Doug Brunk

Major Finding: Identification of individualized tumor-specific rearrangements can be used to assess response to treatment and detect recurrence of solid lesions.

Data Source: Analysis of cancerous and normal tissue samples from four colorectal cancer patients and two breast cancer patients.

Disclosures: Under a licensing agreement between Johns Hopkins University and Genzyme, Dr. Velculescu and two of his coauthors are entitled to a share of royalties received by the university on sales of products related to the research.

SAN DIEGO — Scientists have developed a new way to track cancer using DNA-based blood tests to monitor individualized biomarkers after treatment of solid tumors, and thereby to detect cancer recurrence, an advance that could further the personalized management of cancer patients.

The method, known as PARE (Personalized Analysis of Rearranged Ends), “is based on next-generation mate-paired analysis of resected tumor DNA to identify individualized tumor-specific rearrangements,” Dr. Victor Velculescu and his coauthors said (Sci. Transl. Med. 2010 Feb. 24 [doi:10.1126/scitranslmed.3000702]). “Such alterations are used to develop [polymerase chain reaction]–based quantitative analyses for personalized tumor monitoring of plasma samples or other bodily fluids.”

During a press briefing at the annual meeting of the American Association for the Advancement of Science, one of the study's coauthors, Dr. Luis A. Diaz Jr., said that PARE “allows us to measure the amount of cancer DNA in any clinical specimen. As soon as a patient's cancer is identified by biopsy, it can be scanned for gene rearrangements. These rearrangements will then be a template to act as a fingerprint for that individual cancer. This can be applied in a variety of clinical scenarios.”

Dr. Velculescu, codirector of the cancer biology program at Johns Hopkins Kimmel Cancer Center in Baltimore, and his associates used six sets of tissue samples obtained from four patients with colorectal cancer and two patients with breast cancer to catalog the number of gene sequences in each patient. They did this by first identifying regions where the number of DNA sequences was more or less than anticipated and where sections of different chromosomes fused together.

The researchers analyzed these regions further to identify DNA sequences that displayed incorrect ordering, orientation, or spacing, and observed that an average of 9 rearrangements was found in each of the six samples (range, 4-17).

“The rearrangements represent the most dramatic form of genetic changes that can occur in the genome,” Dr. Velculescu said at the briefing. “If the genome were like a book with many chapters, the rearrangement would be like swapping of two chapters within book, so that both chapters would be out of order. If one could recognize rearrangements accurately, that could potentially be one of the best ways to distinguish cancer cells from normal cells.”

Next, they looked for the same changes as shed from tumors into the blood of patients. After amplifying DNA that was found in the blood of two of the colorectal cancer patients, they determined that the tests were robust enough to detect rearranged tumor DNA.

For example, the fraction of mutant DNA contained in the blood of one of the colorectal cancer patients was 37% prior to surgery for tumor removal, and it dropped to 14% after surgery. “The mutant DNA fraction decreased further after chemotherapy and subsequent removal of metastatic lesions from the right lobe of the liver,” the researchers reported. “However, the fraction of mutant tumor DNA did not reach zero (remaining at 0.3% at day 137), consistent with the fact that this patient had residual metastatic lesions in the remaining left lobe of the liver.”

The researchers noted certain limitations of the study, including the chance that some rearranged genetic sequences “could be lost during tumor progression,” and that the PARE assay currently costs about $5,000, making it expensive for general clinical use. “This cost is a consequence of the high physical coverage and the inefficiencies associated with stringent mapping of 25-bp sequence data to the human genome,” the researchers explained.

“As read quality and length continue to improve, less stringent mapping criteria and lower physical coverage will permit analyses similar to those in this study but with substantially less sequencing effort. Moreover, the cost of massively parallel sequencing, which has decreased substantially over the last 2 years, continues to spiral downwards.”

Despite such limitations, Dr. Velculescu and his associates maintain that the potential applications for PARE are “numerous,” including the identification of tumor-free surgical margins, the analysis of regional lymph nodes, and the measurement of circulating tumor DNA after surgery, radiation, or chemotherapy. “Short-term monitoring of circulating tumor DNA may be particularly useful in the testing of new drugs, as it could provide an earlier indication of efficacy than possible through conventional diagnostic methods such as computed tomography scanning,” they concluded.

At the briefing, Dr. Diaz, an oncologist at Johns Hopkins, said that PACE could be used to help clinicians determine who is cured or not cured after surgical resection. “Currently, as physicians we can't tell a patient after breast, colon, or lung cancer surgery whether or not they've been cured,” he commented. “A fraction of these patients will be cured by surgery alone, but many will have residual disease. We hope that PARE will be able to discriminate between those individuals that are cured and those that are not cured by detecting residual disease at first surgery. This approach would thereby spare cured individuals from unnecessary and potentially toxic and harmful chemotherapy.”

Major Finding: Identification of individualized tumor-specific rearrangements can be used to assess response to treatment and detect recurrence of solid lesions.

Data Source: Analysis of cancerous and normal tissue samples from four colorectal cancer patients and two breast cancer patients.

Disclosures: Under a licensing agreement between Johns Hopkins University and Genzyme, Dr. Velculescu and two of his coauthors are entitled to a share of royalties received by the university on sales of products related to the research.

SAN DIEGO — Scientists have developed a new way to track cancer using DNA-based blood tests to monitor individualized biomarkers after treatment of solid tumors, and thereby to detect cancer recurrence, an advance that could further the personalized management of cancer patients.

The method, known as PARE (Personalized Analysis of Rearranged Ends), “is based on next-generation mate-paired analysis of resected tumor DNA to identify individualized tumor-specific rearrangements,” Dr. Victor Velculescu and his coauthors said (Sci. Transl. Med. 2010 Feb. 24 [doi:10.1126/scitranslmed.3000702]). “Such alterations are used to develop [polymerase chain reaction]–based quantitative analyses for personalized tumor monitoring of plasma samples or other bodily fluids.”

During a press briefing at the annual meeting of the American Association for the Advancement of Science, one of the study's coauthors, Dr. Luis A. Diaz Jr., said that PARE “allows us to measure the amount of cancer DNA in any clinical specimen. As soon as a patient's cancer is identified by biopsy, it can be scanned for gene rearrangements. These rearrangements will then be a template to act as a fingerprint for that individual cancer. This can be applied in a variety of clinical scenarios.”

Dr. Velculescu, codirector of the cancer biology program at Johns Hopkins Kimmel Cancer Center in Baltimore, and his associates used six sets of tissue samples obtained from four patients with colorectal cancer and two patients with breast cancer to catalog the number of gene sequences in each patient. They did this by first identifying regions where the number of DNA sequences was more or less than anticipated and where sections of different chromosomes fused together.

The researchers analyzed these regions further to identify DNA sequences that displayed incorrect ordering, orientation, or spacing, and observed that an average of 9 rearrangements was found in each of the six samples (range, 4-17).

“The rearrangements represent the most dramatic form of genetic changes that can occur in the genome,” Dr. Velculescu said at the briefing. “If the genome were like a book with many chapters, the rearrangement would be like swapping of two chapters within book, so that both chapters would be out of order. If one could recognize rearrangements accurately, that could potentially be one of the best ways to distinguish cancer cells from normal cells.”

Next, they looked for the same changes as shed from tumors into the blood of patients. After amplifying DNA that was found in the blood of two of the colorectal cancer patients, they determined that the tests were robust enough to detect rearranged tumor DNA.

For example, the fraction of mutant DNA contained in the blood of one of the colorectal cancer patients was 37% prior to surgery for tumor removal, and it dropped to 14% after surgery. “The mutant DNA fraction decreased further after chemotherapy and subsequent removal of metastatic lesions from the right lobe of the liver,” the researchers reported. “However, the fraction of mutant tumor DNA did not reach zero (remaining at 0.3% at day 137), consistent with the fact that this patient had residual metastatic lesions in the remaining left lobe of the liver.”

The researchers noted certain limitations of the study, including the chance that some rearranged genetic sequences “could be lost during tumor progression,” and that the PARE assay currently costs about $5,000, making it expensive for general clinical use. “This cost is a consequence of the high physical coverage and the inefficiencies associated with stringent mapping of 25-bp sequence data to the human genome,” the researchers explained.

“As read quality and length continue to improve, less stringent mapping criteria and lower physical coverage will permit analyses similar to those in this study but with substantially less sequencing effort. Moreover, the cost of massively parallel sequencing, which has decreased substantially over the last 2 years, continues to spiral downwards.”

Despite such limitations, Dr. Velculescu and his associates maintain that the potential applications for PARE are “numerous,” including the identification of tumor-free surgical margins, the analysis of regional lymph nodes, and the measurement of circulating tumor DNA after surgery, radiation, or chemotherapy. “Short-term monitoring of circulating tumor DNA may be particularly useful in the testing of new drugs, as it could provide an earlier indication of efficacy than possible through conventional diagnostic methods such as computed tomography scanning,” they concluded.

At the briefing, Dr. Diaz, an oncologist at Johns Hopkins, said that PACE could be used to help clinicians determine who is cured or not cured after surgical resection. “Currently, as physicians we can't tell a patient after breast, colon, or lung cancer surgery whether or not they've been cured,” he commented. “A fraction of these patients will be cured by surgery alone, but many will have residual disease. We hope that PARE will be able to discriminate between those individuals that are cured and those that are not cured by detecting residual disease at first surgery. This approach would thereby spare cured individuals from unnecessary and potentially toxic and harmful chemotherapy.”

Major Finding: Identification of individualized tumor-specific rearrangements can be used to assess response to treatment and detect recurrence of solid lesions.

Data Source: Analysis of cancerous and normal tissue samples from four colorectal cancer patients and two breast cancer patients.

Disclosures: Under a licensing agreement between Johns Hopkins University and Genzyme, Dr. Velculescu and two of his coauthors are entitled to a share of royalties received by the university on sales of products related to the research.

SAN DIEGO — Scientists have developed a new way to track cancer using DNA-based blood tests to monitor individualized biomarkers after treatment of solid tumors, and thereby to detect cancer recurrence, an advance that could further the personalized management of cancer patients.

The method, known as PARE (Personalized Analysis of Rearranged Ends), “is based on next-generation mate-paired analysis of resected tumor DNA to identify individualized tumor-specific rearrangements,” Dr. Victor Velculescu and his coauthors said (Sci. Transl. Med. 2010 Feb. 24 [doi:10.1126/scitranslmed.3000702]). “Such alterations are used to develop [polymerase chain reaction]–based quantitative analyses for personalized tumor monitoring of plasma samples or other bodily fluids.”

During a press briefing at the annual meeting of the American Association for the Advancement of Science, one of the study's coauthors, Dr. Luis A. Diaz Jr., said that PARE “allows us to measure the amount of cancer DNA in any clinical specimen. As soon as a patient's cancer is identified by biopsy, it can be scanned for gene rearrangements. These rearrangements will then be a template to act as a fingerprint for that individual cancer. This can be applied in a variety of clinical scenarios.”

Dr. Velculescu, codirector of the cancer biology program at Johns Hopkins Kimmel Cancer Center in Baltimore, and his associates used six sets of tissue samples obtained from four patients with colorectal cancer and two patients with breast cancer to catalog the number of gene sequences in each patient. They did this by first identifying regions where the number of DNA sequences was more or less than anticipated and where sections of different chromosomes fused together.

The researchers analyzed these regions further to identify DNA sequences that displayed incorrect ordering, orientation, or spacing, and observed that an average of 9 rearrangements was found in each of the six samples (range, 4-17).

“The rearrangements represent the most dramatic form of genetic changes that can occur in the genome,” Dr. Velculescu said at the briefing. “If the genome were like a book with many chapters, the rearrangement would be like swapping of two chapters within book, so that both chapters would be out of order. If one could recognize rearrangements accurately, that could potentially be one of the best ways to distinguish cancer cells from normal cells.”

Next, they looked for the same changes as shed from tumors into the blood of patients. After amplifying DNA that was found in the blood of two of the colorectal cancer patients, they determined that the tests were robust enough to detect rearranged tumor DNA.

For example, the fraction of mutant DNA contained in the blood of one of the colorectal cancer patients was 37% prior to surgery for tumor removal, and it dropped to 14% after surgery. “The mutant DNA fraction decreased further after chemotherapy and subsequent removal of metastatic lesions from the right lobe of the liver,” the researchers reported. “However, the fraction of mutant tumor DNA did not reach zero (remaining at 0.3% at day 137), consistent with the fact that this patient had residual metastatic lesions in the remaining left lobe of the liver.”

The researchers noted certain limitations of the study, including the chance that some rearranged genetic sequences “could be lost during tumor progression,” and that the PARE assay currently costs about $5,000, making it expensive for general clinical use. “This cost is a consequence of the high physical coverage and the inefficiencies associated with stringent mapping of 25-bp sequence data to the human genome,” the researchers explained.

“As read quality and length continue to improve, less stringent mapping criteria and lower physical coverage will permit analyses similar to those in this study but with substantially less sequencing effort. Moreover, the cost of massively parallel sequencing, which has decreased substantially over the last 2 years, continues to spiral downwards.”

Despite such limitations, Dr. Velculescu and his associates maintain that the potential applications for PARE are “numerous,” including the identification of tumor-free surgical margins, the analysis of regional lymph nodes, and the measurement of circulating tumor DNA after surgery, radiation, or chemotherapy. “Short-term monitoring of circulating tumor DNA may be particularly useful in the testing of new drugs, as it could provide an earlier indication of efficacy than possible through conventional diagnostic methods such as computed tomography scanning,” they concluded.

At the briefing, Dr. Diaz, an oncologist at Johns Hopkins, said that PACE could be used to help clinicians determine who is cured or not cured after surgical resection. “Currently, as physicians we can't tell a patient after breast, colon, or lung cancer surgery whether or not they've been cured,” he commented. “A fraction of these patients will be cured by surgery alone, but many will have residual disease. We hope that PARE will be able to discriminate between those individuals that are cured and those that are not cured by detecting residual disease at first surgery. This approach would thereby spare cured individuals from unnecessary and potentially toxic and harmful chemotherapy.”

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 in those who used aspirin 1 day per week, 0.29 in those who used aspirin 2–5 days per week, and 0.36 in those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study, diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study showed.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” reported researchers led by Dr. Michelle D. Holmes of Harvard Medical School and Harvard School of Public Health, Boston.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [doi:10.1200/JCO.2009.22.7918]). The primary outcome measured was breast cancer mortality risk according to the number of days per week of aspirin use, categorized as 0, 1, 2–5, or 6–7 days.

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 in those who used aspirin 1 day per week, 0.29 in those who used aspirin 2–5 days per week, and 0.36 in those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study, diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study showed.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” reported researchers led by Dr. Michelle D. Holmes of Harvard Medical School and Harvard School of Public Health, Boston.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [doi:10.1200/JCO.2009.22.7918]). The primary outcome measured was breast cancer mortality risk according to the number of days per week of aspirin use, categorized as 0, 1, 2–5, or 6–7 days.

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 in those who used aspirin 1 day per week, 0.29 in those who used aspirin 2–5 days per week, and 0.36 in those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study, diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study showed.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” reported researchers led by Dr. Michelle D. Holmes of Harvard Medical School and Harvard School of Public Health, Boston.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [doi:10.1200/JCO.2009.22.7918]). The primary outcome measured was breast cancer mortality risk according to the number of days per week of aspirin use, categorized as 0, 1, 2–5, or 6–7 days.

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

SAN DIEGO — Patients with diabetic nephropathy have a slightly lower mean level of hemoglobin in the year leading up to the start of renal dialysis, compared with patients who have nondiabetic renal disease, results of a large analysis showed.

The difference persisted after adjustment for several other variables including age, gender, ethnicity, and estimated glomerular filtration rate, Dr. Daniel Ford said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford, of the United Kingdom Renal Registry, Bristol, England. “I suspect it's because patients with diabetic nephropathy have a higher incidence of concurrent diseases, which would make it more likely that they would suffer with more anemia than patients without diabetic renal diseases. However, we did not collect data on concurrent diseases, so we weren't able to adjust for that.”

Dr. Ford and his associates evaluated the records of 1,823 patients from the U.K. Renal Registry who underwent renal dialysis between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months before dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin.

The median age of patients was 66 years. Patients with diabetic nephropathy had slightly lower mean hemoglobin levels prior to undergoing dialysis, compared with those who had nondiabetic renal disease (10.8 vs. 11.0 g/dL, respectively). “It's a small difference, but it's statistically significant,” Dr. Ford said.

Disclosures: Dr. Ford had no relevant financial conflicts to disclose.

'It's a small difference, but it's statistically significant.'

Source Dr. Ford

SAN DIEGO — Patients with diabetic nephropathy have a slightly lower mean level of hemoglobin in the year leading up to the start of renal dialysis, compared with patients who have nondiabetic renal disease, results of a large analysis showed.

The difference persisted after adjustment for several other variables including age, gender, ethnicity, and estimated glomerular filtration rate, Dr. Daniel Ford said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford, of the United Kingdom Renal Registry, Bristol, England. “I suspect it's because patients with diabetic nephropathy have a higher incidence of concurrent diseases, which would make it more likely that they would suffer with more anemia than patients without diabetic renal diseases. However, we did not collect data on concurrent diseases, so we weren't able to adjust for that.”

Dr. Ford and his associates evaluated the records of 1,823 patients from the U.K. Renal Registry who underwent renal dialysis between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months before dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin.

The median age of patients was 66 years. Patients with diabetic nephropathy had slightly lower mean hemoglobin levels prior to undergoing dialysis, compared with those who had nondiabetic renal disease (10.8 vs. 11.0 g/dL, respectively). “It's a small difference, but it's statistically significant,” Dr. Ford said.

Disclosures: Dr. Ford had no relevant financial conflicts to disclose.

'It's a small difference, but it's statistically significant.'

Source Dr. Ford

SAN DIEGO — Patients with diabetic nephropathy have a slightly lower mean level of hemoglobin in the year leading up to the start of renal dialysis, compared with patients who have nondiabetic renal disease, results of a large analysis showed.

The difference persisted after adjustment for several other variables including age, gender, ethnicity, and estimated glomerular filtration rate, Dr. Daniel Ford said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford, of the United Kingdom Renal Registry, Bristol, England. “I suspect it's because patients with diabetic nephropathy have a higher incidence of concurrent diseases, which would make it more likely that they would suffer with more anemia than patients without diabetic renal diseases. However, we did not collect data on concurrent diseases, so we weren't able to adjust for that.”

Dr. Ford and his associates evaluated the records of 1,823 patients from the U.K. Renal Registry who underwent renal dialysis between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months before dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin.

The median age of patients was 66 years. Patients with diabetic nephropathy had slightly lower mean hemoglobin levels prior to undergoing dialysis, compared with those who had nondiabetic renal disease (10.8 vs. 11.0 g/dL, respectively). “It's a small difference, but it's statistically significant,” Dr. Ford said.

Disclosures: Dr. Ford had no relevant financial conflicts to disclose.

'It's a small difference, but it's statistically significant.'

Source Dr. Ford

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study who were diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study demonstrated.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” researchers led by Dr. Michelle D. Holmes of at Harvard Medical School and Harvard School of Public Health, Boston, reported in a study in the Journal of Clinical Oncology.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [10.1200/JCO.2009.22.7918

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study who were diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study demonstrated.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” researchers led by Dr. Michelle D. Holmes of at Harvard Medical School and Harvard School of Public Health, Boston, reported in a study in the Journal of Clinical Oncology.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [10.1200/JCO.2009.22.7918

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

Major Finding: Aspirin use after the diagnosis of stage I-III breast cancer was associated with a multivariate adjusted relative risk of breast cancer death of 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

Data Source: Responses from 4,164 female RNs in the Nurses' Health Study who were diagnosed with stage I-III breast cancer between 1976 and 2002. The women were observed until June 2006 or until they died, whichever came first.

Disclosures: Supported by a grant from the National Institutes of Health. The researchers indicated they had no potential conflicts of interest.

Aspirin use after the diagnosis of stage I-III breast cancer was associated with a decreased risk of breast cancer death and distant recurrence, results from the ongoing Nurses' Health Study demonstrated.

The study is believed to be the first to show a survival advantage among women with breast cancer who take aspirin.

“If confirmed, our results may broaden the scope of interventions available to reduce breast cancer–related death and mortality,” researchers led by Dr. Michelle D. Holmes of at Harvard Medical School and Harvard School of Public Health, Boston, reported in a study in the Journal of Clinical Oncology.

They emphasized that the results “may be generalizable only to longer term breast cancer survivors,” described as those who have lived long enough after diagnosis to report aspirin use after diagnosis (about 4 years).

The researchers used questionnaire data to evaluate aspirin use among 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002, and who were observed until they died or until June 2006, whichever came first (J. Clin. Oncol. 2010 Feb. 16 [10.1200/JCO.2009.22.7918

Dr. Holmes and her associates reported that 314 deaths attributed to breast cancer and 400 distant recurrences occurred during the study period. Compared with women who never used aspirin, the multivariate adjusted relative risk of breast cancer death was 1.07 among those who used aspirin 1 day per week, 0.29 for those who used aspirin 2–5 days per week, and 0.36 for those who used aspirin 6–7 days per week.

“Results did not differ appreciably when stratified by stage, [body mass index], menopausal status, or [estrogen receptor] status,” the researchers noted.

Aspirin use had a similar impact on distant recurrence of cancer. Compared with women who never used aspirin, the multivariate adjusted relative risk of distant recurrence was 0.91 among those who used aspirin 1 day per week, 0.40 for those who used aspirin 2–5 days per week, and 0.57 for those who used aspirin 6–7 days per week.

“We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death,” the researchers stated.

Dr. Lori Pierce, a member of the American Society of Clinical Oncology's Cancer Communications Committee, pointed out that although results from several studies suggest that aspirin may have beneficial effects against cancer because of its anti-inflammatory effects, “aspirin can cause stomach bleeding and is not for everyone. These are promising findings, and if they are confirmed in additional clinical trials, physicians may be able to regularly recommend aspirin to their breast cancer patients to reduce risk of cancer spread and mortality.”

Dr. Holmes and her associates acknowledged certain limitations of the study, including the fact that information on aspirin intake and distant recurrence was self-reported and that the study did not collect data on aspirin dosage.

Major Finding: Adding an ECG to a medical history and physical examination improved the overall sensitivity of preparticipation cardiovascular screening of college athletes to 90.9%, but also led to an increased rate of false-positive results.

Data Source: A single-center study of 510 athletes with a mean age of 19 years.

Disclosures: The researchers in the Baggish study had no funding resources to disclose. The Wheeler study was funded by the Stanford Cardiovascular Institute, the Breetwor Foundation, and a grant from the National Heart, Lung, and Blood Institute.

Adding electrocardiography to a medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening of college athletes, but is also associated with an increased rate of false-positive results, a single-center study demonstrated.

The analysis was undertaken because data that define the performance of screening practices in the United States “are sparse, and no studies have compared athlete screening by medical history and physical examination only with a strategy that includes ECG,” researchers led by Dr. Aaron L. Baggish, a cardiologist at Massachusetts General Hospital, Boston, reported.

The study population consisted of 510 athletes from Harvard University who underwent cardiovascular screening with a history and physical examination as well as an ECG between 2006 and 2008 (Ann. Intern. Med. 2010;152:269–75). Their mean age was 19 years and 61% were male.

Dr. Baggish and his associates used recommendations from the American College of Cardiology, the American Heart Association, and the National Collegiate Athletic Association to conduct the medical history and physical examination (Circulation 2007;115:1643–55). Current European Society of Cardiology criteria were used to screen for ECG abnormalities “because these are the only published recommendations designed for preparticipation screening,” the researchers explained.

Of the 510 study participants, 11 (2%) were found to have cardiac abnormalities relevant to sports participation. Ultimately, three were found to have an abnormality that met current recommendations for permanent or temporary sports restriction, including pulmonic valve stenosis, hypertrophic cardiomyopathy, and myocarditis. Screening with a medical history and physical exam alone detected abnormalities in 5 of the 11 athletes. This translated into a sensitivity of 45.5% and a specificity of 94.4%. It failed to catch the hypertrophic cardiomyopathy and myocarditis.

Adding an ECG helped the researchers detect an additional 5 athletes with abnormalities, for a total of 10 athletes. This improved the overall sensitivity of screening to 90.9%.

However, including ECG in the overall screening reduced the specificity of screening to 82.7% and was linked to a false-positive rate of 16.9%, which was significantly higher than the false-positive rate of 5.5% from screening with a medical history and physical exam alone.

“A screening program that falsely identifies approximately one in six participants as having cardiac disease has substantial and perhaps prohibitive financial, emotional, and logistical ramifications,” the researchers said. “However, screening strategies that minimize sensitivity have the greatest potential to minimize the incidence of sports-related sudden death.”

They went on to discuss certain limitations of the study, including the fact that “we cannot draw definitive conclusions about the effect of the different screening strategies on the incidence of sudden death in athletes” and the potential that some of the athletes “probably received screening before arriving at college,” which may “underrepresent the true burden of occult cardiac disease.”

But perhaps the greatest shortfall of the study, they said, is the ECG abnormality criteria used in the analysis, “which are accepted for widespread clinical use but were not derived from the study of athletes and therefore do not account for the numerous abnormal but benign ECG findings common in this population.”

In a separate study that appears in the same issue of the Annals of Internal Medicine, researchers led by Dr. Matthew T. Wheeler of the division of cardiovascular medicine at Stanford (Calif.) University used a decision analysis, cost-effectiveness model to evaluate the cost-effectiveness of an ECG plus a cardiovascular-focused history and physical examination, compared with a history and physical examination alone, for preparticipation screening of high school and college athletes aged 14–22 years (Ann. Intern. Med. 2010;152:276–86). The investigators drew from published epidemiologic and preparticipation screening data, vital statistics, and other data available to the public.

Dr. Wheeler and his associates found that adding an ECG to a history and physical examination saves 2.06 life-years for every 1,000 athletes screened at a total cost of $89 per athlete. This translated into a cost-effectiveness ratio of $42,900 per life-year saved, compared with a history and physical exam alone.

They also estimated that, compared with a strategy of no screening, an ECG plus a history and physical examination saves 2.6 life-years for every 1,000 athletes at a total cost of $199 per athlete. This translated into a cost-effectiveness ratio of $76,100 per life-year saved.

“Despite concerns about total cost, the incremental life-years saved by including ECG are significant,” the researchers concluded.

Major Finding: Adding an ECG to a medical history and physical examination improved the overall sensitivity of preparticipation cardiovascular screening of college athletes to 90.9%, but also led to an increased rate of false-positive results.

Data Source: A single-center study of 510 athletes with a mean age of 19 years.

Disclosures: The researchers in the Baggish study had no funding resources to disclose. The Wheeler study was funded by the Stanford Cardiovascular Institute, the Breetwor Foundation, and a grant from the National Heart, Lung, and Blood Institute.

Adding electrocardiography to a medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening of college athletes, but is also associated with an increased rate of false-positive results, a single-center study demonstrated.

The analysis was undertaken because data that define the performance of screening practices in the United States “are sparse, and no studies have compared athlete screening by medical history and physical examination only with a strategy that includes ECG,” researchers led by Dr. Aaron L. Baggish, a cardiologist at Massachusetts General Hospital, Boston, reported.

The study population consisted of 510 athletes from Harvard University who underwent cardiovascular screening with a history and physical examination as well as an ECG between 2006 and 2008 (Ann. Intern. Med. 2010;152:269–75). Their mean age was 19 years and 61% were male.

Dr. Baggish and his associates used recommendations from the American College of Cardiology, the American Heart Association, and the National Collegiate Athletic Association to conduct the medical history and physical examination (Circulation 2007;115:1643–55). Current European Society of Cardiology criteria were used to screen for ECG abnormalities “because these are the only published recommendations designed for preparticipation screening,” the researchers explained.

Of the 510 study participants, 11 (2%) were found to have cardiac abnormalities relevant to sports participation. Ultimately, three were found to have an abnormality that met current recommendations for permanent or temporary sports restriction, including pulmonic valve stenosis, hypertrophic cardiomyopathy, and myocarditis. Screening with a medical history and physical exam alone detected abnormalities in 5 of the 11 athletes. This translated into a sensitivity of 45.5% and a specificity of 94.4%. It failed to catch the hypertrophic cardiomyopathy and myocarditis.

Adding an ECG helped the researchers detect an additional 5 athletes with abnormalities, for a total of 10 athletes. This improved the overall sensitivity of screening to 90.9%.

However, including ECG in the overall screening reduced the specificity of screening to 82.7% and was linked to a false-positive rate of 16.9%, which was significantly higher than the false-positive rate of 5.5% from screening with a medical history and physical exam alone.

“A screening program that falsely identifies approximately one in six participants as having cardiac disease has substantial and perhaps prohibitive financial, emotional, and logistical ramifications,” the researchers said. “However, screening strategies that minimize sensitivity have the greatest potential to minimize the incidence of sports-related sudden death.”

They went on to discuss certain limitations of the study, including the fact that “we cannot draw definitive conclusions about the effect of the different screening strategies on the incidence of sudden death in athletes” and the potential that some of the athletes “probably received screening before arriving at college,” which may “underrepresent the true burden of occult cardiac disease.”

But perhaps the greatest shortfall of the study, they said, is the ECG abnormality criteria used in the analysis, “which are accepted for widespread clinical use but were not derived from the study of athletes and therefore do not account for the numerous abnormal but benign ECG findings common in this population.”

In a separate study that appears in the same issue of the Annals of Internal Medicine, researchers led by Dr. Matthew T. Wheeler of the division of cardiovascular medicine at Stanford (Calif.) University used a decision analysis, cost-effectiveness model to evaluate the cost-effectiveness of an ECG plus a cardiovascular-focused history and physical examination, compared with a history and physical examination alone, for preparticipation screening of high school and college athletes aged 14–22 years (Ann. Intern. Med. 2010;152:276–86). The investigators drew from published epidemiologic and preparticipation screening data, vital statistics, and other data available to the public.

Dr. Wheeler and his associates found that adding an ECG to a history and physical examination saves 2.06 life-years for every 1,000 athletes screened at a total cost of $89 per athlete. This translated into a cost-effectiveness ratio of $42,900 per life-year saved, compared with a history and physical exam alone.

They also estimated that, compared with a strategy of no screening, an ECG plus a history and physical examination saves 2.6 life-years for every 1,000 athletes at a total cost of $199 per athlete. This translated into a cost-effectiveness ratio of $76,100 per life-year saved.

“Despite concerns about total cost, the incremental life-years saved by including ECG are significant,” the researchers concluded.

Major Finding: Adding an ECG to a medical history and physical examination improved the overall sensitivity of preparticipation cardiovascular screening of college athletes to 90.9%, but also led to an increased rate of false-positive results.

Data Source: A single-center study of 510 athletes with a mean age of 19 years.

Disclosures: The researchers in the Baggish study had no funding resources to disclose. The Wheeler study was funded by the Stanford Cardiovascular Institute, the Breetwor Foundation, and a grant from the National Heart, Lung, and Blood Institute.

Adding electrocardiography to a medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening of college athletes, but is also associated with an increased rate of false-positive results, a single-center study demonstrated.

The analysis was undertaken because data that define the performance of screening practices in the United States “are sparse, and no studies have compared athlete screening by medical history and physical examination only with a strategy that includes ECG,” researchers led by Dr. Aaron L. Baggish, a cardiologist at Massachusetts General Hospital, Boston, reported.

The study population consisted of 510 athletes from Harvard University who underwent cardiovascular screening with a history and physical examination as well as an ECG between 2006 and 2008 (Ann. Intern. Med. 2010;152:269–75). Their mean age was 19 years and 61% were male.

Dr. Baggish and his associates used recommendations from the American College of Cardiology, the American Heart Association, and the National Collegiate Athletic Association to conduct the medical history and physical examination (Circulation 2007;115:1643–55). Current European Society of Cardiology criteria were used to screen for ECG abnormalities “because these are the only published recommendations designed for preparticipation screening,” the researchers explained.

Of the 510 study participants, 11 (2%) were found to have cardiac abnormalities relevant to sports participation. Ultimately, three were found to have an abnormality that met current recommendations for permanent or temporary sports restriction, including pulmonic valve stenosis, hypertrophic cardiomyopathy, and myocarditis. Screening with a medical history and physical exam alone detected abnormalities in 5 of the 11 athletes. This translated into a sensitivity of 45.5% and a specificity of 94.4%. It failed to catch the hypertrophic cardiomyopathy and myocarditis.

Adding an ECG helped the researchers detect an additional 5 athletes with abnormalities, for a total of 10 athletes. This improved the overall sensitivity of screening to 90.9%.

However, including ECG in the overall screening reduced the specificity of screening to 82.7% and was linked to a false-positive rate of 16.9%, which was significantly higher than the false-positive rate of 5.5% from screening with a medical history and physical exam alone.

“A screening program that falsely identifies approximately one in six participants as having cardiac disease has substantial and perhaps prohibitive financial, emotional, and logistical ramifications,” the researchers said. “However, screening strategies that minimize sensitivity have the greatest potential to minimize the incidence of sports-related sudden death.”

They went on to discuss certain limitations of the study, including the fact that “we cannot draw definitive conclusions about the effect of the different screening strategies on the incidence of sudden death in athletes” and the potential that some of the athletes “probably received screening before arriving at college,” which may “underrepresent the true burden of occult cardiac disease.”

But perhaps the greatest shortfall of the study, they said, is the ECG abnormality criteria used in the analysis, “which are accepted for widespread clinical use but were not derived from the study of athletes and therefore do not account for the numerous abnormal but benign ECG findings common in this population.”

In a separate study that appears in the same issue of the Annals of Internal Medicine, researchers led by Dr. Matthew T. Wheeler of the division of cardiovascular medicine at Stanford (Calif.) University used a decision analysis, cost-effectiveness model to evaluate the cost-effectiveness of an ECG plus a cardiovascular-focused history and physical examination, compared with a history and physical examination alone, for preparticipation screening of high school and college athletes aged 14–22 years (Ann. Intern. Med. 2010;152:276–86). The investigators drew from published epidemiologic and preparticipation screening data, vital statistics, and other data available to the public.

Dr. Wheeler and his associates found that adding an ECG to a history and physical examination saves 2.06 life-years for every 1,000 athletes screened at a total cost of $89 per athlete. This translated into a cost-effectiveness ratio of $42,900 per life-year saved, compared with a history and physical exam alone.

They also estimated that, compared with a strategy of no screening, an ECG plus a history and physical examination saves 2.6 life-years for every 1,000 athletes at a total cost of $199 per athlete. This translated into a cost-effectiveness ratio of $76,100 per life-year saved.

“Despite concerns about total cost, the incremental life-years saved by including ECG are significant,” the researchers concluded.

One of Dr. Mark Podwal's first memories of his interest in art dates back to early childhood in Brooklyn, N.Y., when a drawing that he sketched of a train caught the attention of his kindergarten teacher. Before that, he said, it seemed as if his teacher had not even noticed his name on the roster.

By the time he was a third-year medical student at New York University, the focus of his art had shifted from trains to far more serious subjects. It was 1968, and he sketched a collection of politically themed black-line drawings to protest the Vietnam War, including works on the killings of student protestors at Kent State University in Ohio and the bombing of Laos.

Martin Begun, who was associate dean of the medical school at the time, was so impressed by Dr. Podwal's surrealistic gouache paintings that he provided a space for him at Alumni Hall, the entrance to the medical school, to stage his first solo exhibition.

That event caught the eye of famed urologist Adrian Zorgniotti, who introduced Dr. Podwal to David Levine, the renowned political and literary caricaturist who drew for the New Yorker, New York Magazine, and the New York Review of Books.

“David was very encouraging,” recalled Dr. Podwal, a dermatologist who practices in New York City. Years later, he would be represented by Forum Gallery, which also represents Levine.

From that point on, Dr. Podwal's avocation as an artist began to skyrocket. He drew politically themed works for the op-ed pages of the New York Times and also created scores of Jewish-themed drawings and gouaches. The Metropolitan Museum of Art reproduced his art on 14 objects, including a Passover plate, jewelry, note cards, and prints. The Metropolitan Opera also commissioned him to create a series of Mozart portraits to sell as greeting cards.

Dr. Podwal has made his mark in other media as well, serving as executive producer and writer for the documentary “House of Life: The Old Jewish Cemetery in Prague,” narrated by Claire Bloom and broadcast nationwide on public television in the spring of 2009.

He also did illustrations for a book by Harold Bloom and four children's books by Francine Prose.

One of his most recent books, “Doctored Drawings” (Bellevue Literary Press, 2007), is a retrospective of his line drawings, mainly from works on medical subjects that appeared in the New York Times. One image from 1994, called “Mediscare,” portrays Congress as an octopus wielding a surgical instrument in each arm. “It's perfect for what Congress is doing to health care reform now,” Dr. Podwal said.

Another image from the book pokes fun at the circus of complexity surrounding the then-Clinton health plan. After the drawing first appeared in the New York Times, someone who worked in Dr. Podwal's office told him that she had fielded a telephone call at home from Rep. Henry Waxman (D-Calif.), whom she knew and “who was extremely upset with the drawing,” Dr. Podwal said. “If I can make a congressman upset by the drawing, I've achieved what I was trying to do.”

Dr. Podwal said that he is especially proud of the work he did on the “House of Life” film project. “I'm not religious, but I'm very emotionally attached to Judaism,” he said—so much so that every year, he and his family fly to Prague to mark Rosh Hashanah in the city's 700-year-old Old-New Synagogue.

“There's even a seat in the synagogue with my name on it,” he said.

He wrote and illustrated a children's book about the synagogue, called “Built by Angels” (Harcourt Children's Books, 2009). The Jewish Museum in Prague published the book in Czech with a forward by Dr. Podwal's friend, Nobel Peace Prize winner and Holocaust survivor Elie Wiesel.

“I've always had a talent for drawing, but I never thought I'd do anything with it,” he said. “I've achieved goals I never dreamed of.”

The amount of time that Dr. Podwal currently spends on his art and book projects is hard to quantify, he said, as his commissioned work is driven by deadlines.

And although he described dermatology as a visual specialty, he believes that is the only parallel between art and his medical specialty.

“Art gives a great opportunity to be creative and imaginative,” he said. “In medicine in America, if you're creative and imaginative, you're more likely to wind up in a malpractice suit, because you're not following the guidelines of your peers. Of course, there are creative and imaginative discoveries made, but as a practitioner, you tend not to be too creative and imaginative.”

This month, New York University will honor Dr. Podwal with its inaugural Alumni Award for Medicine in the Humanities.

What's next for the dermatologist who prefers painting and watercolors to line drawing?

Dr. Podwal said he is toying with the notion of illustrating the “Hebrew Melodies” poems of Lord Byron, as well as the Book of Ecclesiastes.

Dr. Podwal created “Matzoh Moon” (acrylic, gouache, and colored pencil on paper) in 2004.

Source ©2008 Dr. Mark Podwal, Courtesy Forum Gallery, New York

Irritating a congressman with one of his drawings was a great achievement, Dr. Mark Podwal said.

Source ©2007 Darryl Pitt

Dr. Podwal's “Mediscare” appeared in the New York Times in 1994, but “it's perfect for what Congress is doing to health care reform now,” he said.

Source Courtesy Dr. Mark Podwal

One of Dr. Mark Podwal's first memories of his interest in art dates back to early childhood in Brooklyn, N.Y., when a drawing that he sketched of a train caught the attention of his kindergarten teacher. Before that, he said, it seemed as if his teacher had not even noticed his name on the roster.

By the time he was a third-year medical student at New York University, the focus of his art had shifted from trains to far more serious subjects. It was 1968, and he sketched a collection of politically themed black-line drawings to protest the Vietnam War, including works on the killings of student protestors at Kent State University in Ohio and the bombing of Laos.

Martin Begun, who was associate dean of the medical school at the time, was so impressed by Dr. Podwal's surrealistic gouache paintings that he provided a space for him at Alumni Hall, the entrance to the medical school, to stage his first solo exhibition.

That event caught the eye of famed urologist Adrian Zorgniotti, who introduced Dr. Podwal to David Levine, the renowned political and literary caricaturist who drew for the New Yorker, New York Magazine, and the New York Review of Books.

“David was very encouraging,” recalled Dr. Podwal, a dermatologist who practices in New York City. Years later, he would be represented by Forum Gallery, which also represents Levine.

From that point on, Dr. Podwal's avocation as an artist began to skyrocket. He drew politically themed works for the op-ed pages of the New York Times and also created scores of Jewish-themed drawings and gouaches. The Metropolitan Museum of Art reproduced his art on 14 objects, including a Passover plate, jewelry, note cards, and prints. The Metropolitan Opera also commissioned him to create a series of Mozart portraits to sell as greeting cards.

Dr. Podwal has made his mark in other media as well, serving as executive producer and writer for the documentary “House of Life: The Old Jewish Cemetery in Prague,” narrated by Claire Bloom and broadcast nationwide on public television in the spring of 2009.

He also did illustrations for a book by Harold Bloom and four children's books by Francine Prose.

One of his most recent books, “Doctored Drawings” (Bellevue Literary Press, 2007), is a retrospective of his line drawings, mainly from works on medical subjects that appeared in the New York Times. One image from 1994, called “Mediscare,” portrays Congress as an octopus wielding a surgical instrument in each arm. “It's perfect for what Congress is doing to health care reform now,” Dr. Podwal said.

Another image from the book pokes fun at the circus of complexity surrounding the then-Clinton health plan. After the drawing first appeared in the New York Times, someone who worked in Dr. Podwal's office told him that she had fielded a telephone call at home from Rep. Henry Waxman (D-Calif.), whom she knew and “who was extremely upset with the drawing,” Dr. Podwal said. “If I can make a congressman upset by the drawing, I've achieved what I was trying to do.”

Dr. Podwal said that he is especially proud of the work he did on the “House of Life” film project. “I'm not religious, but I'm very emotionally attached to Judaism,” he said—so much so that every year, he and his family fly to Prague to mark Rosh Hashanah in the city's 700-year-old Old-New Synagogue.

“There's even a seat in the synagogue with my name on it,” he said.

He wrote and illustrated a children's book about the synagogue, called “Built by Angels” (Harcourt Children's Books, 2009). The Jewish Museum in Prague published the book in Czech with a forward by Dr. Podwal's friend, Nobel Peace Prize winner and Holocaust survivor Elie Wiesel.

“I've always had a talent for drawing, but I never thought I'd do anything with it,” he said. “I've achieved goals I never dreamed of.”

The amount of time that Dr. Podwal currently spends on his art and book projects is hard to quantify, he said, as his commissioned work is driven by deadlines.

And although he described dermatology as a visual specialty, he believes that is the only parallel between art and his medical specialty.

“Art gives a great opportunity to be creative and imaginative,” he said. “In medicine in America, if you're creative and imaginative, you're more likely to wind up in a malpractice suit, because you're not following the guidelines of your peers. Of course, there are creative and imaginative discoveries made, but as a practitioner, you tend not to be too creative and imaginative.”

This month, New York University will honor Dr. Podwal with its inaugural Alumni Award for Medicine in the Humanities.

What's next for the dermatologist who prefers painting and watercolors to line drawing?

Dr. Podwal said he is toying with the notion of illustrating the “Hebrew Melodies” poems of Lord Byron, as well as the Book of Ecclesiastes.

Dr. Podwal created “Matzoh Moon” (acrylic, gouache, and colored pencil on paper) in 2004.

Source ©2008 Dr. Mark Podwal, Courtesy Forum Gallery, New York

Irritating a congressman with one of his drawings was a great achievement, Dr. Mark Podwal said.

Source ©2007 Darryl Pitt

Dr. Podwal's “Mediscare” appeared in the New York Times in 1994, but “it's perfect for what Congress is doing to health care reform now,” he said.

Source Courtesy Dr. Mark Podwal

One of Dr. Mark Podwal's first memories of his interest in art dates back to early childhood in Brooklyn, N.Y., when a drawing that he sketched of a train caught the attention of his kindergarten teacher. Before that, he said, it seemed as if his teacher had not even noticed his name on the roster.

By the time he was a third-year medical student at New York University, the focus of his art had shifted from trains to far more serious subjects. It was 1968, and he sketched a collection of politically themed black-line drawings to protest the Vietnam War, including works on the killings of student protestors at Kent State University in Ohio and the bombing of Laos.

Martin Begun, who was associate dean of the medical school at the time, was so impressed by Dr. Podwal's surrealistic gouache paintings that he provided a space for him at Alumni Hall, the entrance to the medical school, to stage his first solo exhibition.

That event caught the eye of famed urologist Adrian Zorgniotti, who introduced Dr. Podwal to David Levine, the renowned political and literary caricaturist who drew for the New Yorker, New York Magazine, and the New York Review of Books.

“David was very encouraging,” recalled Dr. Podwal, a dermatologist who practices in New York City. Years later, he would be represented by Forum Gallery, which also represents Levine.

From that point on, Dr. Podwal's avocation as an artist began to skyrocket. He drew politically themed works for the op-ed pages of the New York Times and also created scores of Jewish-themed drawings and gouaches. The Metropolitan Museum of Art reproduced his art on 14 objects, including a Passover plate, jewelry, note cards, and prints. The Metropolitan Opera also commissioned him to create a series of Mozart portraits to sell as greeting cards.

Dr. Podwal has made his mark in other media as well, serving as executive producer and writer for the documentary “House of Life: The Old Jewish Cemetery in Prague,” narrated by Claire Bloom and broadcast nationwide on public television in the spring of 2009.

He also did illustrations for a book by Harold Bloom and four children's books by Francine Prose.

One of his most recent books, “Doctored Drawings” (Bellevue Literary Press, 2007), is a retrospective of his line drawings, mainly from works on medical subjects that appeared in the New York Times. One image from 1994, called “Mediscare,” portrays Congress as an octopus wielding a surgical instrument in each arm. “It's perfect for what Congress is doing to health care reform now,” Dr. Podwal said.

Another image from the book pokes fun at the circus of complexity surrounding the then-Clinton health plan. After the drawing first appeared in the New York Times, someone who worked in Dr. Podwal's office told him that she had fielded a telephone call at home from Rep. Henry Waxman (D-Calif.), whom she knew and “who was extremely upset with the drawing,” Dr. Podwal said. “If I can make a congressman upset by the drawing, I've achieved what I was trying to do.”

Dr. Podwal said that he is especially proud of the work he did on the “House of Life” film project. “I'm not religious, but I'm very emotionally attached to Judaism,” he said—so much so that every year, he and his family fly to Prague to mark Rosh Hashanah in the city's 700-year-old Old-New Synagogue.

“There's even a seat in the synagogue with my name on it,” he said.

He wrote and illustrated a children's book about the synagogue, called “Built by Angels” (Harcourt Children's Books, 2009). The Jewish Museum in Prague published the book in Czech with a forward by Dr. Podwal's friend, Nobel Peace Prize winner and Holocaust survivor Elie Wiesel.

“I've always had a talent for drawing, but I never thought I'd do anything with it,” he said. “I've achieved goals I never dreamed of.”

The amount of time that Dr. Podwal currently spends on his art and book projects is hard to quantify, he said, as his commissioned work is driven by deadlines.

And although he described dermatology as a visual specialty, he believes that is the only parallel between art and his medical specialty.

“Art gives a great opportunity to be creative and imaginative,” he said. “In medicine in America, if you're creative and imaginative, you're more likely to wind up in a malpractice suit, because you're not following the guidelines of your peers. Of course, there are creative and imaginative discoveries made, but as a practitioner, you tend not to be too creative and imaginative.”

This month, New York University will honor Dr. Podwal with its inaugural Alumni Award for Medicine in the Humanities.

What's next for the dermatologist who prefers painting and watercolors to line drawing?

Dr. Podwal said he is toying with the notion of illustrating the “Hebrew Melodies” poems of Lord Byron, as well as the Book of Ecclesiastes.

Dr. Podwal created “Matzoh Moon” (acrylic, gouache, and colored pencil on paper) in 2004.

Source ©2008 Dr. Mark Podwal, Courtesy Forum Gallery, New York

Irritating a congressman with one of his drawings was a great achievement, Dr. Mark Podwal said.

Source ©2007 Darryl Pitt

Dr. Podwal's “Mediscare” appeared in the New York Times in 1994, but “it's perfect for what Congress is doing to health care reform now,” he said.

Source Courtesy Dr. Mark Podwal

SAN DIEGO — Adults with type 2 diabetes and severe vitamin D deficiency face a twofold increased risk of all-cause mortality, independent of urinary albumin excretion rate and conventional cardiovascular risk factors, results from a long-term observational study showed.

Dr. Christel Joergensen, of the Steno Diabetes Center, Gentofte, Denmark, and her associates followed 290 white patients with type 2 diabetes for a median of 15.5 years. Severe vitamin D deficiency was defined as the lower 10th percentile (below 13.9 nmol/L), Dr. Joergensen, said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

At baseline, the mean age of patients was 54 years, 173 were normoalbuminuric, 73 had microalbuminuria, and 44 had macroalbuminuria. The median vitamin D level was 35.7 nmol/L, with a range of 5-137 nmol/L.

During follow-up, 142 patients (49%) died. Of these, 102 (73%) died from cardiovascular causes. All-cause mortality was significantly increased in patients with severe vitamin D deficiency (hazard ratio 2.3), an association that persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate, hemoglobin A_1c, and conventional cardiovascular risk factors (HR 1.94).

Severe vitamin D deficiency was also significantly associated with cardiovascular mortality (HR 1.93).

Dr. Joergensen acknowledged that the relatively small number of patients in the study was a limitation.

Disclosures: Dr. Joergensen had no financial conflicts of interest to disclose.

SAN DIEGO — Adults with type 2 diabetes and severe vitamin D deficiency face a twofold increased risk of all-cause mortality, independent of urinary albumin excretion rate and conventional cardiovascular risk factors, results from a long-term observational study showed.

Dr. Christel Joergensen, of the Steno Diabetes Center, Gentofte, Denmark, and her associates followed 290 white patients with type 2 diabetes for a median of 15.5 years. Severe vitamin D deficiency was defined as the lower 10th percentile (below 13.9 nmol/L), Dr. Joergensen, said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

At baseline, the mean age of patients was 54 years, 173 were normoalbuminuric, 73 had microalbuminuria, and 44 had macroalbuminuria. The median vitamin D level was 35.7 nmol/L, with a range of 5-137 nmol/L.

During follow-up, 142 patients (49%) died. Of these, 102 (73%) died from cardiovascular causes. All-cause mortality was significantly increased in patients with severe vitamin D deficiency (hazard ratio 2.3), an association that persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate, hemoglobin A_1c, and conventional cardiovascular risk factors (HR 1.94).

Severe vitamin D deficiency was also significantly associated with cardiovascular mortality (HR 1.93).

Dr. Joergensen acknowledged that the relatively small number of patients in the study was a limitation.

Disclosures: Dr. Joergensen had no financial conflicts of interest to disclose.

SAN DIEGO — Adults with type 2 diabetes and severe vitamin D deficiency face a twofold increased risk of all-cause mortality, independent of urinary albumin excretion rate and conventional cardiovascular risk factors, results from a long-term observational study showed.

Dr. Christel Joergensen, of the Steno Diabetes Center, Gentofte, Denmark, and her associates followed 290 white patients with type 2 diabetes for a median of 15.5 years. Severe vitamin D deficiency was defined as the lower 10th percentile (below 13.9 nmol/L), Dr. Joergensen, said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

At baseline, the mean age of patients was 54 years, 173 were normoalbuminuric, 73 had microalbuminuria, and 44 had macroalbuminuria. The median vitamin D level was 35.7 nmol/L, with a range of 5-137 nmol/L.

During follow-up, 142 patients (49%) died. Of these, 102 (73%) died from cardiovascular causes. All-cause mortality was significantly increased in patients with severe vitamin D deficiency (hazard ratio 2.3), an association that persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate, hemoglobin A_1c, and conventional cardiovascular risk factors (HR 1.94).

Severe vitamin D deficiency was also significantly associated with cardiovascular mortality (HR 1.93).

Dr. Joergensen acknowledged that the relatively small number of patients in the study was a limitation.

Disclosures: Dr. Joergensen had no financial conflicts of interest to disclose.

The FRAX tool to calculate the risk of major osteoporotic fracture and recommendations increasing vitamin D₃ intake are key components of the North American Menopause Society's updated position statement on the management of osteoporosis in postmenopausal women.

Last updated in 2006, the 2010 statement (www.menopause.org/aboutmeno/consensus.aspx

Among the new recommendations is the use of the World Health Organization's FRAX (Fracture Risk Assessment) tool to calculate a patient's 10-year risk of major osteoporotic fracture (hip, shoulder, wrist, and spine). Developed by researchers led by Dr. John A. Kanis of the University of Sheffield (England), FRAX is based on individual patient models that integrate the fracture risks associated with clinical risk factors as well as bone mineral density at the femoral neck. “People have been intimidated by the language associated with bone density reports over the years,” Dr. Steven T. Harris, a member of the editorial board that drafted the updated position statement, said in an interview. “It's distressing to be told that you have osteopenia or osteoporosis. To be able to use the FRAX tool to reduce that to a number—some reasonable estimate of fracture risk—is very helpful.”

Dr. Utian, a member of the 2008-2009 NAMS Board of Trustees who reviewed the position statement, said that FRAX was included because clinicians have come to realize “some of the limitations of DXA and the overuse of DXA, which could lead to inappropriate therapies. While DXA is a valuable tool, the FRAX gives you an ability to speak to individuals and actually give them an idea of what their risk is. It also gives health care organizations the ability to set parameters at what level of risk they would consider therapy to be indicated.”

According to the statement, drug therapy is indicated for postmenopausal women with osteoporotic vertebral or hip fracture; BMD values consistent with osteoporosis (a T score of −2.5 or lower); or a T score from −1.0 to −2.5 and a 10-year FRAX risk of major osteoporotic fracture (hip, shoulder, wrist, and spine) of at least 20% or hip fracture of at least 3%.

Another new part of the NAMS statement recommends that postmenopausal women obtain 800-1,000 IU/day of vitamin D₃, up from the recommended dosage of 400-600 IU/day contained in the 2006 statement. “There is more and more evidence that even in temperate areas, there isn't enough sun exposure to guarantee vitamin D sufficiency, particularly during the winter months,” said Dr. Harris of the University of California, San Francisco. “I think that the recommended allowance of 800-1,000 IU/day will be increased again at some point, but I think it's a reasonable starting point.”

As for choice of a specific osteoporosis therapy, the statement emphasizes that no head-to-head trials comparing the effectiveness of pharmacologic therapies to reduce fracture risk have been conducted. Current approved treatment options include bisphosphonates, selective estrogen-receptor modulators (SERMs), parathyroid hormone, estrogens, and calcitonin.

According to the statement, bisphosphonates “are the first-line drugs for treating postmenopausal women with osteoporosis. They have reduced the risk of vertebral fractures by 40%-70% and reduced the incidence of nonvertebral fracture, including hip fracture, by about half this amount.”

The SERM raloxifene “prevents bone loss and reduces the risk of vertebral fractures, but its effectiveness in reducing other fractures is uncertain. Extraskeletal risks and benefits are important when considering raloxifene therapy.”

Disclosures: The development of the statement was supported by an unrestricted educational grant from the Alliance for Better Bone Health, a collaboration between Warner Chilcott and its affiliates and Sanofi-Aventis US. Dr. Utian and Dr. Harris disclosed relationships with multiple pharmaceutical firms.

The FRAX tool to calculate the risk of major osteoporotic fracture and recommendations increasing vitamin D₃ intake are key components of the North American Menopause Society's updated position statement on the management of osteoporosis in postmenopausal women.

Last updated in 2006, the 2010 statement (www.menopause.org/aboutmeno/consensus.aspx

Among the new recommendations is the use of the World Health Organization's FRAX (Fracture Risk Assessment) tool to calculate a patient's 10-year risk of major osteoporotic fracture (hip, shoulder, wrist, and spine). Developed by researchers led by Dr. John A. Kanis of the University of Sheffield (England), FRAX is based on individual patient models that integrate the fracture risks associated with clinical risk factors as well as bone mineral density at the femoral neck. “People have been intimidated by the language associated with bone density reports over the years,” Dr. Steven T. Harris, a member of the editorial board that drafted the updated position statement, said in an interview. “It's distressing to be told that you have osteopenia or osteoporosis. To be able to use the FRAX tool to reduce that to a number—some reasonable estimate of fracture risk—is very helpful.”

Dr. Utian, a member of the 2008-2009 NAMS Board of Trustees who reviewed the position statement, said that FRAX was included because clinicians have come to realize “some of the limitations of DXA and the overuse of DXA, which could lead to inappropriate therapies. While DXA is a valuable tool, the FRAX gives you an ability to speak to individuals and actually give them an idea of what their risk is. It also gives health care organizations the ability to set parameters at what level of risk they would consider therapy to be indicated.”

According to the statement, drug therapy is indicated for postmenopausal women with osteoporotic vertebral or hip fracture; BMD values consistent with osteoporosis (a T score of −2.5 or lower); or a T score from −1.0 to −2.5 and a 10-year FRAX risk of major osteoporotic fracture (hip, shoulder, wrist, and spine) of at least 20% or hip fracture of at least 3%.

Another new part of the NAMS statement recommends that postmenopausal women obtain 800-1,000 IU/day of vitamin D₃, up from the recommended dosage of 400-600 IU/day contained in the 2006 statement. “There is more and more evidence that even in temperate areas, there isn't enough sun exposure to guarantee vitamin D sufficiency, particularly during the winter months,” said Dr. Harris of the University of California, San Francisco. “I think that the recommended allowance of 800-1,000 IU/day will be increased again at some point, but I think it's a reasonable starting point.”

As for choice of a specific osteoporosis therapy, the statement emphasizes that no head-to-head trials comparing the effectiveness of pharmacologic therapies to reduce fracture risk have been conducted. Current approved treatment options include bisphosphonates, selective estrogen-receptor modulators (SERMs), parathyroid hormone, estrogens, and calcitonin.

According to the statement, bisphosphonates “are the first-line drugs for treating postmenopausal women with osteoporosis. They have reduced the risk of vertebral fractures by 40%-70% and reduced the incidence of nonvertebral fracture, including hip fracture, by about half this amount.”

The SERM raloxifene “prevents bone loss and reduces the risk of vertebral fractures, but its effectiveness in reducing other fractures is uncertain. Extraskeletal risks and benefits are important when considering raloxifene therapy.”

Disclosures: The development of the statement was supported by an unrestricted educational grant from the Alliance for Better Bone Health, a collaboration between Warner Chilcott and its affiliates and Sanofi-Aventis US. Dr. Utian and Dr. Harris disclosed relationships with multiple pharmaceutical firms.

The FRAX tool to calculate the risk of major osteoporotic fracture and recommendations increasing vitamin D₃ intake are key components of the North American Menopause Society's updated position statement on the management of osteoporosis in postmenopausal women.

Last updated in 2006, the 2010 statement (www.menopause.org/aboutmeno/consensus.aspx

Among the new recommendations is the use of the World Health Organization's FRAX (Fracture Risk Assessment) tool to calculate a patient's 10-year risk of major osteoporotic fracture (hip, shoulder, wrist, and spine). Developed by researchers led by Dr. John A. Kanis of the University of Sheffield (England), FRAX is based on individual patient models that integrate the fracture risks associated with clinical risk factors as well as bone mineral density at the femoral neck. “People have been intimidated by the language associated with bone density reports over the years,” Dr. Steven T. Harris, a member of the editorial board that drafted the updated position statement, said in an interview. “It's distressing to be told that you have osteopenia or osteoporosis. To be able to use the FRAX tool to reduce that to a number—some reasonable estimate of fracture risk—is very helpful.”

Dr. Utian, a member of the 2008-2009 NAMS Board of Trustees who reviewed the position statement, said that FRAX was included because clinicians have come to realize “some of the limitations of DXA and the overuse of DXA, which could lead to inappropriate therapies. While DXA is a valuable tool, the FRAX gives you an ability to speak to individuals and actually give them an idea of what their risk is. It also gives health care organizations the ability to set parameters at what level of risk they would consider therapy to be indicated.”

According to the statement, drug therapy is indicated for postmenopausal women with osteoporotic vertebral or hip fracture; BMD values consistent with osteoporosis (a T score of −2.5 or lower); or a T score from −1.0 to −2.5 and a 10-year FRAX risk of major osteoporotic fracture (hip, shoulder, wrist, and spine) of at least 20% or hip fracture of at least 3%.

Another new part of the NAMS statement recommends that postmenopausal women obtain 800-1,000 IU/day of vitamin D₃, up from the recommended dosage of 400-600 IU/day contained in the 2006 statement. “There is more and more evidence that even in temperate areas, there isn't enough sun exposure to guarantee vitamin D sufficiency, particularly during the winter months,” said Dr. Harris of the University of California, San Francisco. “I think that the recommended allowance of 800-1,000 IU/day will be increased again at some point, but I think it's a reasonable starting point.”

As for choice of a specific osteoporosis therapy, the statement emphasizes that no head-to-head trials comparing the effectiveness of pharmacologic therapies to reduce fracture risk have been conducted. Current approved treatment options include bisphosphonates, selective estrogen-receptor modulators (SERMs), parathyroid hormone, estrogens, and calcitonin.

According to the statement, bisphosphonates “are the first-line drugs for treating postmenopausal women with osteoporosis. They have reduced the risk of vertebral fractures by 40%-70% and reduced the incidence of nonvertebral fracture, including hip fracture, by about half this amount.”

The SERM raloxifene “prevents bone loss and reduces the risk of vertebral fractures, but its effectiveness in reducing other fractures is uncertain. Extraskeletal risks and benefits are important when considering raloxifene therapy.”

Disclosures: The development of the statement was supported by an unrestricted educational grant from the Alliance for Better Bone Health, a collaboration between Warner Chilcott and its affiliates and Sanofi-Aventis US. Dr. Utian and Dr. Harris disclosed relationships with multiple pharmaceutical firms.

SAN DIEGO — The chances of a patient's developing multiple primary melanomas over a lifetime is a real phenomenon, with an incidence ranging from 2% to 8% among patients who have had a first melanoma, or an average of about 5%.

“That's significantly higher than if we apply the risk of melanoma to all fair-skinned people in the country,” Dr. William M. Burrows said at a melanoma update sponsored by the Scripps Clinic.

Of patients who develop more melanomas, about 80% develop two in addition to the original, 15% develop three, and the remainder develop more than three. “In my practice I have about four people I follow who have had five or six primary melanomas,” said Dr. Burrows, who has practiced dermatology for nearly 40 years and is currently with the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego.

He went on to note that the risk of multiple primary melanomas is twofold higher among men, and that the majority of subsequent primary melanomas (70%) occur on a different anatomical site, while 30% occur on the same site. “They have the same distribution as melanomas in general,” he said.

The majority of subsequent primary melanomas occur after 2 months, while 30% occur within 2 months or less.

Depth of invasion is similar to national statistics for all primary melanomas. “But the second primary melanoma tends to be thinner than the first one, which makes sense,” Dr. Burrows said. “After the first primary melanoma we raise our index of suspicion on lesions that are irregular. In addition, the patient has a significant level of worry.”

Recognized risk factors for multiple melanomas include presence of atypical/dysplastic nevi, family history, and early age of onset.

According to a review of 1,258 melanoma patients treated at the Scripps Clinic between 1990 and 2000, 149 (12%) developed multiple primary lesions, which is more than double the national incidence. “This could be due to one of two things,” Dr. Burrows said. “One is the criteria that are used in making the diagnosis of melanoma in situ. I wonder if we [at Scripps] diagnose melanoma in situ more often, as opposed to others who might sign it out as atypical melanocytic hyperplasia or another worrisome diagnosis.”

The other possibility is that incidence of melanoma is rising. “We know that we are making the diagnosis of primary melanomas at a younger age than we did 20 years ago,” Dr. Burrows said.

In the Scripps series, 75% of patients had two primary melanomas, 15% had three, and the remainder had four or more. The average age at initial primary melanoma diagnosis was 64 among men and 56 among women.

Nearly half of the patients (49%) developed subsequent melanomas less than 3 years after their initial primary melanoma diagnoses.

At this point, Dr. Burrows does not recommend testing for the CDKN2A and CDK4 gene mutations in most patients. “It's not a good screening tool for the general population or fair-skinned population with multiple nevi, but it has potential use in screening patients with a family history of melanoma,” he said.

As for managing patients with multiple melanomas, a full skin exam during initial work-up and follow-up intervals is essential, he said. “Follow-up should be lifelong.”

Dr. Burrows had no relevant conflicts to disclose.

'In my practice I have about four people I follow who have had five or six primary melanomas.'

Source DR. BURROWS

SAN DIEGO — The chances of a patient's developing multiple primary melanomas over a lifetime is a real phenomenon, with an incidence ranging from 2% to 8% among patients who have had a first melanoma, or an average of about 5%.

“That's significantly higher than if we apply the risk of melanoma to all fair-skinned people in the country,” Dr. William M. Burrows said at a melanoma update sponsored by the Scripps Clinic.

Of patients who develop more melanomas, about 80% develop two in addition to the original, 15% develop three, and the remainder develop more than three. “In my practice I have about four people I follow who have had five or six primary melanomas,” said Dr. Burrows, who has practiced dermatology for nearly 40 years and is currently with the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego.

He went on to note that the risk of multiple primary melanomas is twofold higher among men, and that the majority of subsequent primary melanomas (70%) occur on a different anatomical site, while 30% occur on the same site. “They have the same distribution as melanomas in general,” he said.

The majority of subsequent primary melanomas occur after 2 months, while 30% occur within 2 months or less.

Depth of invasion is similar to national statistics for all primary melanomas. “But the second primary melanoma tends to be thinner than the first one, which makes sense,” Dr. Burrows said. “After the first primary melanoma we raise our index of suspicion on lesions that are irregular. In addition, the patient has a significant level of worry.”

Recognized risk factors for multiple melanomas include presence of atypical/dysplastic nevi, family history, and early age of onset.

According to a review of 1,258 melanoma patients treated at the Scripps Clinic between 1990 and 2000, 149 (12%) developed multiple primary lesions, which is more than double the national incidence. “This could be due to one of two things,” Dr. Burrows said. “One is the criteria that are used in making the diagnosis of melanoma in situ. I wonder if we [at Scripps] diagnose melanoma in situ more often, as opposed to others who might sign it out as atypical melanocytic hyperplasia or another worrisome diagnosis.”

The other possibility is that incidence of melanoma is rising. “We know that we are making the diagnosis of primary melanomas at a younger age than we did 20 years ago,” Dr. Burrows said.

In the Scripps series, 75% of patients had two primary melanomas, 15% had three, and the remainder had four or more. The average age at initial primary melanoma diagnosis was 64 among men and 56 among women.

Nearly half of the patients (49%) developed subsequent melanomas less than 3 years after their initial primary melanoma diagnoses.

At this point, Dr. Burrows does not recommend testing for the CDKN2A and CDK4 gene mutations in most patients. “It's not a good screening tool for the general population or fair-skinned population with multiple nevi, but it has potential use in screening patients with a family history of melanoma,” he said.

As for managing patients with multiple melanomas, a full skin exam during initial work-up and follow-up intervals is essential, he said. “Follow-up should be lifelong.”

Dr. Burrows had no relevant conflicts to disclose.

'In my practice I have about four people I follow who have had five or six primary melanomas.'

Source DR. BURROWS

SAN DIEGO — The chances of a patient's developing multiple primary melanomas over a lifetime is a real phenomenon, with an incidence ranging from 2% to 8% among patients who have had a first melanoma, or an average of about 5%.

“That's significantly higher than if we apply the risk of melanoma to all fair-skinned people in the country,” Dr. William M. Burrows said at a melanoma update sponsored by the Scripps Clinic.

Of patients who develop more melanomas, about 80% develop two in addition to the original, 15% develop three, and the remainder develop more than three. “In my practice I have about four people I follow who have had five or six primary melanomas,” said Dr. Burrows, who has practiced dermatology for nearly 40 years and is currently with the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego.

He went on to note that the risk of multiple primary melanomas is twofold higher among men, and that the majority of subsequent primary melanomas (70%) occur on a different anatomical site, while 30% occur on the same site. “They have the same distribution as melanomas in general,” he said.

The majority of subsequent primary melanomas occur after 2 months, while 30% occur within 2 months or less.

Depth of invasion is similar to national statistics for all primary melanomas. “But the second primary melanoma tends to be thinner than the first one, which makes sense,” Dr. Burrows said. “After the first primary melanoma we raise our index of suspicion on lesions that are irregular. In addition, the patient has a significant level of worry.”

Recognized risk factors for multiple melanomas include presence of atypical/dysplastic nevi, family history, and early age of onset.

According to a review of 1,258 melanoma patients treated at the Scripps Clinic between 1990 and 2000, 149 (12%) developed multiple primary lesions, which is more than double the national incidence. “This could be due to one of two things,” Dr. Burrows said. “One is the criteria that are used in making the diagnosis of melanoma in situ. I wonder if we [at Scripps] diagnose melanoma in situ more often, as opposed to others who might sign it out as atypical melanocytic hyperplasia or another worrisome diagnosis.”

The other possibility is that incidence of melanoma is rising. “We know that we are making the diagnosis of primary melanomas at a younger age than we did 20 years ago,” Dr. Burrows said.

In the Scripps series, 75% of patients had two primary melanomas, 15% had three, and the remainder had four or more. The average age at initial primary melanoma diagnosis was 64 among men and 56 among women.

Nearly half of the patients (49%) developed subsequent melanomas less than 3 years after their initial primary melanoma diagnoses.

At this point, Dr. Burrows does not recommend testing for the CDKN2A and CDK4 gene mutations in most patients. “It's not a good screening tool for the general population or fair-skinned population with multiple nevi, but it has potential use in screening patients with a family history of melanoma,” he said.

As for managing patients with multiple melanomas, a full skin exam during initial work-up and follow-up intervals is essential, he said. “Follow-up should be lifelong.”

Dr. Burrows had no relevant conflicts to disclose.

'In my practice I have about four people I follow who have had five or six primary melanomas.'

Source DR. BURROWS

LAS VEGAS — Even though acitretin is labeled as a pregnancy category X drug, Dr. Craig L. Leonardi claimed he sees at least one patient of childbearing potential per month who is referred to him on the agent.

“I think that's a terrifically bad practice,” said Dr. Leonardi at a dermatology seminar sponsored by Skin Disease Education Foundation. “You need to think this one through.”

The chief risk posed by use of the drug in women of childbearing potential is retinoid embryopathy, which occurs in 33% of preterm infants exposed to the drug in utero. “As a consequence this drug should not be used in females of childbearing potential, which takes the drug off the list for half the population of our younger psoriasis patients,” said Dr. Leonardi, clinical professor of dermatology at St. Louis University. “Since there is no teratogenic threshold established for any of the oral synthetic retinoids, this drug just shouldn't be used in females of childbearing potential.”

The recommended acitretin pregnancy avoidance period is 3 years in the United States and 2 years in Europe.

Another downside of the drug is that it converts to detectable levels of etretinate in the presence of alcohol ingestion (based on consumption of 8 ounces by a patient weighing at least 75 kg).

A second-generation retinoid, acitretin (Soriatane, Stiefel Laboratories) is available in 10-g and 25-g gel caps. Common doses in psoriasis treatment are 25 mg twice daily, 25 mg twice daily for 1 month followed by 25 mg once daily, or starting off at 25 mg once daily.

Dr. Leonardi said he rarely prescribes acitretin as monotherapy for psoriasis because it has a modest effect on the disease, compared with cyclosporin and methotrexate, resulting in about a 50% reduction of body surface area over a period of 8-24 weeks. In addition, acitretin was approved for psoriasis based on trials involving only 275 patients, and “interpretation of the trial data is difficult,” he said. “If this were a biologic drug it would be shelved.”

Adverse events that occur in more than 20% of patients taking 50 mg/day over 8 weeks include chelitis, skin peeling, pruritus, rhinitis, dry skin, and alopecia. “It's a little bit less of an issue if you use the smaller dose, but nonetheless, these are significant numbers,” Dr. Leonardi said. “There are some significant, common adverse events while on this therapy.”

Despite its modest effect as monotherapy, acitretin “has a very unique mechanism of action,” he noted. “It decreases hyperproliferation of keratinocytes, it decreases inflammation directly, and it helps to normalize differentiation of the skin.”

He went on to point out that acitretin is most effective when combined with other treatments, particularly psoralen and ultraviolet light radiation (PUVA). One study of this combination demonstrated 89% clearance of psoriatic lesions at 8 weeks and 94% clearance at 12 weeks (Dertmatologica 1988;177:218-24).

A more recent trial evaluated the impact of 25 mg/day acitretin plus narrow band ultraviolet B light three times a week in 40 difficult-to-treat psoriasis patients (J. Dermatolog. Treat. 2003;14[suppl 2]:17-20). It found that 88% of patients had at least a moderate improvement of psoriasis and 73% had an improvement of at least 75%.

Dr. Leonardi disclosed he is a consultant, investigator, and member of the speakers bureau for several pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

An interview with Dr. Leonardi can be viewed by visiting www.youtube.com/user/FamilyPracticeNews#p/u/8/XA5NCq4fihQ

'There is no teratogenic threshold established for any of the oral synthetic retinoids.'

Source DR. LEONARDI

LAS VEGAS — Even though acitretin is labeled as a pregnancy category X drug, Dr. Craig L. Leonardi claimed he sees at least one patient of childbearing potential per month who is referred to him on the agent.

“I think that's a terrifically bad practice,” said Dr. Leonardi at a dermatology seminar sponsored by Skin Disease Education Foundation. “You need to think this one through.”

The chief risk posed by use of the drug in women of childbearing potential is retinoid embryopathy, which occurs in 33% of preterm infants exposed to the drug in utero. “As a consequence this drug should not be used in females of childbearing potential, which takes the drug off the list for half the population of our younger psoriasis patients,” said Dr. Leonardi, clinical professor of dermatology at St. Louis University. “Since there is no teratogenic threshold established for any of the oral synthetic retinoids, this drug just shouldn't be used in females of childbearing potential.”

The recommended acitretin pregnancy avoidance period is 3 years in the United States and 2 years in Europe.

Another downside of the drug is that it converts to detectable levels of etretinate in the presence of alcohol ingestion (based on consumption of 8 ounces by a patient weighing at least 75 kg).

A second-generation retinoid, acitretin (Soriatane, Stiefel Laboratories) is available in 10-g and 25-g gel caps. Common doses in psoriasis treatment are 25 mg twice daily, 25 mg twice daily for 1 month followed by 25 mg once daily, or starting off at 25 mg once daily.

Dr. Leonardi said he rarely prescribes acitretin as monotherapy for psoriasis because it has a modest effect on the disease, compared with cyclosporin and methotrexate, resulting in about a 50% reduction of body surface area over a period of 8-24 weeks. In addition, acitretin was approved for psoriasis based on trials involving only 275 patients, and “interpretation of the trial data is difficult,” he said. “If this were a biologic drug it would be shelved.”

Adverse events that occur in more than 20% of patients taking 50 mg/day over 8 weeks include chelitis, skin peeling, pruritus, rhinitis, dry skin, and alopecia. “It's a little bit less of an issue if you use the smaller dose, but nonetheless, these are significant numbers,” Dr. Leonardi said. “There are some significant, common adverse events while on this therapy.”

Despite its modest effect as monotherapy, acitretin “has a very unique mechanism of action,” he noted. “It decreases hyperproliferation of keratinocytes, it decreases inflammation directly, and it helps to normalize differentiation of the skin.”

He went on to point out that acitretin is most effective when combined with other treatments, particularly psoralen and ultraviolet light radiation (PUVA). One study of this combination demonstrated 89% clearance of psoriatic lesions at 8 weeks and 94% clearance at 12 weeks (Dertmatologica 1988;177:218-24).

A more recent trial evaluated the impact of 25 mg/day acitretin plus narrow band ultraviolet B light three times a week in 40 difficult-to-treat psoriasis patients (J. Dermatolog. Treat. 2003;14[suppl 2]:17-20). It found that 88% of patients had at least a moderate improvement of psoriasis and 73% had an improvement of at least 75%.

Dr. Leonardi disclosed he is a consultant, investigator, and member of the speakers bureau for several pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

An interview with Dr. Leonardi can be viewed by visiting www.youtube.com/user/FamilyPracticeNews#p/u/8/XA5NCq4fihQ

'There is no teratogenic threshold established for any of the oral synthetic retinoids.'

Source DR. LEONARDI

LAS VEGAS — Even though acitretin is labeled as a pregnancy category X drug, Dr. Craig L. Leonardi claimed he sees at least one patient of childbearing potential per month who is referred to him on the agent.

“I think that's a terrifically bad practice,” said Dr. Leonardi at a dermatology seminar sponsored by Skin Disease Education Foundation. “You need to think this one through.”

The chief risk posed by use of the drug in women of childbearing potential is retinoid embryopathy, which occurs in 33% of preterm infants exposed to the drug in utero. “As a consequence this drug should not be used in females of childbearing potential, which takes the drug off the list for half the population of our younger psoriasis patients,” said Dr. Leonardi, clinical professor of dermatology at St. Louis University. “Since there is no teratogenic threshold established for any of the oral synthetic retinoids, this drug just shouldn't be used in females of childbearing potential.”

The recommended acitretin pregnancy avoidance period is 3 years in the United States and 2 years in Europe.

Another downside of the drug is that it converts to detectable levels of etretinate in the presence of alcohol ingestion (based on consumption of 8 ounces by a patient weighing at least 75 kg).

A second-generation retinoid, acitretin (Soriatane, Stiefel Laboratories) is available in 10-g and 25-g gel caps. Common doses in psoriasis treatment are 25 mg twice daily, 25 mg twice daily for 1 month followed by 25 mg once daily, or starting off at 25 mg once daily.

Dr. Leonardi said he rarely prescribes acitretin as monotherapy for psoriasis because it has a modest effect on the disease, compared with cyclosporin and methotrexate, resulting in about a 50% reduction of body surface area over a period of 8-24 weeks. In addition, acitretin was approved for psoriasis based on trials involving only 275 patients, and “interpretation of the trial data is difficult,” he said. “If this were a biologic drug it would be shelved.”

Adverse events that occur in more than 20% of patients taking 50 mg/day over 8 weeks include chelitis, skin peeling, pruritus, rhinitis, dry skin, and alopecia. “It's a little bit less of an issue if you use the smaller dose, but nonetheless, these are significant numbers,” Dr. Leonardi said. “There are some significant, common adverse events while on this therapy.”

Despite its modest effect as monotherapy, acitretin “has a very unique mechanism of action,” he noted. “It decreases hyperproliferation of keratinocytes, it decreases inflammation directly, and it helps to normalize differentiation of the skin.”

He went on to point out that acitretin is most effective when combined with other treatments, particularly psoralen and ultraviolet light radiation (PUVA). One study of this combination demonstrated 89% clearance of psoriatic lesions at 8 weeks and 94% clearance at 12 weeks (Dertmatologica 1988;177:218-24).

A more recent trial evaluated the impact of 25 mg/day acitretin plus narrow band ultraviolet B light three times a week in 40 difficult-to-treat psoriasis patients (J. Dermatolog. Treat. 2003;14[suppl 2]:17-20). It found that 88% of patients had at least a moderate improvement of psoriasis and 73% had an improvement of at least 75%.

Dr. Leonardi disclosed he is a consultant, investigator, and member of the speakers bureau for several pharmaceutical companies. SDEF and this news organization are owned by Elsevier.

An interview with Dr. Leonardi can be viewed by visiting www.youtube.com/user/FamilyPracticeNews#p/u/8/XA5NCq4fihQ

'There is no teratogenic threshold established for any of the oral synthetic retinoids.'

Source DR. LEONARDI