Bruce Jancin

SAN ANTONIO — The sequence in which paclitaxel and anthracyclines are given for treatment of early breast cancer makes a big difference in long-term outcomes.

That’s the conclusion reached in what is believed to be the largest-ever retrospective study of the clinical impact of the sequencing of taxanes and anthracyclines. The study involved 3,010 early breast cancer patients who were treated during 1994-2009 and entered into the prospective online database at the University of Texas M.D. Anderson Cancer Center, Houston.

The clear winner was paclitaxel, followed by anthracycline-based therapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide, Dr. Ricardo H. Alvarez reported at the San Antonio Breast Cancer Symposium.

Starting with paclitaxel rather than an anthracycline-first regimen led to better long-term results in the settings of adjuvant chemotherapy and primary systemic (or neoadjuvant) therapy.

The adjuvant chemotherapy analysis included 1,596 women, three-quarters of whom received paclitaxel followed by anthracyclines. The 5-year relapse-free survival rate with this regimen was 88.8%, compared with 79.5% when anthracyclines were followed by paclitaxel. The 10-year relapse-free survival rates were 81.8% and 73.5%, respectively.

Five-year overall survival was 93.1% with paclitaxel followed by anthracyclines, compared with 83.2% for the reverse. The 10-year overall survival rates were 83.9% and 65.6%, respectively.

In a multivariate analysis that was stratified for potential confounders, including age, clinical stage, hormone receptor status, tumor grade, and era of diagnosis, the anthracyclines-first sequence was associated with a 67% increased risk of relapse (P less than .0001) and a 2.5-fold greater risk of mortality (P = .001), according to Dr. Alvarez, a medical oncologist at M.D. Anderson.

Among 1,414 patients who underwent neoadjuvant therapy, the 5-year relapse-free survival rate was 79.0% with the paclitaxel-first regimen vs. 61.2% with the anthracyclines-first regimen. Ten-year relapse-free survival occurred in 61.7% and 50.5%, respectively, of these patients.

Overall survival was 84.2% and 66.2% at 5 and 10 years, respectively, in patients who received paclitaxel followed by anthracyclines, compared with 71.3% and 53.4% in those who got anthracyclines first.

In a multivariate analysis, the anthracyclines-followed-by-paclitaxel sequence of neoadjuvant chemotherapy was associated with an adjusted 49% higher risk of relapse (P = .01) and a nonsignificant 28% increase in risk of all-cause mortality (P = .17), compared with the paclitaxel-first strategy.

The mechanism that accounts for the increased efficacy of taxane-first regimens for treatment of breast cancer is unclear, according to Dr. Alvarez.

He declared having no relevant financial relationships.

SAN ANTONIO — The sequence in which paclitaxel and anthracyclines are given for treatment of early breast cancer makes a big difference in long-term outcomes.

That’s the conclusion reached in what is believed to be the largest-ever retrospective study of the clinical impact of the sequencing of taxanes and anthracyclines. The study involved 3,010 early breast cancer patients who were treated during 1994-2009 and entered into the prospective online database at the University of Texas M.D. Anderson Cancer Center, Houston.

The clear winner was paclitaxel, followed by anthracycline-based therapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide, Dr. Ricardo H. Alvarez reported at the San Antonio Breast Cancer Symposium.

Starting with paclitaxel rather than an anthracycline-first regimen led to better long-term results in the settings of adjuvant chemotherapy and primary systemic (or neoadjuvant) therapy.

The adjuvant chemotherapy analysis included 1,596 women, three-quarters of whom received paclitaxel followed by anthracyclines. The 5-year relapse-free survival rate with this regimen was 88.8%, compared with 79.5% when anthracyclines were followed by paclitaxel. The 10-year relapse-free survival rates were 81.8% and 73.5%, respectively.

Five-year overall survival was 93.1% with paclitaxel followed by anthracyclines, compared with 83.2% for the reverse. The 10-year overall survival rates were 83.9% and 65.6%, respectively.

In a multivariate analysis that was stratified for potential confounders, including age, clinical stage, hormone receptor status, tumor grade, and era of diagnosis, the anthracyclines-first sequence was associated with a 67% increased risk of relapse (P less than .0001) and a 2.5-fold greater risk of mortality (P = .001), according to Dr. Alvarez, a medical oncologist at M.D. Anderson.

Among 1,414 patients who underwent neoadjuvant therapy, the 5-year relapse-free survival rate was 79.0% with the paclitaxel-first regimen vs. 61.2% with the anthracyclines-first regimen. Ten-year relapse-free survival occurred in 61.7% and 50.5%, respectively, of these patients.

Overall survival was 84.2% and 66.2% at 5 and 10 years, respectively, in patients who received paclitaxel followed by anthracyclines, compared with 71.3% and 53.4% in those who got anthracyclines first.

In a multivariate analysis, the anthracyclines-followed-by-paclitaxel sequence of neoadjuvant chemotherapy was associated with an adjusted 49% higher risk of relapse (P = .01) and a nonsignificant 28% increase in risk of all-cause mortality (P = .17), compared with the paclitaxel-first strategy.

The mechanism that accounts for the increased efficacy of taxane-first regimens for treatment of breast cancer is unclear, according to Dr. Alvarez.

He declared having no relevant financial relationships.

SAN ANTONIO — The sequence in which paclitaxel and anthracyclines are given for treatment of early breast cancer makes a big difference in long-term outcomes.

That’s the conclusion reached in what is believed to be the largest-ever retrospective study of the clinical impact of the sequencing of taxanes and anthracyclines. The study involved 3,010 early breast cancer patients who were treated during 1994-2009 and entered into the prospective online database at the University of Texas M.D. Anderson Cancer Center, Houston.

The clear winner was paclitaxel, followed by anthracycline-based therapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide, Dr. Ricardo H. Alvarez reported at the San Antonio Breast Cancer Symposium.

Starting with paclitaxel rather than an anthracycline-first regimen led to better long-term results in the settings of adjuvant chemotherapy and primary systemic (or neoadjuvant) therapy.

The adjuvant chemotherapy analysis included 1,596 women, three-quarters of whom received paclitaxel followed by anthracyclines. The 5-year relapse-free survival rate with this regimen was 88.8%, compared with 79.5% when anthracyclines were followed by paclitaxel. The 10-year relapse-free survival rates were 81.8% and 73.5%, respectively.

Five-year overall survival was 93.1% with paclitaxel followed by anthracyclines, compared with 83.2% for the reverse. The 10-year overall survival rates were 83.9% and 65.6%, respectively.

In a multivariate analysis that was stratified for potential confounders, including age, clinical stage, hormone receptor status, tumor grade, and era of diagnosis, the anthracyclines-first sequence was associated with a 67% increased risk of relapse (P less than .0001) and a 2.5-fold greater risk of mortality (P = .001), according to Dr. Alvarez, a medical oncologist at M.D. Anderson.

Among 1,414 patients who underwent neoadjuvant therapy, the 5-year relapse-free survival rate was 79.0% with the paclitaxel-first regimen vs. 61.2% with the anthracyclines-first regimen. Ten-year relapse-free survival occurred in 61.7% and 50.5%, respectively, of these patients.

Overall survival was 84.2% and 66.2% at 5 and 10 years, respectively, in patients who received paclitaxel followed by anthracyclines, compared with 71.3% and 53.4% in those who got anthracyclines first.

In a multivariate analysis, the anthracyclines-followed-by-paclitaxel sequence of neoadjuvant chemotherapy was associated with an adjusted 49% higher risk of relapse (P = .01) and a nonsignificant 28% increase in risk of all-cause mortality (P = .17), compared with the paclitaxel-first strategy.

The mechanism that accounts for the increased efficacy of taxane-first regimens for treatment of breast cancer is unclear, according to Dr. Alvarez.

He declared having no relevant financial relationships.

DENVER – Unintended pregnancies are threefold more frequent among unmarried sexually active female college students at 2-year as opposed to 4-year institutions.

Data from the Spring 2007 National College Health Assessment showed that, overall, 2.6% of unmarried sexually active female students aged 18-24 years at western U.S. colleges experienced an unwanted pregnancy during the past year. The rate was 5.3% among 1,433 attendees at 2-year colleges and 1.8% in 4,732 at 4-year schools, Lisa L. Lindley, Dr.PH, reported at the annual meeting of the American Public Health Association.

A multivariate logistic regression analysis identified nine risk factors associated with unintended pregnancy in young women attending 2-year institutions and 11 risk factors operative at 4-year schools. Some of these risk factors were common to both types of schools, while others were unique to one or the other.

Among the most striking shared risk factors was having been in a physically abusive relationship within the past year. This was associated with a 2.8-fold increased risk of unintended pregnancy at 2-year schools and a 4.5-fold elevated risk at 4-year colleges, according to Dr. Lindley of George Mason University, Fairfax, Va.

Use of the emergency contraceptive pill within the previous year was another risk factor for unintended pregnancy common to students at both types of colleges. It was associated with a 2.6-fold increased risk in unmarried sexually active students at 2-year schools and a 2.8-fold risk in those at 4-year schools.

Having a C or lower grade average was associated with a 2.2-fold increased likelihood of unintended pregnancy in women attending a 4-year college, but was not a significant risk factor at 2-year colleges. On the other hand, having unprotected sex in the past year as a consequence of drinking alcohol was a significant risk factor for unintended pregnancy at 2-year, but not 4-year institutions. Having had a gynecologic exam during the past year was associated with a 2.7-fold increased likelihood of unintended pregnancy among women at 2-year schools but wasn’t a significant factor at 4-year colleges.

Race was not a significant predictor of unintended pregnancy among the college students. This is an intriguing finding in light of the marked racial disparity in pregnancy rates among young women as a whole in the United States, Dr. Lindley said. For example, in 2004 the pregnancy rates among 20- to -24-year-old black and Hispanic women were 259 and 245 per 1,000 population, respectively, compared with 123 per 1,000 in similarly aged white women.

Dr. Lindley explained that the college study was undertaken in an effort to better understand the phenomenon of unintended pregnancy. Half of all pregnancies in the United States are unintended. Among young unmarried women this figure is far higher: 73% among 20- to 24-year-olds, and 86% in those under age 20.

Solid progress has been made in reducing the national pregnancy rate among 15- to 17-year-olds. But pregnancy rates among 18- to 24-year-olds remain excessive, she said.

A key lesson from the college study lies in the importance of addressing multiple risk factors at once for unwanted pregnancy, including abusive relationships – physical, emotional, and sexual –as well as alcohol use and proper use of the emergency contraceptive pill, Dr. Lindley added.

She said she had no relevant financial interests.

DENVER – Unintended pregnancies are threefold more frequent among unmarried sexually active female college students at 2-year as opposed to 4-year institutions.

Data from the Spring 2007 National College Health Assessment showed that, overall, 2.6% of unmarried sexually active female students aged 18-24 years at western U.S. colleges experienced an unwanted pregnancy during the past year. The rate was 5.3% among 1,433 attendees at 2-year colleges and 1.8% in 4,732 at 4-year schools, Lisa L. Lindley, Dr.PH, reported at the annual meeting of the American Public Health Association.

A multivariate logistic regression analysis identified nine risk factors associated with unintended pregnancy in young women attending 2-year institutions and 11 risk factors operative at 4-year schools. Some of these risk factors were common to both types of schools, while others were unique to one or the other.

Among the most striking shared risk factors was having been in a physically abusive relationship within the past year. This was associated with a 2.8-fold increased risk of unintended pregnancy at 2-year schools and a 4.5-fold elevated risk at 4-year colleges, according to Dr. Lindley of George Mason University, Fairfax, Va.

Use of the emergency contraceptive pill within the previous year was another risk factor for unintended pregnancy common to students at both types of colleges. It was associated with a 2.6-fold increased risk in unmarried sexually active students at 2-year schools and a 2.8-fold risk in those at 4-year schools.

Having a C or lower grade average was associated with a 2.2-fold increased likelihood of unintended pregnancy in women attending a 4-year college, but was not a significant risk factor at 2-year colleges. On the other hand, having unprotected sex in the past year as a consequence of drinking alcohol was a significant risk factor for unintended pregnancy at 2-year, but not 4-year institutions. Having had a gynecologic exam during the past year was associated with a 2.7-fold increased likelihood of unintended pregnancy among women at 2-year schools but wasn’t a significant factor at 4-year colleges.

Race was not a significant predictor of unintended pregnancy among the college students. This is an intriguing finding in light of the marked racial disparity in pregnancy rates among young women as a whole in the United States, Dr. Lindley said. For example, in 2004 the pregnancy rates among 20- to -24-year-old black and Hispanic women were 259 and 245 per 1,000 population, respectively, compared with 123 per 1,000 in similarly aged white women.

Dr. Lindley explained that the college study was undertaken in an effort to better understand the phenomenon of unintended pregnancy. Half of all pregnancies in the United States are unintended. Among young unmarried women this figure is far higher: 73% among 20- to 24-year-olds, and 86% in those under age 20.

Solid progress has been made in reducing the national pregnancy rate among 15- to 17-year-olds. But pregnancy rates among 18- to 24-year-olds remain excessive, she said.

A key lesson from the college study lies in the importance of addressing multiple risk factors at once for unwanted pregnancy, including abusive relationships – physical, emotional, and sexual –as well as alcohol use and proper use of the emergency contraceptive pill, Dr. Lindley added.

She said she had no relevant financial interests.

DENVER – Unintended pregnancies are threefold more frequent among unmarried sexually active female college students at 2-year as opposed to 4-year institutions.

Data from the Spring 2007 National College Health Assessment showed that, overall, 2.6% of unmarried sexually active female students aged 18-24 years at western U.S. colleges experienced an unwanted pregnancy during the past year. The rate was 5.3% among 1,433 attendees at 2-year colleges and 1.8% in 4,732 at 4-year schools, Lisa L. Lindley, Dr.PH, reported at the annual meeting of the American Public Health Association.

A multivariate logistic regression analysis identified nine risk factors associated with unintended pregnancy in young women attending 2-year institutions and 11 risk factors operative at 4-year schools. Some of these risk factors were common to both types of schools, while others were unique to one or the other.

Among the most striking shared risk factors was having been in a physically abusive relationship within the past year. This was associated with a 2.8-fold increased risk of unintended pregnancy at 2-year schools and a 4.5-fold elevated risk at 4-year colleges, according to Dr. Lindley of George Mason University, Fairfax, Va.

Use of the emergency contraceptive pill within the previous year was another risk factor for unintended pregnancy common to students at both types of colleges. It was associated with a 2.6-fold increased risk in unmarried sexually active students at 2-year schools and a 2.8-fold risk in those at 4-year schools.

Having a C or lower grade average was associated with a 2.2-fold increased likelihood of unintended pregnancy in women attending a 4-year college, but was not a significant risk factor at 2-year colleges. On the other hand, having unprotected sex in the past year as a consequence of drinking alcohol was a significant risk factor for unintended pregnancy at 2-year, but not 4-year institutions. Having had a gynecologic exam during the past year was associated with a 2.7-fold increased likelihood of unintended pregnancy among women at 2-year schools but wasn’t a significant factor at 4-year colleges.

Race was not a significant predictor of unintended pregnancy among the college students. This is an intriguing finding in light of the marked racial disparity in pregnancy rates among young women as a whole in the United States, Dr. Lindley said. For example, in 2004 the pregnancy rates among 20- to -24-year-old black and Hispanic women were 259 and 245 per 1,000 population, respectively, compared with 123 per 1,000 in similarly aged white women.

Dr. Lindley explained that the college study was undertaken in an effort to better understand the phenomenon of unintended pregnancy. Half of all pregnancies in the United States are unintended. Among young unmarried women this figure is far higher: 73% among 20- to 24-year-olds, and 86% in those under age 20.

Solid progress has been made in reducing the national pregnancy rate among 15- to 17-year-olds. But pregnancy rates among 18- to 24-year-olds remain excessive, she said.

A key lesson from the college study lies in the importance of addressing multiple risk factors at once for unwanted pregnancy, including abusive relationships – physical, emotional, and sexual –as well as alcohol use and proper use of the emergency contraceptive pill, Dr. Lindley added.

She said she had no relevant financial interests.

SAN ANTONIO – Women who form a seroma following breast cancer surgery are at threefold increased risk of developing lymphedema, a case-control study has shown.

Of 135 breast cancer survivors (26%) participating in the study, 35 developed postsurgical symptomatic seromas requiring needle aspiration. The seromas were located in the axilla, upper chest, and breast.

Of the 35 women with a seroma, 33 had a greater than 200-mL increase in arm volume. Based on the International Criteria for Lymphedema Diagnosis, 26 of the 35 women with a seroma had severe lymphedema, 6 had moderate lymphedema, and 3 had mild lymphedema symptoms, Mei R. Fu, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

Patients with a higher body mass index were significantly more likely to form a seroma; however, age, type of surgery performed, axillary lymph node status, and number of nodes removed proved unrelated to the occurrence of a seroma, according to Dr. Fu of the New York University College of Nursing.

Lymphedema is caused by accumulation of lymphatic fluid in interstitial spaces due to injury to the lymphatic system as a consequence of breast cancer therapy. Patients dread this common, distressing, long-term, and indeed often lifelong complication, she said.

Lymphedema is a syndrome with multiple symptoms. In this study, seroma formation – that is, excessive build-up of serous fluid – was associated with a markedly increased likelihood of the lymphedema-related symptoms of arm swelling, heaviness, numbness, stiffness, firmness, tenderness, and redness, as well as increased arm temperature. Patients with a seroma had a greater number of lymphedema-related symptoms than did women who developed lymphedema without a seroma.

A seroma is believed to form in response to surgical trauma and leakage of inflammatory exudates in the acute phase of wound healing. The excessive build-up of serous fluid leads to delayed wound healing, with tissue inflammation followed by fibrosis and necrosis.

Current standard management of a symptomatic seroma consists of needle aspiration, which may need to be done repeatedly. The clinical implication of this study is that aspiration of serous fluid isn’t sufficient to prevent lymphedema, Dr. Fu said. Further research is warranted on a novel means of preventing symptomatic seroma formation as a means of avoiding the development of lymphedema. Possibilities include the use of ultrasound for early detection and drainage of subclinical seromas, as well as potent anti-inflammatory therapy.

Her study was funded by the Avon Foundation and grants from other nonprofit organizations. She said she had no relevant financial disclosures.

SAN ANTONIO – Women who form a seroma following breast cancer surgery are at threefold increased risk of developing lymphedema, a case-control study has shown.

Of 135 breast cancer survivors (26%) participating in the study, 35 developed postsurgical symptomatic seromas requiring needle aspiration. The seromas were located in the axilla, upper chest, and breast.

Of the 35 women with a seroma, 33 had a greater than 200-mL increase in arm volume. Based on the International Criteria for Lymphedema Diagnosis, 26 of the 35 women with a seroma had severe lymphedema, 6 had moderate lymphedema, and 3 had mild lymphedema symptoms, Mei R. Fu, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

Patients with a higher body mass index were significantly more likely to form a seroma; however, age, type of surgery performed, axillary lymph node status, and number of nodes removed proved unrelated to the occurrence of a seroma, according to Dr. Fu of the New York University College of Nursing.

Lymphedema is caused by accumulation of lymphatic fluid in interstitial spaces due to injury to the lymphatic system as a consequence of breast cancer therapy. Patients dread this common, distressing, long-term, and indeed often lifelong complication, she said.

Lymphedema is a syndrome with multiple symptoms. In this study, seroma formation – that is, excessive build-up of serous fluid – was associated with a markedly increased likelihood of the lymphedema-related symptoms of arm swelling, heaviness, numbness, stiffness, firmness, tenderness, and redness, as well as increased arm temperature. Patients with a seroma had a greater number of lymphedema-related symptoms than did women who developed lymphedema without a seroma.

A seroma is believed to form in response to surgical trauma and leakage of inflammatory exudates in the acute phase of wound healing. The excessive build-up of serous fluid leads to delayed wound healing, with tissue inflammation followed by fibrosis and necrosis.

Current standard management of a symptomatic seroma consists of needle aspiration, which may need to be done repeatedly. The clinical implication of this study is that aspiration of serous fluid isn’t sufficient to prevent lymphedema, Dr. Fu said. Further research is warranted on a novel means of preventing symptomatic seroma formation as a means of avoiding the development of lymphedema. Possibilities include the use of ultrasound for early detection and drainage of subclinical seromas, as well as potent anti-inflammatory therapy.

Her study was funded by the Avon Foundation and grants from other nonprofit organizations. She said she had no relevant financial disclosures.

SAN ANTONIO – Women who form a seroma following breast cancer surgery are at threefold increased risk of developing lymphedema, a case-control study has shown.

Of 135 breast cancer survivors (26%) participating in the study, 35 developed postsurgical symptomatic seromas requiring needle aspiration. The seromas were located in the axilla, upper chest, and breast.

Of the 35 women with a seroma, 33 had a greater than 200-mL increase in arm volume. Based on the International Criteria for Lymphedema Diagnosis, 26 of the 35 women with a seroma had severe lymphedema, 6 had moderate lymphedema, and 3 had mild lymphedema symptoms, Mei R. Fu, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

Patients with a higher body mass index were significantly more likely to form a seroma; however, age, type of surgery performed, axillary lymph node status, and number of nodes removed proved unrelated to the occurrence of a seroma, according to Dr. Fu of the New York University College of Nursing.

Lymphedema is caused by accumulation of lymphatic fluid in interstitial spaces due to injury to the lymphatic system as a consequence of breast cancer therapy. Patients dread this common, distressing, long-term, and indeed often lifelong complication, she said.

Lymphedema is a syndrome with multiple symptoms. In this study, seroma formation – that is, excessive build-up of serous fluid – was associated with a markedly increased likelihood of the lymphedema-related symptoms of arm swelling, heaviness, numbness, stiffness, firmness, tenderness, and redness, as well as increased arm temperature. Patients with a seroma had a greater number of lymphedema-related symptoms than did women who developed lymphedema without a seroma.

A seroma is believed to form in response to surgical trauma and leakage of inflammatory exudates in the acute phase of wound healing. The excessive build-up of serous fluid leads to delayed wound healing, with tissue inflammation followed by fibrosis and necrosis.

Current standard management of a symptomatic seroma consists of needle aspiration, which may need to be done repeatedly. The clinical implication of this study is that aspiration of serous fluid isn’t sufficient to prevent lymphedema, Dr. Fu said. Further research is warranted on a novel means of preventing symptomatic seroma formation as a means of avoiding the development of lymphedema. Possibilities include the use of ultrasound for early detection and drainage of subclinical seromas, as well as potent anti-inflammatory therapy.

Her study was funded by the Avon Foundation and grants from other nonprofit organizations. She said she had no relevant financial disclosures.

SAN ANTONIO – Six cycles of adjuvant chemotherapy provided no added benefit over four in breast cancer patients with zero to three positive axillary lymph nodes in the Cancer and Leukemia Group B 40101 trial.

The 2-by-2 factorial design of CALGB 40101 aimed to address two key questions: the optimal duration of chemotherapy in patients with good-prognosis breast cancer, and the merits of paclitaxel- vs. anthracycline-based chemotherapy, long the backbone of adjuvant chemotherapy for breast cancer, Dr. Lawrence N. Shulman explained at the San Antonio Breast Cancer Symposium.

The data regarding the paclitaxel vs. doxorubicin-plus-cyclophosphamide comparison aren’t yet available for analysis, although the study’s data safety and monitoring board has indicated that the two regimens were equivalent. With regard to the optimal duration of adjuvant chemotherapy, however, the results are in – and longer is not better in this patient population, according to Dr. Shulman, chief medical officer and senior vice president for medical affairs at the Dana-Farber Cancer Institute in Boston.

The treatment-duration analysis involved 3,173 patients with operable breast cancer and zero to three positive axillary nodes. They were randomized first to either paclitaxel or doxorubicin/cyclophosphamide, and then further randomized to four or six cycles of their assigned chemotherapy. Most patients received the chemotherapy every 2 weeks.

With a median follow-up of 4.6 years, the relapse-free survival rate in patients who received six cycles of chemotherapy was 91.6% and closely similar at 91.8% in those who got four cycles. The overall survival rate was 95.3% in the six-cycle group, compared with 96.4% with four cycles, again a statistically similar outcome. Subset analyses showed no differential impact for chemotherapy duration based upon tumor estrogen receptor or HER2 status.

Grade 3/4 anemia, neutropenia, and fever were more frequent in the two anthracycline-based chemotherapy arms. Grade 3 neuropathy occurred only in the paclitaxel-treated patients, with rates of 6% in those who got four cycles and 13% with six. Grade 3-5 cardiac toxicity occurred in only 10 of the 3,173 patients, 7 of whom were in the anthracycline group.

Audience members hailed CALGB 40101 as an important study because it’s one of very few trials to examine duration of chemotherapy as a key variable.

Dr. Shulman said it’s possible that the six-cycle chemotherapy regimen will eventually pay off in terms of fewer distant metastases in this good-prognosis group of patients. Time will tell. But to date there have been 50 breast cancer–related deaths in the six-cycle treatment group and only 41 in those who got four cycles.

He declared having no relevant financial relationships.

SAN ANTONIO – Six cycles of adjuvant chemotherapy provided no added benefit over four in breast cancer patients with zero to three positive axillary lymph nodes in the Cancer and Leukemia Group B 40101 trial.

The 2-by-2 factorial design of CALGB 40101 aimed to address two key questions: the optimal duration of chemotherapy in patients with good-prognosis breast cancer, and the merits of paclitaxel- vs. anthracycline-based chemotherapy, long the backbone of adjuvant chemotherapy for breast cancer, Dr. Lawrence N. Shulman explained at the San Antonio Breast Cancer Symposium.

The data regarding the paclitaxel vs. doxorubicin-plus-cyclophosphamide comparison aren’t yet available for analysis, although the study’s data safety and monitoring board has indicated that the two regimens were equivalent. With regard to the optimal duration of adjuvant chemotherapy, however, the results are in – and longer is not better in this patient population, according to Dr. Shulman, chief medical officer and senior vice president for medical affairs at the Dana-Farber Cancer Institute in Boston.

The treatment-duration analysis involved 3,173 patients with operable breast cancer and zero to three positive axillary nodes. They were randomized first to either paclitaxel or doxorubicin/cyclophosphamide, and then further randomized to four or six cycles of their assigned chemotherapy. Most patients received the chemotherapy every 2 weeks.

With a median follow-up of 4.6 years, the relapse-free survival rate in patients who received six cycles of chemotherapy was 91.6% and closely similar at 91.8% in those who got four cycles. The overall survival rate was 95.3% in the six-cycle group, compared with 96.4% with four cycles, again a statistically similar outcome. Subset analyses showed no differential impact for chemotherapy duration based upon tumor estrogen receptor or HER2 status.

Grade 3/4 anemia, neutropenia, and fever were more frequent in the two anthracycline-based chemotherapy arms. Grade 3 neuropathy occurred only in the paclitaxel-treated patients, with rates of 6% in those who got four cycles and 13% with six. Grade 3-5 cardiac toxicity occurred in only 10 of the 3,173 patients, 7 of whom were in the anthracycline group.

Audience members hailed CALGB 40101 as an important study because it’s one of very few trials to examine duration of chemotherapy as a key variable.

Dr. Shulman said it’s possible that the six-cycle chemotherapy regimen will eventually pay off in terms of fewer distant metastases in this good-prognosis group of patients. Time will tell. But to date there have been 50 breast cancer–related deaths in the six-cycle treatment group and only 41 in those who got four cycles.

He declared having no relevant financial relationships.

SAN ANTONIO – Six cycles of adjuvant chemotherapy provided no added benefit over four in breast cancer patients with zero to three positive axillary lymph nodes in the Cancer and Leukemia Group B 40101 trial.

The 2-by-2 factorial design of CALGB 40101 aimed to address two key questions: the optimal duration of chemotherapy in patients with good-prognosis breast cancer, and the merits of paclitaxel- vs. anthracycline-based chemotherapy, long the backbone of adjuvant chemotherapy for breast cancer, Dr. Lawrence N. Shulman explained at the San Antonio Breast Cancer Symposium.

The data regarding the paclitaxel vs. doxorubicin-plus-cyclophosphamide comparison aren’t yet available for analysis, although the study’s data safety and monitoring board has indicated that the two regimens were equivalent. With regard to the optimal duration of adjuvant chemotherapy, however, the results are in – and longer is not better in this patient population, according to Dr. Shulman, chief medical officer and senior vice president for medical affairs at the Dana-Farber Cancer Institute in Boston.

The treatment-duration analysis involved 3,173 patients with operable breast cancer and zero to three positive axillary nodes. They were randomized first to either paclitaxel or doxorubicin/cyclophosphamide, and then further randomized to four or six cycles of their assigned chemotherapy. Most patients received the chemotherapy every 2 weeks.

With a median follow-up of 4.6 years, the relapse-free survival rate in patients who received six cycles of chemotherapy was 91.6% and closely similar at 91.8% in those who got four cycles. The overall survival rate was 95.3% in the six-cycle group, compared with 96.4% with four cycles, again a statistically similar outcome. Subset analyses showed no differential impact for chemotherapy duration based upon tumor estrogen receptor or HER2 status.

Grade 3/4 anemia, neutropenia, and fever were more frequent in the two anthracycline-based chemotherapy arms. Grade 3 neuropathy occurred only in the paclitaxel-treated patients, with rates of 6% in those who got four cycles and 13% with six. Grade 3-5 cardiac toxicity occurred in only 10 of the 3,173 patients, 7 of whom were in the anthracycline group.

Audience members hailed CALGB 40101 as an important study because it’s one of very few trials to examine duration of chemotherapy as a key variable.

Dr. Shulman said it’s possible that the six-cycle chemotherapy regimen will eventually pay off in terms of fewer distant metastases in this good-prognosis group of patients. Time will tell. But to date there have been 50 breast cancer–related deaths in the six-cycle treatment group and only 41 in those who got four cycles.

He declared having no relevant financial relationships.

DENVER — Elderly patients who consult their primary care physicians about depression or other mental health problems often get short shrift because of competing time demands in a busy office practice, an analysis of videotaped physician-patient encounters indicates.

Of 392 videotaped office visits involving elderly patients and primary care physicians in an academic medical center or solo practice, 59 addressed mental health issues, including 35 involving depression or suicidal thoughts. Surprisingly, one-third of the office visits in which elderly patients reported experiencing mental distress contain no discussion of psychotropic medications, SangNam Ahn, Ph.D., reported at the annual meeting of the American Public Health Association.

On average, 11% of the content of physician-patient encounters involving mental health issues was devoted to discussion of psychotropic medications. When prescribing these medications, primary care physicians presented more information about the drug’s purpose and brand name than about adverse effects, proper usage, or cost. Possible referral to a mental health professional was discussed in 12 of the 59 analyzed visits. A referral was actually made in seven cases, according to Dr. Ahn of the Texas A&M University, College Station.

Primary care physicians discussed an average of 7.4 distinct health issues per office visit with these elderly patients. Moreover, the patients had an average of two causes of disability limiting their activities. The thoroughness of discussion about psychotropic medications in this study was inversely related to the number of topics addressed: Patients with seven or eight health topics discussed during their office visit had 41% less discussion of psychotropic medication than did those with six or fewer topics discussed, and patients with nine or more topics addressed had 83% less discussion of psychotropic medication.

These study findings have several health policy implications. One is that busy primary care physicians should be encouraged to loosen time bottlenecks by liberal referral of elderly patients with mental disorders to mental health specialists. In addition, good-quality patient information leaflets should be developed for distribution by primary care physicians who prescribe psychotropic medications to elderly patients. And the reimbursement structure should be reformed by broadening reimbursement for telephone consultation and coordination of care, Dr. Ahn proposed.

Dr. Ahn declared having no relevant financial interests.

DENVER — Elderly patients who consult their primary care physicians about depression or other mental health problems often get short shrift because of competing time demands in a busy office practice, an analysis of videotaped physician-patient encounters indicates.

Of 392 videotaped office visits involving elderly patients and primary care physicians in an academic medical center or solo practice, 59 addressed mental health issues, including 35 involving depression or suicidal thoughts. Surprisingly, one-third of the office visits in which elderly patients reported experiencing mental distress contain no discussion of psychotropic medications, SangNam Ahn, Ph.D., reported at the annual meeting of the American Public Health Association.

On average, 11% of the content of physician-patient encounters involving mental health issues was devoted to discussion of psychotropic medications. When prescribing these medications, primary care physicians presented more information about the drug’s purpose and brand name than about adverse effects, proper usage, or cost. Possible referral to a mental health professional was discussed in 12 of the 59 analyzed visits. A referral was actually made in seven cases, according to Dr. Ahn of the Texas A&M University, College Station.

Primary care physicians discussed an average of 7.4 distinct health issues per office visit with these elderly patients. Moreover, the patients had an average of two causes of disability limiting their activities. The thoroughness of discussion about psychotropic medications in this study was inversely related to the number of topics addressed: Patients with seven or eight health topics discussed during their office visit had 41% less discussion of psychotropic medication than did those with six or fewer topics discussed, and patients with nine or more topics addressed had 83% less discussion of psychotropic medication.

These study findings have several health policy implications. One is that busy primary care physicians should be encouraged to loosen time bottlenecks by liberal referral of elderly patients with mental disorders to mental health specialists. In addition, good-quality patient information leaflets should be developed for distribution by primary care physicians who prescribe psychotropic medications to elderly patients. And the reimbursement structure should be reformed by broadening reimbursement for telephone consultation and coordination of care, Dr. Ahn proposed.

Dr. Ahn declared having no relevant financial interests.

DENVER — Elderly patients who consult their primary care physicians about depression or other mental health problems often get short shrift because of competing time demands in a busy office practice, an analysis of videotaped physician-patient encounters indicates.

Of 392 videotaped office visits involving elderly patients and primary care physicians in an academic medical center or solo practice, 59 addressed mental health issues, including 35 involving depression or suicidal thoughts. Surprisingly, one-third of the office visits in which elderly patients reported experiencing mental distress contain no discussion of psychotropic medications, SangNam Ahn, Ph.D., reported at the annual meeting of the American Public Health Association.

On average, 11% of the content of physician-patient encounters involving mental health issues was devoted to discussion of psychotropic medications. When prescribing these medications, primary care physicians presented more information about the drug’s purpose and brand name than about adverse effects, proper usage, or cost. Possible referral to a mental health professional was discussed in 12 of the 59 analyzed visits. A referral was actually made in seven cases, according to Dr. Ahn of the Texas A&M University, College Station.

Primary care physicians discussed an average of 7.4 distinct health issues per office visit with these elderly patients. Moreover, the patients had an average of two causes of disability limiting their activities. The thoroughness of discussion about psychotropic medications in this study was inversely related to the number of topics addressed: Patients with seven or eight health topics discussed during their office visit had 41% less discussion of psychotropic medication than did those with six or fewer topics discussed, and patients with nine or more topics addressed had 83% less discussion of psychotropic medication.

These study findings have several health policy implications. One is that busy primary care physicians should be encouraged to loosen time bottlenecks by liberal referral of elderly patients with mental disorders to mental health specialists. In addition, good-quality patient information leaflets should be developed for distribution by primary care physicians who prescribe psychotropic medications to elderly patients. And the reimbursement structure should be reformed by broadening reimbursement for telephone consultation and coordination of care, Dr. Ahn proposed.

Dr. Ahn declared having no relevant financial interests.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

SAN ANTONIO – Baseline obesity in breast cancer patients possessing the estrogen receptor–positive, HER2-negative disease subtype was independently associated with a 23% higher risk of recurrence and nearly a 50% increase in all-cause mortality compared with rates in the nonobese in a first-of-its-kind study.

“Our data suggest that obese patients with this breast cancer subtype are at increased risk of recurrence, and once that occurs there's a higher rate of progression of disease and a shorter time period between recurrence and death,” Dr. Joseph A. Sparano said at the annual San Antonio Breast Cancer Symposium.

The estrogen receptor–positive, HER2-negative form of breast cancer is the most common subtype, accounting for 50%-60% of all operable invasive breast cancers in the United States. It is generally viewed as having a more favorable prognosis than other subtypes, noted Dr. Sparano, professor of medicine and women's health at Albert Einstein College of Medicine and associate chairman of oncology at Montefiore Medical Center in Bronx, N.Y.

He presented a retrospective analysis of the Eastern Cooperative Oncology Group (ECOG) E1199 prospective randomized trial of various chemotherapy regimens, for which baseline body mass index data were available on 3,484 of the 5,168 participants. A total of 38% had a BMI of at least 30 kg/m

As expected based upon other studies, obesity was associated with older age, black race, and a higher rate of postmenopausal status.

In a Cox proportionate hazards model adjusted for these and other potential confounders including tumor size, surgery type, radiation therapy, and chemotherapy dosing and intensity, obese women with hormone receptor–positive, HER2-negative disease were 23% more likely to experience recurrence and had a 46% greater all-cause mortality than nonobese women with the same tumor subtype. In contrast, obesity had no impact on outcomes in women with the other two major breast cancer subtypes: triple-negative disease and HER2-positive breast cancer.

The investigators also examined the association between outcomes and BMI as a continuous rather than a categorical variable. After adjustment for potential confounders, they found that as baseline BMI increased in patients with estrogen receptor–positive, HER2-negative cancer, the risk of recurrence steadily increased in straightforward fashion. For mortality, on the other hand, there was an inflection point at about 30 kg/m

Other studies have documented inferior outcomes in breast cancer patients who are obese, but this is the first to break down the relationship according to disease subtype, said Dr. Sparano, who is chair of the ECOG breast committee.

He believes obesity may be a surrogate for other as yet unknown host-related factors that contribute to disease recurrence. One such factor might be hyperinsulinemia.

“Hyperinsulinemia is known to be associated with obesity, and estrogen receptor–positive disease in particular has been shown to more highly express the IGF [insulin-like growth factor] signaling pathway and the insulin receptor. So hyperinsulinemia may drive the growth of estrogen-dependent tumors – and hyperinsulinemia is potentially modifiable,” he noted.

Other hypothesized mechanisms include differences in treatment adherence or drug metabolism, he added.

Dr. Sparano declared that he has no financial conflicts of interest.

Obesity may be a surrogate for other as yet unknown host-related factors that contribute to recurrence.

Source DR. SPARANO

SAN ANTONIO – Baseline obesity in breast cancer patients possessing the estrogen receptor–positive, HER2-negative disease subtype was independently associated with a 23% higher risk of recurrence and nearly a 50% increase in all-cause mortality compared with rates in the nonobese in a first-of-its-kind study.

“Our data suggest that obese patients with this breast cancer subtype are at increased risk of recurrence, and once that occurs there's a higher rate of progression of disease and a shorter time period between recurrence and death,” Dr. Joseph A. Sparano said at the annual San Antonio Breast Cancer Symposium.

The estrogen receptor–positive, HER2-negative form of breast cancer is the most common subtype, accounting for 50%-60% of all operable invasive breast cancers in the United States. It is generally viewed as having a more favorable prognosis than other subtypes, noted Dr. Sparano, professor of medicine and women's health at Albert Einstein College of Medicine and associate chairman of oncology at Montefiore Medical Center in Bronx, N.Y.

He presented a retrospective analysis of the Eastern Cooperative Oncology Group (ECOG) E1199 prospective randomized trial of various chemotherapy regimens, for which baseline body mass index data were available on 3,484 of the 5,168 participants. A total of 38% had a BMI of at least 30 kg/m

As expected based upon other studies, obesity was associated with older age, black race, and a higher rate of postmenopausal status.

In a Cox proportionate hazards model adjusted for these and other potential confounders including tumor size, surgery type, radiation therapy, and chemotherapy dosing and intensity, obese women with hormone receptor–positive, HER2-negative disease were 23% more likely to experience recurrence and had a 46% greater all-cause mortality than nonobese women with the same tumor subtype. In contrast, obesity had no impact on outcomes in women with the other two major breast cancer subtypes: triple-negative disease and HER2-positive breast cancer.

The investigators also examined the association between outcomes and BMI as a continuous rather than a categorical variable. After adjustment for potential confounders, they found that as baseline BMI increased in patients with estrogen receptor–positive, HER2-negative cancer, the risk of recurrence steadily increased in straightforward fashion. For mortality, on the other hand, there was an inflection point at about 30 kg/m

Other studies have documented inferior outcomes in breast cancer patients who are obese, but this is the first to break down the relationship according to disease subtype, said Dr. Sparano, who is chair of the ECOG breast committee.

He believes obesity may be a surrogate for other as yet unknown host-related factors that contribute to disease recurrence. One such factor might be hyperinsulinemia.

“Hyperinsulinemia is known to be associated with obesity, and estrogen receptor–positive disease in particular has been shown to more highly express the IGF [insulin-like growth factor] signaling pathway and the insulin receptor. So hyperinsulinemia may drive the growth of estrogen-dependent tumors – and hyperinsulinemia is potentially modifiable,” he noted.

Other hypothesized mechanisms include differences in treatment adherence or drug metabolism, he added.

Dr. Sparano declared that he has no financial conflicts of interest.

Obesity may be a surrogate for other as yet unknown host-related factors that contribute to recurrence.

Source DR. SPARANO

SAN ANTONIO – Baseline obesity in breast cancer patients possessing the estrogen receptor–positive, HER2-negative disease subtype was independently associated with a 23% higher risk of recurrence and nearly a 50% increase in all-cause mortality compared with rates in the nonobese in a first-of-its-kind study.

“Our data suggest that obese patients with this breast cancer subtype are at increased risk of recurrence, and once that occurs there's a higher rate of progression of disease and a shorter time period between recurrence and death,” Dr. Joseph A. Sparano said at the annual San Antonio Breast Cancer Symposium.

The estrogen receptor–positive, HER2-negative form of breast cancer is the most common subtype, accounting for 50%-60% of all operable invasive breast cancers in the United States. It is generally viewed as having a more favorable prognosis than other subtypes, noted Dr. Sparano, professor of medicine and women's health at Albert Einstein College of Medicine and associate chairman of oncology at Montefiore Medical Center in Bronx, N.Y.

He presented a retrospective analysis of the Eastern Cooperative Oncology Group (ECOG) E1199 prospective randomized trial of various chemotherapy regimens, for which baseline body mass index data were available on 3,484 of the 5,168 participants. A total of 38% had a BMI of at least 30 kg/m

As expected based upon other studies, obesity was associated with older age, black race, and a higher rate of postmenopausal status.

In a Cox proportionate hazards model adjusted for these and other potential confounders including tumor size, surgery type, radiation therapy, and chemotherapy dosing and intensity, obese women with hormone receptor–positive, HER2-negative disease were 23% more likely to experience recurrence and had a 46% greater all-cause mortality than nonobese women with the same tumor subtype. In contrast, obesity had no impact on outcomes in women with the other two major breast cancer subtypes: triple-negative disease and HER2-positive breast cancer.

The investigators also examined the association between outcomes and BMI as a continuous rather than a categorical variable. After adjustment for potential confounders, they found that as baseline BMI increased in patients with estrogen receptor–positive, HER2-negative cancer, the risk of recurrence steadily increased in straightforward fashion. For mortality, on the other hand, there was an inflection point at about 30 kg/m

Other studies have documented inferior outcomes in breast cancer patients who are obese, but this is the first to break down the relationship according to disease subtype, said Dr. Sparano, who is chair of the ECOG breast committee.

He believes obesity may be a surrogate for other as yet unknown host-related factors that contribute to disease recurrence. One such factor might be hyperinsulinemia.

“Hyperinsulinemia is known to be associated with obesity, and estrogen receptor–positive disease in particular has been shown to more highly express the IGF [insulin-like growth factor] signaling pathway and the insulin receptor. So hyperinsulinemia may drive the growth of estrogen-dependent tumors – and hyperinsulinemia is potentially modifiable,” he noted.

Other hypothesized mechanisms include differences in treatment adherence or drug metabolism, he added.

Dr. Sparano declared that he has no financial conflicts of interest.

Obesity may be a surrogate for other as yet unknown host-related factors that contribute to recurrence.

Source DR. SPARANO

CHICAGO – Measurement of high-sensitivity C-reactive protein had little to no utility in refining cardiovascular risk assessment beyond that provided by the classic risk factors in a new secondary analysis of ASCOT, throwing into question the biomarker's appropriate role in clinical practice.

“In the ASCOT–Lipid Lowering Arm, neither baseline nor on-treatment CRP provided any useful information about the efficacy of statin treatment to reduce cardiovascular events beyond LDL cholesterol reduction. These results do not support current proposals to measure CRP in the clinical setting, either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment,” Dr. Peter S. Sever said at the meeting.

In ASCOT (the Anglo-Scandinavian Cardiac Outcomes Trial), combining a baseline determination of CRP with a standard Framingham Risk Score did not significantly enhance the ability to predict future cardiovascular disease events beyond that provided by Framingham score alone. And, while once patients were on statin therapy, the resultant reduction in LDL was associated with an impressive 55% reduction in cardiovascular events compared with placebo, the decrease in CRP was not linked to a significant decrease in such events, according to Dr. Sever, professor of clinical pharmacology and therapeutics at Imperial College, London.

ASCOT was a landmark primary prevention trial in which nearly 20,000 hypertensive patients were randomized to one of two antihypertensive regimens, then the 10,305 participants with a total cholesterol level of 250 mg/dL or less were re-randomized to 10 mg/day of atorvastatin (Lipitor) or placebo. Although this was a primary prevention trial, these were high-risk patients with three other cardiovascular risk factors in addition to hypertension and a mean 28% risk of developing cardiovascular disease within the next 10 years based upon their Framingham Risk Score.

The new retrospective ASCOT analysis involved 485 patients who experienced a coronary event or stroke during 3.3 years of follow-up and 1,367 controls who did not. Analyzing the data with use of four different statistical methods, neither baseline CRP nor change in CRP level after 6 months of statin therapy provided any practical information.

“I think our conclusion is fairly clear: In patients with hypertension, they're on statins. In patients with diabetes, they're on statins. In patients with stable coronary artery disease, they're on statins. There's no added benefit to be gained from measuring CRP,” Dr. Sever said.

Discussant Dr. Donald Lloyd-Jones said that “the ASCOT data are the latest adding to a large body of literature suggesting minimal clinical utility for CRP in risk assessment and decision making for lipid-lowering therapy, and a small, growing, and frankly mixed literature examining the utility of on-treatment CRP levels,” observed Dr. Lloyd-Jones, professor of preventive medicine at Northwestern University, Chicago.

In ASCOT, patients with an on-treatment LDL below the median had a reduced cardiovascular event risk regardless of their CRP level, while those with a higher LDL had a higher risk regardless of their CRP level. And among patients with a low on-treatment LDL, having a low CRP was not associated with additional benefit, he noted.

Factoring in baseline CRP resulted in a net reclassification improvement score, or NRI, of 0.005 in ASCOT participants at intermediate risk on the basis of their Framingham score. The NRI is a recently developed measure that has been embraced by preventive medicine because it expresses how useful a novel cardiovascular risk factor is in further defining Framingham intermediate-risk patients as either high- or low-risk. The NRI for baseline CRP in ASCOT was weak and nonsignificant. By contrast, the NRI for coronary artery calcium score in Framingham intermediate-risk patients in the Multi-Ethnic Study of Atherosclerosis (MESA) was a robust 0.55, more than two orders of magnitude greater than for CRP in ASCOT.

ASCOT is just the latest in a growing number of studies that raise a central question, he added: “Is CRP something we need to be spending our time on?”

So how often does Dr. Lloyd-Jones obtain a CRP in his own clinical practice? “Never,” he said in an interview.

Asked to comment, Dr. Christopher Cannon of Brigham and Women's Hospital, Boston, said his interpretation of the ASCOT results is that in patients who already have a good indication for statin therapy, knowing the baseline CRP level does not provide additional useful information.

“Once you get into places where you should be treating anyway, then CRP is not helpful. But in the JUPITER trial they had patients largely without other risk factors, and in that lower-risk group a high baseline CRP picked out those who would benefit from statin therapy,” Dr. Cannon explained.

He agreed with Dr. Sever and Dr. Lloyd-Jones that the message from ASCOT regarding the use of on-treatment CRP to titrate statin therapy is that it doesn't make sense.

Dr. Sever declared that he is a consultant to and is on the speakers bureau for Pfizer, which sponsored ASCOT. Dr. Cannon is also on the speakers bureau for Pfizer. Dr. Lloyd-Jones reported no relevant financial interests.

'In patients with diabetes, they're on statins. … There's no added benefit to be gained from measuring CRP.'

Source DR. SEVER

ASCOT is just the latest of several studies that ask, 'Is CRP something we need to be spending our time on?'

Source DR. LLOYD-JONES

CHICAGO – Measurement of high-sensitivity C-reactive protein had little to no utility in refining cardiovascular risk assessment beyond that provided by the classic risk factors in a new secondary analysis of ASCOT, throwing into question the biomarker's appropriate role in clinical practice.

“In the ASCOT–Lipid Lowering Arm, neither baseline nor on-treatment CRP provided any useful information about the efficacy of statin treatment to reduce cardiovascular events beyond LDL cholesterol reduction. These results do not support current proposals to measure CRP in the clinical setting, either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment,” Dr. Peter S. Sever said at the meeting.

In ASCOT (the Anglo-Scandinavian Cardiac Outcomes Trial), combining a baseline determination of CRP with a standard Framingham Risk Score did not significantly enhance the ability to predict future cardiovascular disease events beyond that provided by Framingham score alone. And, while once patients were on statin therapy, the resultant reduction in LDL was associated with an impressive 55% reduction in cardiovascular events compared with placebo, the decrease in CRP was not linked to a significant decrease in such events, according to Dr. Sever, professor of clinical pharmacology and therapeutics at Imperial College, London.

ASCOT was a landmark primary prevention trial in which nearly 20,000 hypertensive patients were randomized to one of two antihypertensive regimens, then the 10,305 participants with a total cholesterol level of 250 mg/dL or less were re-randomized to 10 mg/day of atorvastatin (Lipitor) or placebo. Although this was a primary prevention trial, these were high-risk patients with three other cardiovascular risk factors in addition to hypertension and a mean 28% risk of developing cardiovascular disease within the next 10 years based upon their Framingham Risk Score.

The new retrospective ASCOT analysis involved 485 patients who experienced a coronary event or stroke during 3.3 years of follow-up and 1,367 controls who did not. Analyzing the data with use of four different statistical methods, neither baseline CRP nor change in CRP level after 6 months of statin therapy provided any practical information.

“I think our conclusion is fairly clear: In patients with hypertension, they're on statins. In patients with diabetes, they're on statins. In patients with stable coronary artery disease, they're on statins. There's no added benefit to be gained from measuring CRP,” Dr. Sever said.

Discussant Dr. Donald Lloyd-Jones said that “the ASCOT data are the latest adding to a large body of literature suggesting minimal clinical utility for CRP in risk assessment and decision making for lipid-lowering therapy, and a small, growing, and frankly mixed literature examining the utility of on-treatment CRP levels,” observed Dr. Lloyd-Jones, professor of preventive medicine at Northwestern University, Chicago.

In ASCOT, patients with an on-treatment LDL below the median had a reduced cardiovascular event risk regardless of their CRP level, while those with a higher LDL had a higher risk regardless of their CRP level. And among patients with a low on-treatment LDL, having a low CRP was not associated with additional benefit, he noted.

Factoring in baseline CRP resulted in a net reclassification improvement score, or NRI, of 0.005 in ASCOT participants at intermediate risk on the basis of their Framingham score. The NRI is a recently developed measure that has been embraced by preventive medicine because it expresses how useful a novel cardiovascular risk factor is in further defining Framingham intermediate-risk patients as either high- or low-risk. The NRI for baseline CRP in ASCOT was weak and nonsignificant. By contrast, the NRI for coronary artery calcium score in Framingham intermediate-risk patients in the Multi-Ethnic Study of Atherosclerosis (MESA) was a robust 0.55, more than two orders of magnitude greater than for CRP in ASCOT.

ASCOT is just the latest in a growing number of studies that raise a central question, he added: “Is CRP something we need to be spending our time on?”

So how often does Dr. Lloyd-Jones obtain a CRP in his own clinical practice? “Never,” he said in an interview.

Asked to comment, Dr. Christopher Cannon of Brigham and Women's Hospital, Boston, said his interpretation of the ASCOT results is that in patients who already have a good indication for statin therapy, knowing the baseline CRP level does not provide additional useful information.

“Once you get into places where you should be treating anyway, then CRP is not helpful. But in the JUPITER trial they had patients largely without other risk factors, and in that lower-risk group a high baseline CRP picked out those who would benefit from statin therapy,” Dr. Cannon explained.

He agreed with Dr. Sever and Dr. Lloyd-Jones that the message from ASCOT regarding the use of on-treatment CRP to titrate statin therapy is that it doesn't make sense.

Dr. Sever declared that he is a consultant to and is on the speakers bureau for Pfizer, which sponsored ASCOT. Dr. Cannon is also on the speakers bureau for Pfizer. Dr. Lloyd-Jones reported no relevant financial interests.

'In patients with diabetes, they're on statins. … There's no added benefit to be gained from measuring CRP.'

Source DR. SEVER

ASCOT is just the latest of several studies that ask, 'Is CRP something we need to be spending our time on?'

Source DR. LLOYD-JONES

CHICAGO – Measurement of high-sensitivity C-reactive protein had little to no utility in refining cardiovascular risk assessment beyond that provided by the classic risk factors in a new secondary analysis of ASCOT, throwing into question the biomarker's appropriate role in clinical practice.

“In the ASCOT–Lipid Lowering Arm, neither baseline nor on-treatment CRP provided any useful information about the efficacy of statin treatment to reduce cardiovascular events beyond LDL cholesterol reduction. These results do not support current proposals to measure CRP in the clinical setting, either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment,” Dr. Peter S. Sever said at the meeting.

In ASCOT (the Anglo-Scandinavian Cardiac Outcomes Trial), combining a baseline determination of CRP with a standard Framingham Risk Score did not significantly enhance the ability to predict future cardiovascular disease events beyond that provided by Framingham score alone. And, while once patients were on statin therapy, the resultant reduction in LDL was associated with an impressive 55% reduction in cardiovascular events compared with placebo, the decrease in CRP was not linked to a significant decrease in such events, according to Dr. Sever, professor of clinical pharmacology and therapeutics at Imperial College, London.

ASCOT was a landmark primary prevention trial in which nearly 20,000 hypertensive patients were randomized to one of two antihypertensive regimens, then the 10,305 participants with a total cholesterol level of 250 mg/dL or less were re-randomized to 10 mg/day of atorvastatin (Lipitor) or placebo. Although this was a primary prevention trial, these were high-risk patients with three other cardiovascular risk factors in addition to hypertension and a mean 28% risk of developing cardiovascular disease within the next 10 years based upon their Framingham Risk Score.

The new retrospective ASCOT analysis involved 485 patients who experienced a coronary event or stroke during 3.3 years of follow-up and 1,367 controls who did not. Analyzing the data with use of four different statistical methods, neither baseline CRP nor change in CRP level after 6 months of statin therapy provided any practical information.

“I think our conclusion is fairly clear: In patients with hypertension, they're on statins. In patients with diabetes, they're on statins. In patients with stable coronary artery disease, they're on statins. There's no added benefit to be gained from measuring CRP,” Dr. Sever said.

Discussant Dr. Donald Lloyd-Jones said that “the ASCOT data are the latest adding to a large body of literature suggesting minimal clinical utility for CRP in risk assessment and decision making for lipid-lowering therapy, and a small, growing, and frankly mixed literature examining the utility of on-treatment CRP levels,” observed Dr. Lloyd-Jones, professor of preventive medicine at Northwestern University, Chicago.

In ASCOT, patients with an on-treatment LDL below the median had a reduced cardiovascular event risk regardless of their CRP level, while those with a higher LDL had a higher risk regardless of their CRP level. And among patients with a low on-treatment LDL, having a low CRP was not associated with additional benefit, he noted.

Factoring in baseline CRP resulted in a net reclassification improvement score, or NRI, of 0.005 in ASCOT participants at intermediate risk on the basis of their Framingham score. The NRI is a recently developed measure that has been embraced by preventive medicine because it expresses how useful a novel cardiovascular risk factor is in further defining Framingham intermediate-risk patients as either high- or low-risk. The NRI for baseline CRP in ASCOT was weak and nonsignificant. By contrast, the NRI for coronary artery calcium score in Framingham intermediate-risk patients in the Multi-Ethnic Study of Atherosclerosis (MESA) was a robust 0.55, more than two orders of magnitude greater than for CRP in ASCOT.

ASCOT is just the latest in a growing number of studies that raise a central question, he added: “Is CRP something we need to be spending our time on?”

So how often does Dr. Lloyd-Jones obtain a CRP in his own clinical practice? “Never,” he said in an interview.

Asked to comment, Dr. Christopher Cannon of Brigham and Women's Hospital, Boston, said his interpretation of the ASCOT results is that in patients who already have a good indication for statin therapy, knowing the baseline CRP level does not provide additional useful information.

“Once you get into places where you should be treating anyway, then CRP is not helpful. But in the JUPITER trial they had patients largely without other risk factors, and in that lower-risk group a high baseline CRP picked out those who would benefit from statin therapy,” Dr. Cannon explained.

He agreed with Dr. Sever and Dr. Lloyd-Jones that the message from ASCOT regarding the use of on-treatment CRP to titrate statin therapy is that it doesn't make sense.

Dr. Sever declared that he is a consultant to and is on the speakers bureau for Pfizer, which sponsored ASCOT. Dr. Cannon is also on the speakers bureau for Pfizer. Dr. Lloyd-Jones reported no relevant financial interests.

'In patients with diabetes, they're on statins. … There's no added benefit to be gained from measuring CRP.'

Source DR. SEVER

ASCOT is just the latest of several studies that ask, 'Is CRP something we need to be spending our time on?'

Source DR. LLOYD-JONES

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER