parathyroid hormone (PTH) containing 84 amino acids rather than its close relative, teriparatide.

The study involved 65 elderly postmenopausal women hospitalized for painful pubic bone fractures to be treated without surgery. In all, 21 patients were randomized to once-daily injection of 100 mcg of PTH. The 44 women who didn’t receive PTH served as controls. All participants received daily calcium and vitamin D supplements.

The 21 patients in the PTH-treated group showed CT-confirmed healing of their pubic bone fractures at a mean of 7.8 weeks, significantly faster than the 12.6 weeks in controls. At 8 weeks, all subjects in the PTH study arm were healed, as were only 4 of 44 controls. In addition, the PTH-treated patients showed bigger and faster improvements on a pain visual analog scale and on the Timed Up and Go functional assessment, reported Dr. Peichl of Evangelical Hospital Vienna.

Dr. Peichl declared having no financial conflicts. Dr. Marcus is a consultant to and on the speaker’s bureau for Eli Lilly.

SAN DIEGO – Teriparatide is gaining traction as an off-label therapy to speed fracture repair and promote healing of delayed union and nonunion fractures.

At a session expressly devoted to anabolic agents for fracture repair at the annual meeting of the American Society for Bone and Mineral Research, Dr. Robert Marcus said he is aware of numerous anecdotal reports of successful use of teriparatide (Forteo) to accelerate fracture healing and shorten return-to-play time in high-profile professional and elite collegiate athletes.

Although HIPAA regulations prevent him from naming any of the American athletes involved, Dr. Marcus said, HIPAA doesn't apply to the Italian soccer superstar Francesco Totti.

Totti, a prolific goal scorer known as Il Bimbo d’Oro (The Golden Boy) and Il Gladiatore, suffered a serious combined tibia/fibula fracture in the spring of 2006. The injury was expected to keep him out of action for the entire World Cup tournament that summer, and for well beyond. But he was placed on teriparatide almost immediately after the fracture. He played every game of the series, Italy won the 2006 World Cup, and Totti was named to the tournament’s all-star team.

Dr. Marcus, professor of medicine emeritus at Stanford (Calif.) University and a former Eli Lilly employee, made it clear he is not promoting the off-label use of teriparatide to accelerate fracture healing. He recalled that when Eli Lilly approached the Food and Drug Administration with the aim of gaining this additional indication, the agency required as an initial proof-of-concept study a randomized, double-blind, placebo-controlled trial conducted in postmenopausal women with a distal radial fracture incurred within the previous 10 days.

That multicenter study in 102 women with Colles’ fracture showed a highly significantly shorter time to healing with 8 weeks of daily teriparatide at the standard 20-mcg dose used for osteoporosis therapy than with placebo, although the 40-mcg dose unexpectedly proved ineffective (J. Bone Miner. Res. 2010;25:404-14).

But Colles’ fracture isn’t really a good test of the therapy, according to Dr. Marcus, because it doesn’t involve weight-bearing bones. Where an agent for acceleration of fracture repair would really be a boon in young people with, say, tibia fractures caused by motorcycle or skateboarding accidents. Such fractures often fail to heal successfully with conservative treatment in a reasonable time and eventually require surgical fixation and metal hardware, the endocrinologist said.

Dr. Marcus noted that Dr. Susan V. Bukata, an orthopedic oncologist at the University of Rochester (N.Y.), has previously reported on 145 patients with painful delayed/nonunion fractures treated with daily teriparatide at the standard 20-mcg dose. Within 12 weeks of starting therapy, 93% of patients in this retrospective observational series showed full radiographic and clinical healing. Another 4% had partial radiographic union that functioned clinically as a healed fracture. Only 3% of patients remained unimproved after 12 weeks of teriparatide. Dr. Bukata’s series has grown to more than 500 patients treated for delayed/nonunion fractures; the data are now being analyzed.

In order to gain an FDA indication for acceleration of fracture healing, however, it will be essential to conduct a randomized controlled trial involving fractures at clinically appropriate sites. Quantitative assessment of radiographic endpoints with CT and/or MRI will be a must, as will inclusion of functional end points such as pain reduction, muscle strength, ambulation, and return to work or daily activities. The FDA’s concern about osteosarcomas and other bone tumors seen in rats on lifelong very-high-dose teriparatide will be an issue, Dr. Marcus predicted.

Elsewhere at the meeting, Dr. Peter Peichl presented a study that fulfilled many of the requirements of a pivotal trial, albeit using the naturally occurring parathyroid hormone (PTH) containing 84 amino acids rather than its close relative, teriparatide.

The study involved 65 elderly postmenopausal women hospitalized for painful pubic bone fractures to be treated without surgery. In all, 21 patients were randomized to once-daily injection of 100 mcg of PTH. The 44 women who didn’t receive PTH served as controls. All participants received daily calcium and vitamin D supplements.

The 21 patients in the PTH-treated group showed CT-confirmed healing of their pubic bone fractures at a mean of 7.8 weeks, significantly faster than the 12.6 weeks in controls. At 8 weeks, all subjects in the PTH study arm were healed, as were only 4 of 44 controls. In addition, the PTH-treated patients showed bigger and faster improvements on a pain visual analog scale and on the Timed Up and Go functional assessment, reported Dr. Peichl of Evangelical Hospital Vienna.

Dr. Peichl declared having no financial conflicts. Dr. Marcus is a consultant to and on the speaker’s bureau for Eli Lilly.

SAN DIEGO – Teriparatide is gaining traction as an off-label therapy to speed fracture repair and promote healing of delayed union and nonunion fractures.

At a session expressly devoted to anabolic agents for fracture repair at the annual meeting of the American Society for Bone and Mineral Research, Dr. Robert Marcus said he is aware of numerous anecdotal reports of successful use of teriparatide (Forteo) to accelerate fracture healing and shorten return-to-play time in high-profile professional and elite collegiate athletes.

Although HIPAA regulations prevent him from naming any of the American athletes involved, Dr. Marcus said, HIPAA doesn't apply to the Italian soccer superstar Francesco Totti.

Totti, a prolific goal scorer known as Il Bimbo d’Oro (The Golden Boy) and Il Gladiatore, suffered a serious combined tibia/fibula fracture in the spring of 2006. The injury was expected to keep him out of action for the entire World Cup tournament that summer, and for well beyond. But he was placed on teriparatide almost immediately after the fracture. He played every game of the series, Italy won the 2006 World Cup, and Totti was named to the tournament’s all-star team.

Dr. Marcus, professor of medicine emeritus at Stanford (Calif.) University and a former Eli Lilly employee, made it clear he is not promoting the off-label use of teriparatide to accelerate fracture healing. He recalled that when Eli Lilly approached the Food and Drug Administration with the aim of gaining this additional indication, the agency required as an initial proof-of-concept study a randomized, double-blind, placebo-controlled trial conducted in postmenopausal women with a distal radial fracture incurred within the previous 10 days.

That multicenter study in 102 women with Colles’ fracture showed a highly significantly shorter time to healing with 8 weeks of daily teriparatide at the standard 20-mcg dose used for osteoporosis therapy than with placebo, although the 40-mcg dose unexpectedly proved ineffective (J. Bone Miner. Res. 2010;25:404-14).

But Colles’ fracture isn’t really a good test of the therapy, according to Dr. Marcus, because it doesn’t involve weight-bearing bones. Where an agent for acceleration of fracture repair would really be a boon in young people with, say, tibia fractures caused by motorcycle or skateboarding accidents. Such fractures often fail to heal successfully with conservative treatment in a reasonable time and eventually require surgical fixation and metal hardware, the endocrinologist said.

Dr. Marcus noted that Dr. Susan V. Bukata, an orthopedic oncologist at the University of Rochester (N.Y.), has previously reported on 145 patients with painful delayed/nonunion fractures treated with daily teriparatide at the standard 20-mcg dose. Within 12 weeks of starting therapy, 93% of patients in this retrospective observational series showed full radiographic and clinical healing. Another 4% had partial radiographic union that functioned clinically as a healed fracture. Only 3% of patients remained unimproved after 12 weeks of teriparatide. Dr. Bukata’s series has grown to more than 500 patients treated for delayed/nonunion fractures; the data are now being analyzed.

In order to gain an FDA indication for acceleration of fracture healing, however, it will be essential to conduct a randomized controlled trial involving fractures at clinically appropriate sites. Quantitative assessment of radiographic endpoints with CT and/or MRI will be a must, as will inclusion of functional end points such as pain reduction, muscle strength, ambulation, and return to work or daily activities. The FDA’s concern about osteosarcomas and other bone tumors seen in rats on lifelong very-high-dose teriparatide will be an issue, Dr. Marcus predicted.

Elsewhere at the meeting, Dr. Peter Peichl presented a study that fulfilled many of the requirements of a pivotal trial, albeit using the naturally occurring parathyroid hormone (PTH) containing 84 amino acids rather than its close relative, teriparatide.

The study involved 65 elderly postmenopausal women hospitalized for painful pubic bone fractures to be treated without surgery. In all, 21 patients were randomized to once-daily injection of 100 mcg of PTH. The 44 women who didn’t receive PTH served as controls. All participants received daily calcium and vitamin D supplements.

The 21 patients in the PTH-treated group showed CT-confirmed healing of their pubic bone fractures at a mean of 7.8 weeks, significantly faster than the 12.6 weeks in controls. At 8 weeks, all subjects in the PTH study arm were healed, as were only 4 of 44 controls. In addition, the PTH-treated patients showed bigger and faster improvements on a pain visual analog scale and on the Timed Up and Go functional assessment, reported Dr. Peichl of Evangelical Hospital Vienna.

Dr. Peichl declared having no financial conflicts. Dr. Marcus is a consultant to and on the speaker’s bureau for Eli Lilly.

LISBON – Psoriasis and diabetes are expensive diseases, and patients with both conditions experience a synergistic increase in health care utilization and costs that is significantly greater than the incremental economic burden imposed by each disease individually.

In other words, patients with comorbid psoriasis and diabetes have more hospitalizations and outpatient visits over the course of a year than would be expected simply from adding together the increased use typical of patients with psoriasis to that of patients with diabetes, compared with health care use by individuals with neither condition, Dr. Frank Zhang reported at the annual congress of the European Academy of Dermatology and Venereology.

This is an observation with important implications for health economics. These are two common diseases. Psoriasis affects 2%-3% of the world’s population, with 260,000 new cases arising per year in the United States alone. Psoriasis predisposes to insulin resistance, and psoriasis patients have a one-third greater risk of diabetes than the general population, noted Dr. Zhang of Celgene Corporation, Summit, N.J.

Because the economic impact of having both diseases had not been addressed, he and his colleagues conducted a retrospective study of 106,128 patient pairs matched for age and gender, one member of each pair having psoriasis and the other free of the disease. The patients were drawn from the Thomson Reuters MarketScan Research Databases for 2004 through June 2009.

Sixteen percent of the psoriasis patients had diabetes, significantly greater than the 13% with diabetes in the control group.

Psoriasis patients with diabetes averaged 17 more hospitalizations per 100 patient-years and 5.8 more outpatient visits per year than did psoriasis patients without diabetes. And patients with diabetes with psoriasis averaged five more hospitalizations per 100 patient-years and 6.3 additional outpatient visits per year, compared with non–psoriatic patients with diabetes.

The most likely explanation for this synergistic health care burden in the dual-diagnosis patient lies in the complexity entailed in managing the two diseases simultaneously, said Dr. Zhang.

Total annual health care costs in patients with both psoriasis and diabetes averaged $19,536, compared with $13,589 for psoriasis-free patients with diabetes and $5,539 in those who had psoriasis but not diabetes.

The study was funded by Celgene, where Dr. Zhang is employed.

LISBON – Psoriasis and diabetes are expensive diseases, and patients with both conditions experience a synergistic increase in health care utilization and costs that is significantly greater than the incremental economic burden imposed by each disease individually.

In other words, patients with comorbid psoriasis and diabetes have more hospitalizations and outpatient visits over the course of a year than would be expected simply from adding together the increased use typical of patients with psoriasis to that of patients with diabetes, compared with health care use by individuals with neither condition, Dr. Frank Zhang reported at the annual congress of the European Academy of Dermatology and Venereology.

This is an observation with important implications for health economics. These are two common diseases. Psoriasis affects 2%-3% of the world’s population, with 260,000 new cases arising per year in the United States alone. Psoriasis predisposes to insulin resistance, and psoriasis patients have a one-third greater risk of diabetes than the general population, noted Dr. Zhang of Celgene Corporation, Summit, N.J.

Because the economic impact of having both diseases had not been addressed, he and his colleagues conducted a retrospective study of 106,128 patient pairs matched for age and gender, one member of each pair having psoriasis and the other free of the disease. The patients were drawn from the Thomson Reuters MarketScan Research Databases for 2004 through June 2009.

Sixteen percent of the psoriasis patients had diabetes, significantly greater than the 13% with diabetes in the control group.

Psoriasis patients with diabetes averaged 17 more hospitalizations per 100 patient-years and 5.8 more outpatient visits per year than did psoriasis patients without diabetes. And patients with diabetes with psoriasis averaged five more hospitalizations per 100 patient-years and 6.3 additional outpatient visits per year, compared with non–psoriatic patients with diabetes.

The most likely explanation for this synergistic health care burden in the dual-diagnosis patient lies in the complexity entailed in managing the two diseases simultaneously, said Dr. Zhang.

Total annual health care costs in patients with both psoriasis and diabetes averaged $19,536, compared with $13,589 for psoriasis-free patients with diabetes and $5,539 in those who had psoriasis but not diabetes.

The study was funded by Celgene, where Dr. Zhang is employed.

LISBON – Psoriasis and diabetes are expensive diseases, and patients with both conditions experience a synergistic increase in health care utilization and costs that is significantly greater than the incremental economic burden imposed by each disease individually.

In other words, patients with comorbid psoriasis and diabetes have more hospitalizations and outpatient visits over the course of a year than would be expected simply from adding together the increased use typical of patients with psoriasis to that of patients with diabetes, compared with health care use by individuals with neither condition, Dr. Frank Zhang reported at the annual congress of the European Academy of Dermatology and Venereology.

This is an observation with important implications for health economics. These are two common diseases. Psoriasis affects 2%-3% of the world’s population, with 260,000 new cases arising per year in the United States alone. Psoriasis predisposes to insulin resistance, and psoriasis patients have a one-third greater risk of diabetes than the general population, noted Dr. Zhang of Celgene Corporation, Summit, N.J.

Because the economic impact of having both diseases had not been addressed, he and his colleagues conducted a retrospective study of 106,128 patient pairs matched for age and gender, one member of each pair having psoriasis and the other free of the disease. The patients were drawn from the Thomson Reuters MarketScan Research Databases for 2004 through June 2009.

Sixteen percent of the psoriasis patients had diabetes, significantly greater than the 13% with diabetes in the control group.

Psoriasis patients with diabetes averaged 17 more hospitalizations per 100 patient-years and 5.8 more outpatient visits per year than did psoriasis patients without diabetes. And patients with diabetes with psoriasis averaged five more hospitalizations per 100 patient-years and 6.3 additional outpatient visits per year, compared with non–psoriatic patients with diabetes.

The most likely explanation for this synergistic health care burden in the dual-diagnosis patient lies in the complexity entailed in managing the two diseases simultaneously, said Dr. Zhang.

Total annual health care costs in patients with both psoriasis and diabetes averaged $19,536, compared with $13,589 for psoriasis-free patients with diabetes and $5,539 in those who had psoriasis but not diabetes.

The study was funded by Celgene, where Dr. Zhang is employed.

SAN ANTONIO – A phase III trial of an adjuvant breast cancer vaccine will begin enrollment before the end of 2011 as a result of favorable 5-year efficacy and safety data in a phase II study.

In updated phase II results, disease-free survival at a median follow-up of 60 months was 95.9% in 53 patients who received the E75 vaccine with multiple booster inoculations, significantly better than the 79.7% figure in 79 controls (P = .016), Dr. Timothy J. Vreeland reported at the San Antonio Breast Cancer Symposium.

The vaccine, known as NeuVax, is composed of the E75 peptide, which is derived from human epidermal growth factor receptor 2 (HER2), mixed with granulocyte macrophage colony-stimulating factor (GM-CSF). The vaccine has previously been shown to stimulate cytotoxic T cells to specifically target cells expressing HER2.

As a result of lessons learned in the randomized phase II study, the phase III trial will be restricted to patients with lymph node–positive tumors who are clinically disease-free after completing standard therapy. Only patients with low levels of HER2 expression, meaning immunohistochemistry 1+ or 2+, will be eligible.

The E75 vaccine was initially given as an intradermal injection once a month for 6 months. Because of waning immunity noted during phase I and II testing, however, a booster immunization program was initiated. It consists of a booster injection once every 6 months. The booster program will be routine in the phase III trial.

The overall phase II study population consisted of 187 patients with node-positive or high-risk node-negative tumors expressing any level of HER2. The median 5-year disease-free survival in the 108 patients in the vaccine arm was 89.4%, compared with 79.7% in controls, a nonsignificant difference. But the vaccine arm included 55 women who didn’t receive booster immunizations. When they were excluded, the 5-year disease-free survival rate climbed to 95.9%, according to Dr. Vreeland, a U.S. Army captain at San Antonio Military Medical Center.

The E75 vaccine has been very well tolerated. A total of 70%-85% of local and systemic toxicities in both the primary vaccination series and the booster inoculations have been grade I, with the remainder grade II. Seven of 53 patients (13%) in the booster program developed grade II delayed urticarial reactions at a median of 9 days post inoculation.

The phase III trial is called PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment).

The NeuVax vaccine has been licensed by the U.S. military to Galena Biopharma. Dr. Vreeland declared having no relevant financial disclosures.

SAN ANTONIO – A phase III trial of an adjuvant breast cancer vaccine will begin enrollment before the end of 2011 as a result of favorable 5-year efficacy and safety data in a phase II study.

In updated phase II results, disease-free survival at a median follow-up of 60 months was 95.9% in 53 patients who received the E75 vaccine with multiple booster inoculations, significantly better than the 79.7% figure in 79 controls (P = .016), Dr. Timothy J. Vreeland reported at the San Antonio Breast Cancer Symposium.

The vaccine, known as NeuVax, is composed of the E75 peptide, which is derived from human epidermal growth factor receptor 2 (HER2), mixed with granulocyte macrophage colony-stimulating factor (GM-CSF). The vaccine has previously been shown to stimulate cytotoxic T cells to specifically target cells expressing HER2.

As a result of lessons learned in the randomized phase II study, the phase III trial will be restricted to patients with lymph node–positive tumors who are clinically disease-free after completing standard therapy. Only patients with low levels of HER2 expression, meaning immunohistochemistry 1+ or 2+, will be eligible.

The E75 vaccine was initially given as an intradermal injection once a month for 6 months. Because of waning immunity noted during phase I and II testing, however, a booster immunization program was initiated. It consists of a booster injection once every 6 months. The booster program will be routine in the phase III trial.

The overall phase II study population consisted of 187 patients with node-positive or high-risk node-negative tumors expressing any level of HER2. The median 5-year disease-free survival in the 108 patients in the vaccine arm was 89.4%, compared with 79.7% in controls, a nonsignificant difference. But the vaccine arm included 55 women who didn’t receive booster immunizations. When they were excluded, the 5-year disease-free survival rate climbed to 95.9%, according to Dr. Vreeland, a U.S. Army captain at San Antonio Military Medical Center.

The E75 vaccine has been very well tolerated. A total of 70%-85% of local and systemic toxicities in both the primary vaccination series and the booster inoculations have been grade I, with the remainder grade II. Seven of 53 patients (13%) in the booster program developed grade II delayed urticarial reactions at a median of 9 days post inoculation.

The phase III trial is called PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment).

The NeuVax vaccine has been licensed by the U.S. military to Galena Biopharma. Dr. Vreeland declared having no relevant financial disclosures.

SAN ANTONIO – A phase III trial of an adjuvant breast cancer vaccine will begin enrollment before the end of 2011 as a result of favorable 5-year efficacy and safety data in a phase II study.

In updated phase II results, disease-free survival at a median follow-up of 60 months was 95.9% in 53 patients who received the E75 vaccine with multiple booster inoculations, significantly better than the 79.7% figure in 79 controls (P = .016), Dr. Timothy J. Vreeland reported at the San Antonio Breast Cancer Symposium.

The vaccine, known as NeuVax, is composed of the E75 peptide, which is derived from human epidermal growth factor receptor 2 (HER2), mixed with granulocyte macrophage colony-stimulating factor (GM-CSF). The vaccine has previously been shown to stimulate cytotoxic T cells to specifically target cells expressing HER2.

As a result of lessons learned in the randomized phase II study, the phase III trial will be restricted to patients with lymph node–positive tumors who are clinically disease-free after completing standard therapy. Only patients with low levels of HER2 expression, meaning immunohistochemistry 1+ or 2+, will be eligible.

The E75 vaccine was initially given as an intradermal injection once a month for 6 months. Because of waning immunity noted during phase I and II testing, however, a booster immunization program was initiated. It consists of a booster injection once every 6 months. The booster program will be routine in the phase III trial.

The overall phase II study population consisted of 187 patients with node-positive or high-risk node-negative tumors expressing any level of HER2. The median 5-year disease-free survival in the 108 patients in the vaccine arm was 89.4%, compared with 79.7% in controls, a nonsignificant difference. But the vaccine arm included 55 women who didn’t receive booster immunizations. When they were excluded, the 5-year disease-free survival rate climbed to 95.9%, according to Dr. Vreeland, a U.S. Army captain at San Antonio Military Medical Center.

The E75 vaccine has been very well tolerated. A total of 70%-85% of local and systemic toxicities in both the primary vaccination series and the booster inoculations have been grade I, with the remainder grade II. Seven of 53 patients (13%) in the booster program developed grade II delayed urticarial reactions at a median of 9 days post inoculation.

The phase III trial is called PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment).

The NeuVax vaccine has been licensed by the U.S. military to Galena Biopharma. Dr. Vreeland declared having no relevant financial disclosures.

LISBON – A novel, intradermally-injected, monophasic hyaluronic acid filler known as Belotero Intense outperformed Perlane for the treatment of moderate to deep nasolabial folds in a 12-month, double-blind, randomized trial, according to Dr. Martina Kerscher.

Merz Pharmaceuticals’ Belotero Intense is manufactured using a proprietary Cohesive Polydensified Matrix technology. The resultant product, a monophasic, polydensified hyaluronic acid filler, was designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than achievable with biphasic hyaluronic acid fillers, said Dr. Kerscher at the annual congress of the European Academy of Dermatology and Venereology.

She reported on 20 patients aged 35-65 years, with nasolabial folds (NLFs) that were grades 3-4 on a 5-point scale, meaning the defects were either moderately deep or very long and deep. Participants were randomized double-blindly to a single intradermal injection on one side of the face with Belotero Intense, while the NLFs on the other side of the face were treated with Medicis Aesthetics’ Perlane, a biphasic hyaluronic acid filler. Both products are gels of nonanimal origin. No touch-ups were permitted during the 12 months of follow-up.

Physician- and patient-rated scores on the Wrinkle Severity Rating Scale improved with both products; however, the degree of improvement was significantly greater through 24 weeks with the monophasic hyaluronic acid filler.

Belotero Intense is designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than is achievable with biphasic hyaluronic acid fillers, said Dr. Martina Kerscher.

Mean scores on the 0-4 scale went from a baseline of 4.0 to 2.4 with the biphasic filler and to 2.1 with the monophasic filler at week 2; at week 24, mean scores were 2.7 for the biphasic filler, compared with 2.4 for the monophasic filler. At week 48, however, both products showed similar effects.

Investigators and patients gave the monophasic hyaluronic acid gel higher marks on the Global Aesthetic Improvement Scale through 24 weeks. After week 24, scores for the two products merged, reported Dr. Kerscher of the University of Hamburg (Germany) division of cosmetic science.

Standardized measurements of wrinkle depth for the Belotero Intense-treated NLFs went from a baseline of 271 mm to 172 mm at week 2, 194 mm at week 24, and 213 mm at week 48. Depth of the Perlane-treated NLFs improved from 222 mm at baseline to 152 mm at week 2, 177 mm at week 24, and 184 mm at week 48. This translated to a 28% reduction in wrinkle depth at week 24 in the monophasic filler-treated lesions, compared with a 20% decrease in the biphasic filler-treated folds. The week 48 improvement was 21% in the monophasic- and 17% in the biphasic-treated NLFs.

Self-rated patient satisfaction was scored on a 0-10 scale, with a lower score showing a higher level of satisfaction. From a baseline of 7.0, scores improved to 2.3 for the biphasic filler and 2.1 for the monophasic filler at week 2, to 4.9 for biphasic and 3.8 for monophasic at week 24, and to 6.7 for biphasic and 5.7 for monophasic at week 48.

Of note, the blinded patients consistently recorded significantly less injection site pain with the monophasic hyaluronic acid filler.

Belotero Intense is licensed in the United Kingdom and several European countries as a medical device for the correction of deep folds and for volume augmentation. A sister product, Belotero Balance, earned marketing approval from the Food and Drug Administration in November 2011 for correction of moderate to severe wrinkles and folds. Belotero Intense is intended for deeper injection and correction of more pronounced defects than is Belotero Balance.

Merz is seeking FDA approval of Belotero Intense.

The study presented by Dr. Kerscher was sponsored by Merz, which markets the Belotero product line. She is a consultant to the company.

LISBON – A novel, intradermally-injected, monophasic hyaluronic acid filler known as Belotero Intense outperformed Perlane for the treatment of moderate to deep nasolabial folds in a 12-month, double-blind, randomized trial, according to Dr. Martina Kerscher.

Merz Pharmaceuticals’ Belotero Intense is manufactured using a proprietary Cohesive Polydensified Matrix technology. The resultant product, a monophasic, polydensified hyaluronic acid filler, was designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than achievable with biphasic hyaluronic acid fillers, said Dr. Kerscher at the annual congress of the European Academy of Dermatology and Venereology.

She reported on 20 patients aged 35-65 years, with nasolabial folds (NLFs) that were grades 3-4 on a 5-point scale, meaning the defects were either moderately deep or very long and deep. Participants were randomized double-blindly to a single intradermal injection on one side of the face with Belotero Intense, while the NLFs on the other side of the face were treated with Medicis Aesthetics’ Perlane, a biphasic hyaluronic acid filler. Both products are gels of nonanimal origin. No touch-ups were permitted during the 12 months of follow-up.

Physician- and patient-rated scores on the Wrinkle Severity Rating Scale improved with both products; however, the degree of improvement was significantly greater through 24 weeks with the monophasic hyaluronic acid filler.

Belotero Intense is designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than is achievable with biphasic hyaluronic acid fillers, said Dr. Martina Kerscher.

Mean scores on the 0-4 scale went from a baseline of 4.0 to 2.4 with the biphasic filler and to 2.1 with the monophasic filler at week 2; at week 24, mean scores were 2.7 for the biphasic filler, compared with 2.4 for the monophasic filler. At week 48, however, both products showed similar effects.

Investigators and patients gave the monophasic hyaluronic acid gel higher marks on the Global Aesthetic Improvement Scale through 24 weeks. After week 24, scores for the two products merged, reported Dr. Kerscher of the University of Hamburg (Germany) division of cosmetic science.

Standardized measurements of wrinkle depth for the Belotero Intense-treated NLFs went from a baseline of 271 mm to 172 mm at week 2, 194 mm at week 24, and 213 mm at week 48. Depth of the Perlane-treated NLFs improved from 222 mm at baseline to 152 mm at week 2, 177 mm at week 24, and 184 mm at week 48. This translated to a 28% reduction in wrinkle depth at week 24 in the monophasic filler-treated lesions, compared with a 20% decrease in the biphasic filler-treated folds. The week 48 improvement was 21% in the monophasic- and 17% in the biphasic-treated NLFs.

Self-rated patient satisfaction was scored on a 0-10 scale, with a lower score showing a higher level of satisfaction. From a baseline of 7.0, scores improved to 2.3 for the biphasic filler and 2.1 for the monophasic filler at week 2, to 4.9 for biphasic and 3.8 for monophasic at week 24, and to 6.7 for biphasic and 5.7 for monophasic at week 48.

Of note, the blinded patients consistently recorded significantly less injection site pain with the monophasic hyaluronic acid filler.

Belotero Intense is licensed in the United Kingdom and several European countries as a medical device for the correction of deep folds and for volume augmentation. A sister product, Belotero Balance, earned marketing approval from the Food and Drug Administration in November 2011 for correction of moderate to severe wrinkles and folds. Belotero Intense is intended for deeper injection and correction of more pronounced defects than is Belotero Balance.

Merz is seeking FDA approval of Belotero Intense.

The study presented by Dr. Kerscher was sponsored by Merz, which markets the Belotero product line. She is a consultant to the company.

LISBON – A novel, intradermally-injected, monophasic hyaluronic acid filler known as Belotero Intense outperformed Perlane for the treatment of moderate to deep nasolabial folds in a 12-month, double-blind, randomized trial, according to Dr. Martina Kerscher.

Merz Pharmaceuticals’ Belotero Intense is manufactured using a proprietary Cohesive Polydensified Matrix technology. The resultant product, a monophasic, polydensified hyaluronic acid filler, was designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than achievable with biphasic hyaluronic acid fillers, said Dr. Kerscher at the annual congress of the European Academy of Dermatology and Venereology.

She reported on 20 patients aged 35-65 years, with nasolabial folds (NLFs) that were grades 3-4 on a 5-point scale, meaning the defects were either moderately deep or very long and deep. Participants were randomized double-blindly to a single intradermal injection on one side of the face with Belotero Intense, while the NLFs on the other side of the face were treated with Medicis Aesthetics’ Perlane, a biphasic hyaluronic acid filler. Both products are gels of nonanimal origin. No touch-ups were permitted during the 12 months of follow-up.

Physician- and patient-rated scores on the Wrinkle Severity Rating Scale improved with both products; however, the degree of improvement was significantly greater through 24 weeks with the monophasic hyaluronic acid filler.

Belotero Intense is designed to provide greater elasticity, less risk of lumping, and longer-lasting improvements than is achievable with biphasic hyaluronic acid fillers, said Dr. Martina Kerscher.

Mean scores on the 0-4 scale went from a baseline of 4.0 to 2.4 with the biphasic filler and to 2.1 with the monophasic filler at week 2; at week 24, mean scores were 2.7 for the biphasic filler, compared with 2.4 for the monophasic filler. At week 48, however, both products showed similar effects.

Investigators and patients gave the monophasic hyaluronic acid gel higher marks on the Global Aesthetic Improvement Scale through 24 weeks. After week 24, scores for the two products merged, reported Dr. Kerscher of the University of Hamburg (Germany) division of cosmetic science.

Standardized measurements of wrinkle depth for the Belotero Intense-treated NLFs went from a baseline of 271 mm to 172 mm at week 2, 194 mm at week 24, and 213 mm at week 48. Depth of the Perlane-treated NLFs improved from 222 mm at baseline to 152 mm at week 2, 177 mm at week 24, and 184 mm at week 48. This translated to a 28% reduction in wrinkle depth at week 24 in the monophasic filler-treated lesions, compared with a 20% decrease in the biphasic filler-treated folds. The week 48 improvement was 21% in the monophasic- and 17% in the biphasic-treated NLFs.

Self-rated patient satisfaction was scored on a 0-10 scale, with a lower score showing a higher level of satisfaction. From a baseline of 7.0, scores improved to 2.3 for the biphasic filler and 2.1 for the monophasic filler at week 2, to 4.9 for biphasic and 3.8 for monophasic at week 24, and to 6.7 for biphasic and 5.7 for monophasic at week 48.

Of note, the blinded patients consistently recorded significantly less injection site pain with the monophasic hyaluronic acid filler.

Belotero Intense is licensed in the United Kingdom and several European countries as a medical device for the correction of deep folds and for volume augmentation. A sister product, Belotero Balance, earned marketing approval from the Food and Drug Administration in November 2011 for correction of moderate to severe wrinkles and folds. Belotero Intense is intended for deeper injection and correction of more pronounced defects than is Belotero Balance.

Merz is seeking FDA approval of Belotero Intense.

The study presented by Dr. Kerscher was sponsored by Merz, which markets the Belotero product line. She is a consultant to the company.