Robert Finn

SAN FRANCISCO — A minority of patients with relapsed leukemia or lymphoma discussed advance directives with their physicians, according to a survey of 75 such patients at Virginia Commonwealth University in Richmond.

Although 35 (47%) of the patients had an advance directive, just 5 (7%) had ever discussed advance directives with their oncologist, said Dr. Thomas J. Smith at the annual Oncology Congress presented by Reed Medical Education.

“You would think that most of them would have had a discussion about advance directives, about code status with their doctor,” said Dr. Smith, the Massey Endowed Professor of Palliative Care Research and Medicine at VCU. But “in only 2 out of 75 cases had the doctor ever brought it up.”

In initial questioning, only 23% of the patients expressed a desire to discuss advance directives with their oncologist, according to the study. Yet 86% were willing to discuss advanced directives with their admitting hospitalist—a physician they had never met before—and 95% thought it would be important to have this discussion.

In attempting to learn why many patients would not want to discuss this topic with their oncologist, Dr. Smith and his colleagues questioned them closely. During this additional questioning, 48% of the patients said they would, in fact, prefer to discuss advanced directives with their oncologist, and 36% said they would prefer to discuss this topic with their primary care physician. “They want to discuss it with … the doctors who know them best,” Dr. Smith said. They're waiting for us to talk about it first.”

But physicians are often reluctant to initiate this discussion for fear of upsetting the patient or causing the patient to give up hope. In fact, advance directives have never been associated with worse survival in any study, Dr. Smith said. One study even showed that advance directives were associated with a 2.2-fold better chance of survival in patients undergoing bone marrow transplants (J. Clin. Oncol. 2007;25:5643-8).

Other studies have shown that patients who are overly optimistic about survival receive worse end-of-life care. They are more likely to be resuscitated and to die in an ICU or on a ventilator, and less likely to die at home, where most patients would prefer to die. Excessive optimism was not associated with improved survival in this study (JAMA 2008;299:2667-78).

Dr. Smith serves on the speakers bureau for Medtronic Inc., and has received honoraria from UnitedHealthcare, and grant support from the National Cancer Institute and the National Library of Medicine. Reed Medical Education and this news organization are owned by Elsevier.

SAN FRANCISCO — A minority of patients with relapsed leukemia or lymphoma discussed advance directives with their physicians, according to a survey of 75 such patients at Virginia Commonwealth University in Richmond.

Although 35 (47%) of the patients had an advance directive, just 5 (7%) had ever discussed advance directives with their oncologist, said Dr. Thomas J. Smith at the annual Oncology Congress presented by Reed Medical Education.

“You would think that most of them would have had a discussion about advance directives, about code status with their doctor,” said Dr. Smith, the Massey Endowed Professor of Palliative Care Research and Medicine at VCU. But “in only 2 out of 75 cases had the doctor ever brought it up.”

In initial questioning, only 23% of the patients expressed a desire to discuss advance directives with their oncologist, according to the study. Yet 86% were willing to discuss advanced directives with their admitting hospitalist—a physician they had never met before—and 95% thought it would be important to have this discussion.

In attempting to learn why many patients would not want to discuss this topic with their oncologist, Dr. Smith and his colleagues questioned them closely. During this additional questioning, 48% of the patients said they would, in fact, prefer to discuss advanced directives with their oncologist, and 36% said they would prefer to discuss this topic with their primary care physician. “They want to discuss it with … the doctors who know them best,” Dr. Smith said. They're waiting for us to talk about it first.”

But physicians are often reluctant to initiate this discussion for fear of upsetting the patient or causing the patient to give up hope. In fact, advance directives have never been associated with worse survival in any study, Dr. Smith said. One study even showed that advance directives were associated with a 2.2-fold better chance of survival in patients undergoing bone marrow transplants (J. Clin. Oncol. 2007;25:5643-8).

Other studies have shown that patients who are overly optimistic about survival receive worse end-of-life care. They are more likely to be resuscitated and to die in an ICU or on a ventilator, and less likely to die at home, where most patients would prefer to die. Excessive optimism was not associated with improved survival in this study (JAMA 2008;299:2667-78).

Dr. Smith serves on the speakers bureau for Medtronic Inc., and has received honoraria from UnitedHealthcare, and grant support from the National Cancer Institute and the National Library of Medicine. Reed Medical Education and this news organization are owned by Elsevier.

SAN FRANCISCO — A minority of patients with relapsed leukemia or lymphoma discussed advance directives with their physicians, according to a survey of 75 such patients at Virginia Commonwealth University in Richmond.

Although 35 (47%) of the patients had an advance directive, just 5 (7%) had ever discussed advance directives with their oncologist, said Dr. Thomas J. Smith at the annual Oncology Congress presented by Reed Medical Education.

“You would think that most of them would have had a discussion about advance directives, about code status with their doctor,” said Dr. Smith, the Massey Endowed Professor of Palliative Care Research and Medicine at VCU. But “in only 2 out of 75 cases had the doctor ever brought it up.”

In initial questioning, only 23% of the patients expressed a desire to discuss advance directives with their oncologist, according to the study. Yet 86% were willing to discuss advanced directives with their admitting hospitalist—a physician they had never met before—and 95% thought it would be important to have this discussion.

In attempting to learn why many patients would not want to discuss this topic with their oncologist, Dr. Smith and his colleagues questioned them closely. During this additional questioning, 48% of the patients said they would, in fact, prefer to discuss advanced directives with their oncologist, and 36% said they would prefer to discuss this topic with their primary care physician. “They want to discuss it with … the doctors who know them best,” Dr. Smith said. They're waiting for us to talk about it first.”

But physicians are often reluctant to initiate this discussion for fear of upsetting the patient or causing the patient to give up hope. In fact, advance directives have never been associated with worse survival in any study, Dr. Smith said. One study even showed that advance directives were associated with a 2.2-fold better chance of survival in patients undergoing bone marrow transplants (J. Clin. Oncol. 2007;25:5643-8).

Other studies have shown that patients who are overly optimistic about survival receive worse end-of-life care. They are more likely to be resuscitated and to die in an ICU or on a ventilator, and less likely to die at home, where most patients would prefer to die. Excessive optimism was not associated with improved survival in this study (JAMA 2008;299:2667-78).

Dr. Smith serves on the speakers bureau for Medtronic Inc., and has received honoraria from UnitedHealthcare, and grant support from the National Cancer Institute and the National Library of Medicine. Reed Medical Education and this news organization are owned by Elsevier.

SAN FRANCISCO — Spotting cardiotoxicity can be a challenge when clinicians follow cancer patients who experience other serious side effects of their treatment as well as the effects of their disease, cardiologist Anju Nohria acknowledged at the annual Oncology Congress presented by Reed Medical Education.

Nonetheless, the cardiac effects of new targeted therapies are often worrisome, and the toxicity of some older agents—notably the anthracyclines—has long been a concern. Dr. Nohria of the cardiovascular division of Brigham and Women's Hospital, Boston, offered the following rules of thumb for monitoring patients on these drugs in the absence of broad consensus panel guidelines on how to follow adult patients. Her suggestions are based on guidelines for following cardiotoxicity in children, she said.

Monitoring should start with a thorough history and physical examination at baseline and continue at every follow-up visit after the start of therapy, according to Dr. Nohria.

“A lot of oncologists and a lot of other practitioners rely on rales and edema as a way of looking for heart failure,” she said. “Unfortunately, if you have a slow development of chronic systolic dysfunction, you rarely see rales and edema in more than 20%-25% of patients.”

It turns out that the most sensitive physical exam finding for heart failure is an elevation in jugular venous pressure, and testing for this requires no specialized equipment. “If you sit your patient bolt upright in a chair, you should not be able to see [the] jugular venous pulsation above the level of the clavicle,” she advised. “If you can see it above the level of the clavicle, that means the patient is intravascularly volume overloaded, and … needs diuresis.”

Other symptoms of heart failure include dyspnea, orthopnea, early satiety, and exercise intolerance. Unfortunately, most of those symptoms can also be caused by chemotherapy. Orthopnea is the exception, she said, and it can be assessed simply by asking whether the patient experiences shortness of breath while lying in bed, and whether staying propped up with pillows relieves that shortness of breath.

Electrocardiography is neither sensitive nor specific in detecting cardiac complications of cancer chemotherapy, Dr. Nohria said. Myocardial biopsy, on the other hand, is highly sensitive and specific—especially for anthracycline toxicity, in which common biopsy findings include swelling of the mitochondria and sarcoplasmic reticulum along with myocyte disarray. “Unfortunately, we cannot do this on a regular basis because it's far too invasive and far too expensive,” she said.

Therefore, the next step in monitoring patients who take cardiotoxic agents is imaging, either with an echocardiogram or with a multiple-gated acquisition (MUGA) scan. “I prefer echocardiograms over MUGAs,” Dr. Nohria said. “The radiation you get with a MUGA is severalfold higher than what you see with an echo. So in terms of thinking of the long-term consequences of screening, you're better off getting an echo for these patients.” Use the same modality during subsequent follow-ups, so that the results can easily be compared.

For patients taking anthracyclines, the initial postbaseline monitoring depends on whether the patient has prior cardiac risk factors or underlying heart disease, has received chest irradiation, or is also taking paclitaxel (Taxol). Patients who meet any of those criteria should be monitored once their anthracycline dose exceeds 200 mg/m

For patients without those risk factors, Dr. Nohria said that it's safe to delay monitoring until the anthracycline dose exceeds 300 mg/m

At 3-6 months after the completion of therapy, and again at 1 year, patients on anthracycline should get an echo or MUGA. If the test is normal, “they don't need an echo more than once every 2-3 years,” Dr. Nohria said. “If they're abnormal, I want to see them in the clinic with special attention to cardiac history and physical exam every 6 months, at least until they're stable, and then perform an echo or a MUGA every year.”

Like the cardiac monitoring that's done with patients on anthracyclines, the cardiac monitoring of patients taking trastuzumab (Herceptin) should include a thorough history and physical, and an assessment of cardiac ejection fraction (EF) at baseline and every 3 months while they're on therapy. “If you get a decline in their EF or symptomatic heart failure, then treat and monitor annually after trastuzumab therapy,” Dr. Nohria said.

As for biomarker monitoring, Dr. Nohria said that the evidence is better for troponin I than for brain natriuretic peptide (BNP). An early rise in troponin I can be used as a marker to identify patients who should be monitored more closely and who should receive cardiac therapy. But although several studies have found that BNP does increase after the first dose of chemotherapy, the increase does not appear to correlate well with the development of cardiac toxicity, she said.

Dr. Nohria said she had no conflict of interest related to her talk. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Source Elsevier Global Medical News

SAN FRANCISCO — Spotting cardiotoxicity can be a challenge when clinicians follow cancer patients who experience other serious side effects of their treatment as well as the effects of their disease, cardiologist Anju Nohria acknowledged at the annual Oncology Congress presented by Reed Medical Education.

Nonetheless, the cardiac effects of new targeted therapies are often worrisome, and the toxicity of some older agents—notably the anthracyclines—has long been a concern. Dr. Nohria of the cardiovascular division of Brigham and Women's Hospital, Boston, offered the following rules of thumb for monitoring patients on these drugs in the absence of broad consensus panel guidelines on how to follow adult patients. Her suggestions are based on guidelines for following cardiotoxicity in children, she said.

Monitoring should start with a thorough history and physical examination at baseline and continue at every follow-up visit after the start of therapy, according to Dr. Nohria.

“A lot of oncologists and a lot of other practitioners rely on rales and edema as a way of looking for heart failure,” she said. “Unfortunately, if you have a slow development of chronic systolic dysfunction, you rarely see rales and edema in more than 20%-25% of patients.”

It turns out that the most sensitive physical exam finding for heart failure is an elevation in jugular venous pressure, and testing for this requires no specialized equipment. “If you sit your patient bolt upright in a chair, you should not be able to see [the] jugular venous pulsation above the level of the clavicle,” she advised. “If you can see it above the level of the clavicle, that means the patient is intravascularly volume overloaded, and … needs diuresis.”

Other symptoms of heart failure include dyspnea, orthopnea, early satiety, and exercise intolerance. Unfortunately, most of those symptoms can also be caused by chemotherapy. Orthopnea is the exception, she said, and it can be assessed simply by asking whether the patient experiences shortness of breath while lying in bed, and whether staying propped up with pillows relieves that shortness of breath.

Electrocardiography is neither sensitive nor specific in detecting cardiac complications of cancer chemotherapy, Dr. Nohria said. Myocardial biopsy, on the other hand, is highly sensitive and specific—especially for anthracycline toxicity, in which common biopsy findings include swelling of the mitochondria and sarcoplasmic reticulum along with myocyte disarray. “Unfortunately, we cannot do this on a regular basis because it's far too invasive and far too expensive,” she said.

Therefore, the next step in monitoring patients who take cardiotoxic agents is imaging, either with an echocardiogram or with a multiple-gated acquisition (MUGA) scan. “I prefer echocardiograms over MUGAs,” Dr. Nohria said. “The radiation you get with a MUGA is severalfold higher than what you see with an echo. So in terms of thinking of the long-term consequences of screening, you're better off getting an echo for these patients.” Use the same modality during subsequent follow-ups, so that the results can easily be compared.

For patients taking anthracyclines, the initial postbaseline monitoring depends on whether the patient has prior cardiac risk factors or underlying heart disease, has received chest irradiation, or is also taking paclitaxel (Taxol). Patients who meet any of those criteria should be monitored once their anthracycline dose exceeds 200 mg/m

For patients without those risk factors, Dr. Nohria said that it's safe to delay monitoring until the anthracycline dose exceeds 300 mg/m

At 3-6 months after the completion of therapy, and again at 1 year, patients on anthracycline should get an echo or MUGA. If the test is normal, “they don't need an echo more than once every 2-3 years,” Dr. Nohria said. “If they're abnormal, I want to see them in the clinic with special attention to cardiac history and physical exam every 6 months, at least until they're stable, and then perform an echo or a MUGA every year.”

Like the cardiac monitoring that's done with patients on anthracyclines, the cardiac monitoring of patients taking trastuzumab (Herceptin) should include a thorough history and physical, and an assessment of cardiac ejection fraction (EF) at baseline and every 3 months while they're on therapy. “If you get a decline in their EF or symptomatic heart failure, then treat and monitor annually after trastuzumab therapy,” Dr. Nohria said.

As for biomarker monitoring, Dr. Nohria said that the evidence is better for troponin I than for brain natriuretic peptide (BNP). An early rise in troponin I can be used as a marker to identify patients who should be monitored more closely and who should receive cardiac therapy. But although several studies have found that BNP does increase after the first dose of chemotherapy, the increase does not appear to correlate well with the development of cardiac toxicity, she said.

Dr. Nohria said she had no conflict of interest related to her talk. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Source Elsevier Global Medical News

SAN FRANCISCO — Spotting cardiotoxicity can be a challenge when clinicians follow cancer patients who experience other serious side effects of their treatment as well as the effects of their disease, cardiologist Anju Nohria acknowledged at the annual Oncology Congress presented by Reed Medical Education.

Nonetheless, the cardiac effects of new targeted therapies are often worrisome, and the toxicity of some older agents—notably the anthracyclines—has long been a concern. Dr. Nohria of the cardiovascular division of Brigham and Women's Hospital, Boston, offered the following rules of thumb for monitoring patients on these drugs in the absence of broad consensus panel guidelines on how to follow adult patients. Her suggestions are based on guidelines for following cardiotoxicity in children, she said.

Monitoring should start with a thorough history and physical examination at baseline and continue at every follow-up visit after the start of therapy, according to Dr. Nohria.

“A lot of oncologists and a lot of other practitioners rely on rales and edema as a way of looking for heart failure,” she said. “Unfortunately, if you have a slow development of chronic systolic dysfunction, you rarely see rales and edema in more than 20%-25% of patients.”

It turns out that the most sensitive physical exam finding for heart failure is an elevation in jugular venous pressure, and testing for this requires no specialized equipment. “If you sit your patient bolt upright in a chair, you should not be able to see [the] jugular venous pulsation above the level of the clavicle,” she advised. “If you can see it above the level of the clavicle, that means the patient is intravascularly volume overloaded, and … needs diuresis.”

Other symptoms of heart failure include dyspnea, orthopnea, early satiety, and exercise intolerance. Unfortunately, most of those symptoms can also be caused by chemotherapy. Orthopnea is the exception, she said, and it can be assessed simply by asking whether the patient experiences shortness of breath while lying in bed, and whether staying propped up with pillows relieves that shortness of breath.

Electrocardiography is neither sensitive nor specific in detecting cardiac complications of cancer chemotherapy, Dr. Nohria said. Myocardial biopsy, on the other hand, is highly sensitive and specific—especially for anthracycline toxicity, in which common biopsy findings include swelling of the mitochondria and sarcoplasmic reticulum along with myocyte disarray. “Unfortunately, we cannot do this on a regular basis because it's far too invasive and far too expensive,” she said.

Therefore, the next step in monitoring patients who take cardiotoxic agents is imaging, either with an echocardiogram or with a multiple-gated acquisition (MUGA) scan. “I prefer echocardiograms over MUGAs,” Dr. Nohria said. “The radiation you get with a MUGA is severalfold higher than what you see with an echo. So in terms of thinking of the long-term consequences of screening, you're better off getting an echo for these patients.” Use the same modality during subsequent follow-ups, so that the results can easily be compared.

For patients taking anthracyclines, the initial postbaseline monitoring depends on whether the patient has prior cardiac risk factors or underlying heart disease, has received chest irradiation, or is also taking paclitaxel (Taxol). Patients who meet any of those criteria should be monitored once their anthracycline dose exceeds 200 mg/m

For patients without those risk factors, Dr. Nohria said that it's safe to delay monitoring until the anthracycline dose exceeds 300 mg/m

At 3-6 months after the completion of therapy, and again at 1 year, patients on anthracycline should get an echo or MUGA. If the test is normal, “they don't need an echo more than once every 2-3 years,” Dr. Nohria said. “If they're abnormal, I want to see them in the clinic with special attention to cardiac history and physical exam every 6 months, at least until they're stable, and then perform an echo or a MUGA every year.”

Like the cardiac monitoring that's done with patients on anthracyclines, the cardiac monitoring of patients taking trastuzumab (Herceptin) should include a thorough history and physical, and an assessment of cardiac ejection fraction (EF) at baseline and every 3 months while they're on therapy. “If you get a decline in their EF or symptomatic heart failure, then treat and monitor annually after trastuzumab therapy,” Dr. Nohria said.

As for biomarker monitoring, Dr. Nohria said that the evidence is better for troponin I than for brain natriuretic peptide (BNP). An early rise in troponin I can be used as a marker to identify patients who should be monitored more closely and who should receive cardiac therapy. But although several studies have found that BNP does increase after the first dose of chemotherapy, the increase does not appear to correlate well with the development of cardiac toxicity, she said.

Dr. Nohria said she had no conflict of interest related to her talk. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Source Elsevier Global Medical News

More than three-quarters of women newly diagnosed with intraductal or stage I or II breast cancer elected breast-conserving surgery as their initial surgical therapy, according to a survey of nearly 2,000 women.

“For about the past 20 years, there have been concerns that mastectomy has been overutilized,” said Dr. Monica Morrow during a press briefing. “What we concluded from this study is that most surgeons in two large, diverse urban areas appropriately recommended surgical options for breast cancer treatment.”

The survey of 1,984 patients in Los Angeles and Detroit between June 2005 and February 2007 revealed that 66% of the women said their first surgeon recommended breast-conserving surgery (BCS). Only 17% reported that their surgeon recommended mastectomy, and another 17% reported that their surgeon did not recommend one procedure over the other, Dr. Morrow and her associates reported (JAMA 2009;302:1551–6).

“From a practical point of view, what these results imply is that if we are interested in decreasing the mastectomy rate, approaches which have been advocated—such as more extensive and expensive preoperative evaluations with additional imaging modalities, such as magnetic resonance imaging—are unlikely to have an impact on the mastectomy rate,” noted Dr. Morrow, the lead author of the study and a surgeon at Memorial Sloan-Kettering Cancer Center, New York.

The study, funded by the National Cancer Institute, involved women aged 20–79 years with newly diagnosed ductal carcinoma in situ or invasive breast cancer in stages I or II. Women were identified through reports to NCI's Surveillance, Epidemiology, and End Results (SEER) registries for the metropolitan areas of Los Angeles and Detroit. Investigators sent surveys to 3,133 women, and 2,290 returned the completed surveys for a response rate of 73%. Of the returned surveys, 306 were excluded.

Of the 341 patients whose surgeons recommended mastectomy, 67% reported that they had a contraindication to BCS.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon. Only 20% of patients whose first surgeon recommended mastectomy received a recommendation for BCS from the second surgeon. Only 12% of patients whose first surgeon recommended BCS received a recommendation for mastectomy from the second surgeon, noted Dr. Morrow, who said she had no financial disclosures regarding the study.

The women tended to follow their surgeons' recommendations. Of the patients who did not get a second opinion, only 2.1% received mastectomy when their surgeon recommended BCS, and 89% of patients received mastectomy when their surgeon recommended it. Only 1.9% of patients received mastectomy when two surgeons recommended BCS, and 78% of patients received mastectomy when both surgeons recommended it.

Of patients who received BCS as initial therapy, 62% received no further surgery, 26% underwent reexcision only, 4% received reexcision followed by mastectomy, and 8% received mastectomy only.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon.

Source DR. MORROW

More than three-quarters of women newly diagnosed with intraductal or stage I or II breast cancer elected breast-conserving surgery as their initial surgical therapy, according to a survey of nearly 2,000 women.

“For about the past 20 years, there have been concerns that mastectomy has been overutilized,” said Dr. Monica Morrow during a press briefing. “What we concluded from this study is that most surgeons in two large, diverse urban areas appropriately recommended surgical options for breast cancer treatment.”

The survey of 1,984 patients in Los Angeles and Detroit between June 2005 and February 2007 revealed that 66% of the women said their first surgeon recommended breast-conserving surgery (BCS). Only 17% reported that their surgeon recommended mastectomy, and another 17% reported that their surgeon did not recommend one procedure over the other, Dr. Morrow and her associates reported (JAMA 2009;302:1551–6).

“From a practical point of view, what these results imply is that if we are interested in decreasing the mastectomy rate, approaches which have been advocated—such as more extensive and expensive preoperative evaluations with additional imaging modalities, such as magnetic resonance imaging—are unlikely to have an impact on the mastectomy rate,” noted Dr. Morrow, the lead author of the study and a surgeon at Memorial Sloan-Kettering Cancer Center, New York.

The study, funded by the National Cancer Institute, involved women aged 20–79 years with newly diagnosed ductal carcinoma in situ or invasive breast cancer in stages I or II. Women were identified through reports to NCI's Surveillance, Epidemiology, and End Results (SEER) registries for the metropolitan areas of Los Angeles and Detroit. Investigators sent surveys to 3,133 women, and 2,290 returned the completed surveys for a response rate of 73%. Of the returned surveys, 306 were excluded.

Of the 341 patients whose surgeons recommended mastectomy, 67% reported that they had a contraindication to BCS.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon. Only 20% of patients whose first surgeon recommended mastectomy received a recommendation for BCS from the second surgeon. Only 12% of patients whose first surgeon recommended BCS received a recommendation for mastectomy from the second surgeon, noted Dr. Morrow, who said she had no financial disclosures regarding the study.

The women tended to follow their surgeons' recommendations. Of the patients who did not get a second opinion, only 2.1% received mastectomy when their surgeon recommended BCS, and 89% of patients received mastectomy when their surgeon recommended it. Only 1.9% of patients received mastectomy when two surgeons recommended BCS, and 78% of patients received mastectomy when both surgeons recommended it.

Of patients who received BCS as initial therapy, 62% received no further surgery, 26% underwent reexcision only, 4% received reexcision followed by mastectomy, and 8% received mastectomy only.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon.

Source DR. MORROW

More than three-quarters of women newly diagnosed with intraductal or stage I or II breast cancer elected breast-conserving surgery as their initial surgical therapy, according to a survey of nearly 2,000 women.

“For about the past 20 years, there have been concerns that mastectomy has been overutilized,” said Dr. Monica Morrow during a press briefing. “What we concluded from this study is that most surgeons in two large, diverse urban areas appropriately recommended surgical options for breast cancer treatment.”

The survey of 1,984 patients in Los Angeles and Detroit between June 2005 and February 2007 revealed that 66% of the women said their first surgeon recommended breast-conserving surgery (BCS). Only 17% reported that their surgeon recommended mastectomy, and another 17% reported that their surgeon did not recommend one procedure over the other, Dr. Morrow and her associates reported (JAMA 2009;302:1551–6).

“From a practical point of view, what these results imply is that if we are interested in decreasing the mastectomy rate, approaches which have been advocated—such as more extensive and expensive preoperative evaluations with additional imaging modalities, such as magnetic resonance imaging—are unlikely to have an impact on the mastectomy rate,” noted Dr. Morrow, the lead author of the study and a surgeon at Memorial Sloan-Kettering Cancer Center, New York.

The study, funded by the National Cancer Institute, involved women aged 20–79 years with newly diagnosed ductal carcinoma in situ or invasive breast cancer in stages I or II. Women were identified through reports to NCI's Surveillance, Epidemiology, and End Results (SEER) registries for the metropolitan areas of Los Angeles and Detroit. Investigators sent surveys to 3,133 women, and 2,290 returned the completed surveys for a response rate of 73%. Of the returned surveys, 306 were excluded.

Of the 341 patients whose surgeons recommended mastectomy, 67% reported that they had a contraindication to BCS.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon. Only 20% of patients whose first surgeon recommended mastectomy received a recommendation for BCS from the second surgeon. Only 12% of patients whose first surgeon recommended BCS received a recommendation for mastectomy from the second surgeon, noted Dr. Morrow, who said she had no financial disclosures regarding the study.

The women tended to follow their surgeons' recommendations. Of the patients who did not get a second opinion, only 2.1% received mastectomy when their surgeon recommended BCS, and 89% of patients received mastectomy when their surgeon recommended it. Only 1.9% of patients received mastectomy when two surgeons recommended BCS, and 78% of patients received mastectomy when both surgeons recommended it.

Of patients who received BCS as initial therapy, 62% received no further surgery, 26% underwent reexcision only, 4% received reexcision followed by mastectomy, and 8% received mastectomy only.

Of the 19% of patients who sought a second opinion, differing recommendations were relatively uncommon.

Source DR. MORROW

SAN FRANCISCO — Infants most often acquire Staphylococcus aureus infections from their mothers horizontally after birth and not vertically during birth, based on a prospective, longitudinal study of 158 pregnant women and their offspring.

Of the participating women, 54 (34%) were S. aureus carriers, and 17 of the children born to them (31%) acquired S. aureus before discharge, Dr. Eyal Leshem and colleagues at Chaim Sheba Medical Center, Tel Hashomer, Israel, wrote in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

By contrast, only 3% of the children born to noncarrier mothers acquired S. aureus. The investigators found that the mother's carriage status was a very strong predictor of the infant's status. Children born to carriers were 22 times more likely to acquire S. aureus than other children.

The investigators controlled for the sex of the child, carriage status of the mother, breastfeeding, gestational age, antibiotic treatment, type of delivery, and smoking status. This increase in risk was highly statistically significant.

The only other statistically significant predictor of mother-to-infant transmission was smoking status. Children born to mothers who smoked before or during pregnancy were four times more likely to acquire S. aureus.

Of the 54 maternal carriers, 38 were nasal carriers, 9 were vaginal carriers, and 7 were both vaginal and nasal carriers. Among 11 of the newborns who acquired S. aureus from their carrier mothers, 9 had strains that were genetically identical to the mother's nasal strain, but only 2 had strains identical to the mother's vaginal strain. This suggests that the transmission was horizontal rather than vertical.

Two other pieces of evidence supported the hypothesis that most transmission was horizontal. Only 5% of newborns had acquired S. aureus by 1 hour after birth, but this figure increased to 8% at 24–48 hours and to 12% by 72–100 hours.

In addition, there were no significant differences in transmission rates between infants born vaginally and those born by cesarean section.

If a vertical transmission were dominant, one would expect a greater rate of transmission in vaginal births, Dr. Lesham said.

Not all infants acquired a strain identical to the mother's. Five infants acquired a different strain, but in two of those cases that strain was later replaced by a maternal strain.

The investigators reported no conflicts of interest related to their study.

SAN FRANCISCO — Infants most often acquire Staphylococcus aureus infections from their mothers horizontally after birth and not vertically during birth, based on a prospective, longitudinal study of 158 pregnant women and their offspring.

Of the participating women, 54 (34%) were S. aureus carriers, and 17 of the children born to them (31%) acquired S. aureus before discharge, Dr. Eyal Leshem and colleagues at Chaim Sheba Medical Center, Tel Hashomer, Israel, wrote in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

By contrast, only 3% of the children born to noncarrier mothers acquired S. aureus. The investigators found that the mother's carriage status was a very strong predictor of the infant's status. Children born to carriers were 22 times more likely to acquire S. aureus than other children.

The investigators controlled for the sex of the child, carriage status of the mother, breastfeeding, gestational age, antibiotic treatment, type of delivery, and smoking status. This increase in risk was highly statistically significant.

The only other statistically significant predictor of mother-to-infant transmission was smoking status. Children born to mothers who smoked before or during pregnancy were four times more likely to acquire S. aureus.

Of the 54 maternal carriers, 38 were nasal carriers, 9 were vaginal carriers, and 7 were both vaginal and nasal carriers. Among 11 of the newborns who acquired S. aureus from their carrier mothers, 9 had strains that were genetically identical to the mother's nasal strain, but only 2 had strains identical to the mother's vaginal strain. This suggests that the transmission was horizontal rather than vertical.

Two other pieces of evidence supported the hypothesis that most transmission was horizontal. Only 5% of newborns had acquired S. aureus by 1 hour after birth, but this figure increased to 8% at 24–48 hours and to 12% by 72–100 hours.

In addition, there were no significant differences in transmission rates between infants born vaginally and those born by cesarean section.

If a vertical transmission were dominant, one would expect a greater rate of transmission in vaginal births, Dr. Lesham said.

Not all infants acquired a strain identical to the mother's. Five infants acquired a different strain, but in two of those cases that strain was later replaced by a maternal strain.

The investigators reported no conflicts of interest related to their study.

SAN FRANCISCO — Infants most often acquire Staphylococcus aureus infections from their mothers horizontally after birth and not vertically during birth, based on a prospective, longitudinal study of 158 pregnant women and their offspring.

Of the participating women, 54 (34%) were S. aureus carriers, and 17 of the children born to them (31%) acquired S. aureus before discharge, Dr. Eyal Leshem and colleagues at Chaim Sheba Medical Center, Tel Hashomer, Israel, wrote in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

By contrast, only 3% of the children born to noncarrier mothers acquired S. aureus. The investigators found that the mother's carriage status was a very strong predictor of the infant's status. Children born to carriers were 22 times more likely to acquire S. aureus than other children.

The investigators controlled for the sex of the child, carriage status of the mother, breastfeeding, gestational age, antibiotic treatment, type of delivery, and smoking status. This increase in risk was highly statistically significant.

The only other statistically significant predictor of mother-to-infant transmission was smoking status. Children born to mothers who smoked before or during pregnancy were four times more likely to acquire S. aureus.

Of the 54 maternal carriers, 38 were nasal carriers, 9 were vaginal carriers, and 7 were both vaginal and nasal carriers. Among 11 of the newborns who acquired S. aureus from their carrier mothers, 9 had strains that were genetically identical to the mother's nasal strain, but only 2 had strains identical to the mother's vaginal strain. This suggests that the transmission was horizontal rather than vertical.

Two other pieces of evidence supported the hypothesis that most transmission was horizontal. Only 5% of newborns had acquired S. aureus by 1 hour after birth, but this figure increased to 8% at 24–48 hours and to 12% by 72–100 hours.

In addition, there were no significant differences in transmission rates between infants born vaginally and those born by cesarean section.

If a vertical transmission were dominant, one would expect a greater rate of transmission in vaginal births, Dr. Lesham said.

Not all infants acquired a strain identical to the mother's. Five infants acquired a different strain, but in two of those cases that strain was later replaced by a maternal strain.

The investigators reported no conflicts of interest related to their study.

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

"Parents want to go read up on these things, and they want to know how long it's going to take to go away," Dr. Mancini said in an interview. "If you can characterize it … it's helpful for parents to know. At least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later."

Clinicians have learned to keep an eye out for the truly bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever.

At the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF), Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed common exanthems, and many that aren't so common. But he paid special attention to three of the newer or atypical exanthems: Arcanobacterium haemolyticum, unilateral laterothoracic exanthem, and acute generalized exanthematous pustulosis (AGEP).

A. haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Unilateral Laterothoracic Exanthem

Most physicians "have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis," Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6–8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

"It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis," he said. It's self-limited, but children do tend to appear more toxic with AGEP than with some other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated. Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

Acute generalized exanthematous pustulosis onset can be sudden.

Source Courtesy Dr. Anthony J. Mancini

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

"Parents want to go read up on these things, and they want to know how long it's going to take to go away," Dr. Mancini said in an interview. "If you can characterize it … it's helpful for parents to know. At least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later."

Clinicians have learned to keep an eye out for the truly bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever.

At the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF), Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed common exanthems, and many that aren't so common. But he paid special attention to three of the newer or atypical exanthems: Arcanobacterium haemolyticum, unilateral laterothoracic exanthem, and acute generalized exanthematous pustulosis (AGEP).

A. haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Unilateral Laterothoracic Exanthem

Most physicians "have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis," Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6–8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

"It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis," he said. It's self-limited, but children do tend to appear more toxic with AGEP than with some other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated. Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

Acute generalized exanthematous pustulosis onset can be sudden.

Source Courtesy Dr. Anthony J. Mancini

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

"Parents want to go read up on these things, and they want to know how long it's going to take to go away," Dr. Mancini said in an interview. "If you can characterize it … it's helpful for parents to know. At least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later."

Clinicians have learned to keep an eye out for the truly bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever.

At the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF), Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed common exanthems, and many that aren't so common. But he paid special attention to three of the newer or atypical exanthems: Arcanobacterium haemolyticum, unilateral laterothoracic exanthem, and acute generalized exanthematous pustulosis (AGEP).

A. haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Unilateral Laterothoracic Exanthem

Most physicians "have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis," Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6–8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

"It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis," he said. It's self-limited, but children do tend to appear more toxic with AGEP than with some other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated. Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

Acute generalized exanthematous pustulosis onset can be sudden.

Source Courtesy Dr. Anthony J. Mancini

New genetic research is yielding some important clues into the puzzling condition of alopecia areata, Dr. Maria Hordinsky reported at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

By doing whole-genome analysis on thousands of samples gathered over the last 9 years, investigators have found four genes associated with the disease. Surprisingly, none of the genes is implicated in psoriasis, which has long been considered a risk factor for alopecia areata. Conversely, none of the genes associated with psoriasis appears to be implicated in alopecia areata. Investigators announced the findings this year at the annual meeting of the Society for Investigative Dermatology in Montreal.

These findings have important consequences for treatment and research, according to Dr. Hordinsky, chair of the dermatology department at the University of Minnesota, Minneapolis.

"We've all been scratching our heads for the past couple of years wondering why on Earth the new biologics that work so well in psoriasis are not working in this disease," she said. "So now with this data, maybe one possibility is that the diseases are just completely different in the way they're molecularly structured. The thinking has changed in the past couple of months. If you were to start a clinical trial today in alopecia areata, based on the new information, you probably wouldn't pick some of the biologics that were picked a few years ago."

For now, though, Dr. Hordinsky emphasized that there is no "best" treatment for alopecia areata. Patients with patchy alopecia areata sometimes respond to topical or intralesional corticosteroids, minoxidil solution, anthralin, steroid-containing shampoos, excimer laser therapy, or combination treatment.

For extensive alopecia areata, Dr. Hordinsky suggested prednisone, topical minoxidil, PUVA, immunotherapy, pulse methylprednisolone, narrow-band UVB, or combination therapy. Other possible treatments include cyclosporine, tacrolimus, dapsone, sulfasalazine, hydroxychloroquine, retinoids, and biologics.

She recommended focusing on the patient's nail to diagnose alopecia areata. Between 10% and 66% of patients with alopecia areata have nail abnormalities, and these abnormalities may precede, follow, or occur concurrently with hair loss, she noted. Nail pitting is the most common abnormality, but there may also be longitudinal ridging, koilonychia, brittle nails, onycholysis, onychomadesis, and periungual erythema.

Dr. Hordinsky's presentation concentrated on alopecia areata in children, but she said that there are few differences in the pathophysiology of pediatric versus adult disease. "It's a disease that affects all ages, all races, and is seen equally in males and females."

The difference in children involves the psychosocial aspects of the disease, and physicians need to be sensitive to these issues. "It's not like body dysmorphic disorder, where people get fixated on something that's not quite right, worrying that their nose is imperfect or something," she pointed out. "This disease can result in very rapid, and sometimes dramatic, alteration in physical appearance. So there's a psychological adaptation that has to take place. Patients have to figure out: How do you live with this disease? How do you make yourself more normal looking so you fit better into your age group, into your peer groups, into school?"

Physicians can refer patients and their families to the National Alopecia Areata Foundation (www.naaf.org

She encouraged all physicians to register patients—and their families—with the national Alopecia Areata Registry (www.alopeciaareataregistry.org

Dr. Hordinsky did not disclose relevant conflicts of interest in her presentation. SDEF and this news organization are owned by Elsevier.

A child with alopecia areata universalis is shown prior to any treatment.

Source Photos courtesy Dr. R. Berrada

The child had significant hair growth after undergoing 50 sessions of PUVA therapy.

Source Photos courtesy Dr. R. Berrada

New genetic research is yielding some important clues into the puzzling condition of alopecia areata, Dr. Maria Hordinsky reported at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

By doing whole-genome analysis on thousands of samples gathered over the last 9 years, investigators have found four genes associated with the disease. Surprisingly, none of the genes is implicated in psoriasis, which has long been considered a risk factor for alopecia areata. Conversely, none of the genes associated with psoriasis appears to be implicated in alopecia areata. Investigators announced the findings this year at the annual meeting of the Society for Investigative Dermatology in Montreal.

These findings have important consequences for treatment and research, according to Dr. Hordinsky, chair of the dermatology department at the University of Minnesota, Minneapolis.

"We've all been scratching our heads for the past couple of years wondering why on Earth the new biologics that work so well in psoriasis are not working in this disease," she said. "So now with this data, maybe one possibility is that the diseases are just completely different in the way they're molecularly structured. The thinking has changed in the past couple of months. If you were to start a clinical trial today in alopecia areata, based on the new information, you probably wouldn't pick some of the biologics that were picked a few years ago."

For now, though, Dr. Hordinsky emphasized that there is no "best" treatment for alopecia areata. Patients with patchy alopecia areata sometimes respond to topical or intralesional corticosteroids, minoxidil solution, anthralin, steroid-containing shampoos, excimer laser therapy, or combination treatment.

For extensive alopecia areata, Dr. Hordinsky suggested prednisone, topical minoxidil, PUVA, immunotherapy, pulse methylprednisolone, narrow-band UVB, or combination therapy. Other possible treatments include cyclosporine, tacrolimus, dapsone, sulfasalazine, hydroxychloroquine, retinoids, and biologics.

She recommended focusing on the patient's nail to diagnose alopecia areata. Between 10% and 66% of patients with alopecia areata have nail abnormalities, and these abnormalities may precede, follow, or occur concurrently with hair loss, she noted. Nail pitting is the most common abnormality, but there may also be longitudinal ridging, koilonychia, brittle nails, onycholysis, onychomadesis, and periungual erythema.

Dr. Hordinsky's presentation concentrated on alopecia areata in children, but she said that there are few differences in the pathophysiology of pediatric versus adult disease. "It's a disease that affects all ages, all races, and is seen equally in males and females."

The difference in children involves the psychosocial aspects of the disease, and physicians need to be sensitive to these issues. "It's not like body dysmorphic disorder, where people get fixated on something that's not quite right, worrying that their nose is imperfect or something," she pointed out. "This disease can result in very rapid, and sometimes dramatic, alteration in physical appearance. So there's a psychological adaptation that has to take place. Patients have to figure out: How do you live with this disease? How do you make yourself more normal looking so you fit better into your age group, into your peer groups, into school?"

Physicians can refer patients and their families to the National Alopecia Areata Foundation (www.naaf.org

She encouraged all physicians to register patients—and their families—with the national Alopecia Areata Registry (www.alopeciaareataregistry.org

Dr. Hordinsky did not disclose relevant conflicts of interest in her presentation. SDEF and this news organization are owned by Elsevier.

A child with alopecia areata universalis is shown prior to any treatment.

Source Photos courtesy Dr. R. Berrada

The child had significant hair growth after undergoing 50 sessions of PUVA therapy.

Source Photos courtesy Dr. R. Berrada

New genetic research is yielding some important clues into the puzzling condition of alopecia areata, Dr. Maria Hordinsky reported at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

By doing whole-genome analysis on thousands of samples gathered over the last 9 years, investigators have found four genes associated with the disease. Surprisingly, none of the genes is implicated in psoriasis, which has long been considered a risk factor for alopecia areata. Conversely, none of the genes associated with psoriasis appears to be implicated in alopecia areata. Investigators announced the findings this year at the annual meeting of the Society for Investigative Dermatology in Montreal.

These findings have important consequences for treatment and research, according to Dr. Hordinsky, chair of the dermatology department at the University of Minnesota, Minneapolis.

"We've all been scratching our heads for the past couple of years wondering why on Earth the new biologics that work so well in psoriasis are not working in this disease," she said. "So now with this data, maybe one possibility is that the diseases are just completely different in the way they're molecularly structured. The thinking has changed in the past couple of months. If you were to start a clinical trial today in alopecia areata, based on the new information, you probably wouldn't pick some of the biologics that were picked a few years ago."

For now, though, Dr. Hordinsky emphasized that there is no "best" treatment for alopecia areata. Patients with patchy alopecia areata sometimes respond to topical or intralesional corticosteroids, minoxidil solution, anthralin, steroid-containing shampoos, excimer laser therapy, or combination treatment.

For extensive alopecia areata, Dr. Hordinsky suggested prednisone, topical minoxidil, PUVA, immunotherapy, pulse methylprednisolone, narrow-band UVB, or combination therapy. Other possible treatments include cyclosporine, tacrolimus, dapsone, sulfasalazine, hydroxychloroquine, retinoids, and biologics.

She recommended focusing on the patient's nail to diagnose alopecia areata. Between 10% and 66% of patients with alopecia areata have nail abnormalities, and these abnormalities may precede, follow, or occur concurrently with hair loss, she noted. Nail pitting is the most common abnormality, but there may also be longitudinal ridging, koilonychia, brittle nails, onycholysis, onychomadesis, and periungual erythema.

Dr. Hordinsky's presentation concentrated on alopecia areata in children, but she said that there are few differences in the pathophysiology of pediatric versus adult disease. "It's a disease that affects all ages, all races, and is seen equally in males and females."

The difference in children involves the psychosocial aspects of the disease, and physicians need to be sensitive to these issues. "It's not like body dysmorphic disorder, where people get fixated on something that's not quite right, worrying that their nose is imperfect or something," she pointed out. "This disease can result in very rapid, and sometimes dramatic, alteration in physical appearance. So there's a psychological adaptation that has to take place. Patients have to figure out: How do you live with this disease? How do you make yourself more normal looking so you fit better into your age group, into your peer groups, into school?"

Physicians can refer patients and their families to the National Alopecia Areata Foundation (www.naaf.org

She encouraged all physicians to register patients—and their families—with the national Alopecia Areata Registry (www.alopeciaareataregistry.org

Dr. Hordinsky did not disclose relevant conflicts of interest in her presentation. SDEF and this news organization are owned by Elsevier.

A child with alopecia areata universalis is shown prior to any treatment.

Source Photos courtesy Dr. R. Berrada

The child had significant hair growth after undergoing 50 sessions of PUVA therapy.

Source Photos courtesy Dr. R. Berrada

SAN FRANCISCO — A short course of therapy with torezolid phosphate cured virtually all patients with Staphylococcus aureus—based severe complicated skin and skin structure infections in a randomized, double-blind, phase II study.

A second-generation oxazolidinone related to linezolid, torezolid phosphate is a prodrug that can be given orally once per day, Dr. Philippe Prokocimer said in an interview. Dr. Prokocimer is medical director of Trius Therapeutics, the San Diego–based company that is developing the drug. He was one of the authors of the study, which was presented in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

The study involved 192 patients with S. aureus infections who were randomized to receive 200 mg, 300 mg, or 400 mg of torezolid phosphate once a day for 5–7 days. All patients had severe complicated skin and skin structure infections (cSSSI, also called acute bacterial skin structure infections), defined as skin infections that were 5 cm or greater in diameter and/or included systemic signs of infection. Patients with uncomplicated disease or with infections requiring gram-negative coverage were excluded, as were immunocompromised patients and those who had used antibiotics for more than 24 hours within 96 hours of the start of the study.

The clinical outcomes were similar in all dosage groups. Of the patients whose lesions were microbiologically evaluable, 96% achieved a clinical cure, including 95.7% of the patients with methicillin-susceptible S. aureus infections and 96.9% of the patients with methicillin-resistant S. aureus infections.

Five of the patients in the study experienced serious adverse events, but only one of these could have been drug related—a case of acute cholecystitis in an obese 57-year-old woman 2 days after the end of therapy. All other treatment-emergent adverse events were mild or moderate, with nausea the most common (19% of patients). The investigators saw no clinically significant changes in QTc.

"The side effect profile is stellar," Dr. Prokocimer said. "When we increase the dose, we don't see a dose-related increase in the incidence of side effects."

He noted that unlike linezolid, the 200-mg dose of torezolid phosphate had virtually no effects on patients' laboratory values and showed no evidence of immunosuppression. The 200-mg dose will be the subject of two pivotal phase III studies, due to begin in 2010.

SAN FRANCISCO — A short course of therapy with torezolid phosphate cured virtually all patients with Staphylococcus aureus—based severe complicated skin and skin structure infections in a randomized, double-blind, phase II study.

A second-generation oxazolidinone related to linezolid, torezolid phosphate is a prodrug that can be given orally once per day, Dr. Philippe Prokocimer said in an interview. Dr. Prokocimer is medical director of Trius Therapeutics, the San Diego–based company that is developing the drug. He was one of the authors of the study, which was presented in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

The study involved 192 patients with S. aureus infections who were randomized to receive 200 mg, 300 mg, or 400 mg of torezolid phosphate once a day for 5–7 days. All patients had severe complicated skin and skin structure infections (cSSSI, also called acute bacterial skin structure infections), defined as skin infections that were 5 cm or greater in diameter and/or included systemic signs of infection. Patients with uncomplicated disease or with infections requiring gram-negative coverage were excluded, as were immunocompromised patients and those who had used antibiotics for more than 24 hours within 96 hours of the start of the study.

The clinical outcomes were similar in all dosage groups. Of the patients whose lesions were microbiologically evaluable, 96% achieved a clinical cure, including 95.7% of the patients with methicillin-susceptible S. aureus infections and 96.9% of the patients with methicillin-resistant S. aureus infections.

Five of the patients in the study experienced serious adverse events, but only one of these could have been drug related—a case of acute cholecystitis in an obese 57-year-old woman 2 days after the end of therapy. All other treatment-emergent adverse events were mild or moderate, with nausea the most common (19% of patients). The investigators saw no clinically significant changes in QTc.

"The side effect profile is stellar," Dr. Prokocimer said. "When we increase the dose, we don't see a dose-related increase in the incidence of side effects."

He noted that unlike linezolid, the 200-mg dose of torezolid phosphate had virtually no effects on patients' laboratory values and showed no evidence of immunosuppression. The 200-mg dose will be the subject of two pivotal phase III studies, due to begin in 2010.

SAN FRANCISCO — A short course of therapy with torezolid phosphate cured virtually all patients with Staphylococcus aureus—based severe complicated skin and skin structure infections in a randomized, double-blind, phase II study.

A second-generation oxazolidinone related to linezolid, torezolid phosphate is a prodrug that can be given orally once per day, Dr. Philippe Prokocimer said in an interview. Dr. Prokocimer is medical director of Trius Therapeutics, the San Diego–based company that is developing the drug. He was one of the authors of the study, which was presented in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.

The study involved 192 patients with S. aureus infections who were randomized to receive 200 mg, 300 mg, or 400 mg of torezolid phosphate once a day for 5–7 days. All patients had severe complicated skin and skin structure infections (cSSSI, also called acute bacterial skin structure infections), defined as skin infections that were 5 cm or greater in diameter and/or included systemic signs of infection. Patients with uncomplicated disease or with infections requiring gram-negative coverage were excluded, as were immunocompromised patients and those who had used antibiotics for more than 24 hours within 96 hours of the start of the study.

The clinical outcomes were similar in all dosage groups. Of the patients whose lesions were microbiologically evaluable, 96% achieved a clinical cure, including 95.7% of the patients with methicillin-susceptible S. aureus infections and 96.9% of the patients with methicillin-resistant S. aureus infections.

Five of the patients in the study experienced serious adverse events, but only one of these could have been drug related—a case of acute cholecystitis in an obese 57-year-old woman 2 days after the end of therapy. All other treatment-emergent adverse events were mild or moderate, with nausea the most common (19% of patients). The investigators saw no clinically significant changes in QTc.

"The side effect profile is stellar," Dr. Prokocimer said. "When we increase the dose, we don't see a dose-related increase in the incidence of side effects."

He noted that unlike linezolid, the 200-mg dose of torezolid phosphate had virtually no effects on patients' laboratory values and showed no evidence of immunosuppression. The 200-mg dose will be the subject of two pivotal phase III studies, due to begin in 2010.

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Aside from their bronchiolitis, all 74 were healthy.

The investigators from the University of Milan collected specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B. As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” wrote the investigators, who reported that they had no conflicts of interest.

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Aside from their bronchiolitis, all 74 were healthy.

The investigators from the University of Milan collected specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B. As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” wrote the investigators, who reported that they had no conflicts of interest.

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Aside from their bronchiolitis, all 74 were healthy.

The investigators from the University of Milan collected specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B. As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” wrote the investigators, who reported that they had no conflicts of interest.

SAN FRANCISCO — Many children with diabetes do quite well on insulin pumps, but patient selection is important, according to Dr. Stephen E. Gitelman.

“We studied toddlers. We studied teens. It turns out [pumps] can work well on any age group,” he said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco. “The people that do best are those where the child is motivated to use the pump and there's a supportive and involved family who's going to help him.”

Pumps can work well in toddlers with newly diagnosed type 1 diabetes, or teenagers who have been giving themselves injections for years. Pumps are suitable in children with low HbA_1c or high HbA_1c levels. And pumps are even suitable in some children with type 2 diabetes who have failed oral medication, said Dr. Gitelman, a pediatric endocrinologist at the university.

Although a pump may provide more glycemic control than is necessary in the early course of diabetes, Dr. Gitelman said that there is evidence that tighter glycemic control may preserve beta-cell function.

Dr. Gitelman offered several tips for selecting suitable pump candidates. The successful pediatric pump user will have already shown solid diabetes self-management skills (e.g., the child will be monitoring glucose four or more times each day and will be counting carbohydrates).

The child needs to have sufficient manual dexterity to operate the pump, and cannot be technophobic.

Dr. Gitelman said about one-third of the children with diabetes in his practice are using the pump successfully. Most children are eager for the pump because they know it means no more shots. Other benefits include better overall control, less risk of hypoglycemia, and improved quality of life.

However, use of the pump carries risks, he said. For example, infections at the catheter placement site can be a problem. The pump is used only with short-acting insulin. If something goes wrong with the pump or the catheter gets dislodged, the child can be in diabetic ketoacidosis within just 4–6 hours.

And some children don't like wearing the device, which is difficult to conceal. When people notice it they frequently ask questions, requiring the child to launch into a discussion of diabetes.

And then there are the financial issues. A pump costs $5,000–$6,000, and supplies run about $100 per month. Fortunately, most insurers pick up this cost for children, he said.

“The more we use pumps, the more we start to feel that the bottom line is anyone who is on insulin therapy could benefit from them,” said Dr. Gitelman, who did not disclose any conflicts of interest.

SAN FRANCISCO — Many children with diabetes do quite well on insulin pumps, but patient selection is important, according to Dr. Stephen E. Gitelman.

“We studied toddlers. We studied teens. It turns out [pumps] can work well on any age group,” he said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco. “The people that do best are those where the child is motivated to use the pump and there's a supportive and involved family who's going to help him.”

Pumps can work well in toddlers with newly diagnosed type 1 diabetes, or teenagers who have been giving themselves injections for years. Pumps are suitable in children with low HbA_1c or high HbA_1c levels. And pumps are even suitable in some children with type 2 diabetes who have failed oral medication, said Dr. Gitelman, a pediatric endocrinologist at the university.

Although a pump may provide more glycemic control than is necessary in the early course of diabetes, Dr. Gitelman said that there is evidence that tighter glycemic control may preserve beta-cell function.

Dr. Gitelman offered several tips for selecting suitable pump candidates. The successful pediatric pump user will have already shown solid diabetes self-management skills (e.g., the child will be monitoring glucose four or more times each day and will be counting carbohydrates).

The child needs to have sufficient manual dexterity to operate the pump, and cannot be technophobic.

Dr. Gitelman said about one-third of the children with diabetes in his practice are using the pump successfully. Most children are eager for the pump because they know it means no more shots. Other benefits include better overall control, less risk of hypoglycemia, and improved quality of life.

However, use of the pump carries risks, he said. For example, infections at the catheter placement site can be a problem. The pump is used only with short-acting insulin. If something goes wrong with the pump or the catheter gets dislodged, the child can be in diabetic ketoacidosis within just 4–6 hours.

And some children don't like wearing the device, which is difficult to conceal. When people notice it they frequently ask questions, requiring the child to launch into a discussion of diabetes.

And then there are the financial issues. A pump costs $5,000–$6,000, and supplies run about $100 per month. Fortunately, most insurers pick up this cost for children, he said.

“The more we use pumps, the more we start to feel that the bottom line is anyone who is on insulin therapy could benefit from them,” said Dr. Gitelman, who did not disclose any conflicts of interest.

SAN FRANCISCO — Many children with diabetes do quite well on insulin pumps, but patient selection is important, according to Dr. Stephen E. Gitelman.

“We studied toddlers. We studied teens. It turns out [pumps] can work well on any age group,” he said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco. “The people that do best are those where the child is motivated to use the pump and there's a supportive and involved family who's going to help him.”

Pumps can work well in toddlers with newly diagnosed type 1 diabetes, or teenagers who have been giving themselves injections for years. Pumps are suitable in children with low HbA_1c or high HbA_1c levels. And pumps are even suitable in some children with type 2 diabetes who have failed oral medication, said Dr. Gitelman, a pediatric endocrinologist at the university.

Although a pump may provide more glycemic control than is necessary in the early course of diabetes, Dr. Gitelman said that there is evidence that tighter glycemic control may preserve beta-cell function.

Dr. Gitelman offered several tips for selecting suitable pump candidates. The successful pediatric pump user will have already shown solid diabetes self-management skills (e.g., the child will be monitoring glucose four or more times each day and will be counting carbohydrates).

The child needs to have sufficient manual dexterity to operate the pump, and cannot be technophobic.

Dr. Gitelman said about one-third of the children with diabetes in his practice are using the pump successfully. Most children are eager for the pump because they know it means no more shots. Other benefits include better overall control, less risk of hypoglycemia, and improved quality of life.

However, use of the pump carries risks, he said. For example, infections at the catheter placement site can be a problem. The pump is used only with short-acting insulin. If something goes wrong with the pump or the catheter gets dislodged, the child can be in diabetic ketoacidosis within just 4–6 hours.

And some children don't like wearing the device, which is difficult to conceal. When people notice it they frequently ask questions, requiring the child to launch into a discussion of diabetes.

And then there are the financial issues. A pump costs $5,000–$6,000, and supplies run about $100 per month. Fortunately, most insurers pick up this cost for children, he said.

“The more we use pumps, the more we start to feel that the bottom line is anyone who is on insulin therapy could benefit from them,” said Dr. Gitelman, who did not disclose any conflicts of interest.

A retrospective study involving 13,809 patients found no evidence that proton pump inhibitors interfere with the antiplatelet drugs clopidogrel and prasugrel in patients with acute cardiac syndrome. Existing guidelines, which endorse the content use of proton pump inhibitors with antiplatelet drugs in these patients, will therefore not need to be changed.

The results contrast with other recent studies suggesting that proton pump inhibitors (PPIs), especially omeprazole, might diminish the drugs' antiplatelet effects and clinical efficacy. The study, which was published online in the Lancet, was presented concurrently by Dr. Michelle L. O'Donoghue at the annual congress of the European Society of Cardiology in Barcelona.

Clopidogrel and prasugrel are in a class of drugs called thienopyridines. They are pro-drugs that are converted by the cytochrome P450 enzyme system into their active metabolites. It was thought that PPIs might interfere with this through their inhibition of a cytochrome P450 isozyme in the liver called 2C19. As a result of these concerns, and of earlier studies that seem to suggest problems, the Food and Drug Administration and the European Medicines Agency (EMEA) issued safety warnings discouraging the use of PPIs with clopidogrel unless absolutely necessary.

The new study involved a retrospective analysis of one large trial involving 13,608 patients and one small trial involving 201 patients. Both were randomized, controlled trials intended to compare clopidogrel with prasugrel in patients undergoing elective percutaneous coronary intervention. In both trials, the use of a PPI was at the discretion of the treating physician. At the time of randomization, 26% of patients in the smaller trial and 33% in the larger trial were taking PPIs.

The investigators, led by Dr. O'Donoghue of Brigham and Women's Hospital, Boston, adjusted their results for 28 potential confounders, including age; sex; ethnic origin; history of hypertension, hypercholesterolemia, heart failure, peptic ulcer disease, carotid or vertebral artery disease, or diabetes; previous MI; previous coronary artery bypass graft surgery (CABG); family history; and the use of a drug-eluting stent (Lancet 2009 [doi:10.1016/S0140-6736(09)61525-7

Although the investigators did find that PPIs were associated with a reduction in the antiplatelet effects of clopidogrel and prasugrel, this did not translate into any significant differences in clinical outcome. There were no significant differences in all cause death, cardiovascular death, MI, stent thrombosis, major or minor bleeding in thrombolysis-induced myocardial infarction, or net clinical outcome (a combination of death, MI, stroke, and major non-CABG bleeding).

In an accompanying editorial, the authors Dr. Dirk Sibbing and Dr. Adnan Kastrati of Technische Universität München (Munich) raised a number of questions. For example, they suggested that patient compliance with thienopyridines might be worse in real life than in the context of the clinical trials. Dr. Sibbing and Dr. Kastrati concluded that PPIs appear not to interact with clopidogrel or prasugrel in terms of clinical outcomes and that patients with a risk profile similar to that in the trials can be safely treated with a PPI (Lancet 2009 [doi:10.1016/S0140-6736(09)61562-2

“However,” they wrote, “caution is needed when prescribing PPIs for selected high-risk patients with an intrinsically reduced response to thienopyridines. … In all cases, careful monitoring of patients' compliance with a thienopyridine drugs is mandatory.”

The original trials received grant funding from Eli Lilly & Co. and from Daiichi Sankyo. The investigators conducting the retrospective analysis stated that they received no external sources of funding.

Dr. Sibbing acknowledged receiving lecture fees from Dynabyte and fees for advisory board activities from Eli Lilly. Dr. Kastrati acknowledged receiving lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly.

Careful monitoring is necessary when patients with reduced response to thienopyridines take PPIs.

Source Dr. Kastrati

A retrospective study involving 13,809 patients found no evidence that proton pump inhibitors interfere with the antiplatelet drugs clopidogrel and prasugrel in patients with acute cardiac syndrome. Existing guidelines, which endorse the content use of proton pump inhibitors with antiplatelet drugs in these patients, will therefore not need to be changed.

The results contrast with other recent studies suggesting that proton pump inhibitors (PPIs), especially omeprazole, might diminish the drugs' antiplatelet effects and clinical efficacy. The study, which was published online in the Lancet, was presented concurrently by Dr. Michelle L. O'Donoghue at the annual congress of the European Society of Cardiology in Barcelona.

Clopidogrel and prasugrel are in a class of drugs called thienopyridines. They are pro-drugs that are converted by the cytochrome P450 enzyme system into their active metabolites. It was thought that PPIs might interfere with this through their inhibition of a cytochrome P450 isozyme in the liver called 2C19. As a result of these concerns, and of earlier studies that seem to suggest problems, the Food and Drug Administration and the European Medicines Agency (EMEA) issued safety warnings discouraging the use of PPIs with clopidogrel unless absolutely necessary.

The new study involved a retrospective analysis of one large trial involving 13,608 patients and one small trial involving 201 patients. Both were randomized, controlled trials intended to compare clopidogrel with prasugrel in patients undergoing elective percutaneous coronary intervention. In both trials, the use of a PPI was at the discretion of the treating physician. At the time of randomization, 26% of patients in the smaller trial and 33% in the larger trial were taking PPIs.

The investigators, led by Dr. O'Donoghue of Brigham and Women's Hospital, Boston, adjusted their results for 28 potential confounders, including age; sex; ethnic origin; history of hypertension, hypercholesterolemia, heart failure, peptic ulcer disease, carotid or vertebral artery disease, or diabetes; previous MI; previous coronary artery bypass graft surgery (CABG); family history; and the use of a drug-eluting stent (Lancet 2009 [doi:10.1016/S0140-6736(09)61525-7

Although the investigators did find that PPIs were associated with a reduction in the antiplatelet effects of clopidogrel and prasugrel, this did not translate into any significant differences in clinical outcome. There were no significant differences in all cause death, cardiovascular death, MI, stent thrombosis, major or minor bleeding in thrombolysis-induced myocardial infarction, or net clinical outcome (a combination of death, MI, stroke, and major non-CABG bleeding).

In an accompanying editorial, the authors Dr. Dirk Sibbing and Dr. Adnan Kastrati of Technische Universität München (Munich) raised a number of questions. For example, they suggested that patient compliance with thienopyridines might be worse in real life than in the context of the clinical trials. Dr. Sibbing and Dr. Kastrati concluded that PPIs appear not to interact with clopidogrel or prasugrel in terms of clinical outcomes and that patients with a risk profile similar to that in the trials can be safely treated with a PPI (Lancet 2009 [doi:10.1016/S0140-6736(09)61562-2

“However,” they wrote, “caution is needed when prescribing PPIs for selected high-risk patients with an intrinsically reduced response to thienopyridines. … In all cases, careful monitoring of patients' compliance with a thienopyridine drugs is mandatory.”

The original trials received grant funding from Eli Lilly & Co. and from Daiichi Sankyo. The investigators conducting the retrospective analysis stated that they received no external sources of funding.

Dr. Sibbing acknowledged receiving lecture fees from Dynabyte and fees for advisory board activities from Eli Lilly. Dr. Kastrati acknowledged receiving lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly.

Careful monitoring is necessary when patients with reduced response to thienopyridines take PPIs.

Source Dr. Kastrati

A retrospective study involving 13,809 patients found no evidence that proton pump inhibitors interfere with the antiplatelet drugs clopidogrel and prasugrel in patients with acute cardiac syndrome. Existing guidelines, which endorse the content use of proton pump inhibitors with antiplatelet drugs in these patients, will therefore not need to be changed.

The results contrast with other recent studies suggesting that proton pump inhibitors (PPIs), especially omeprazole, might diminish the drugs' antiplatelet effects and clinical efficacy. The study, which was published online in the Lancet, was presented concurrently by Dr. Michelle L. O'Donoghue at the annual congress of the European Society of Cardiology in Barcelona.

Clopidogrel and prasugrel are in a class of drugs called thienopyridines. They are pro-drugs that are converted by the cytochrome P450 enzyme system into their active metabolites. It was thought that PPIs might interfere with this through their inhibition of a cytochrome P450 isozyme in the liver called 2C19. As a result of these concerns, and of earlier studies that seem to suggest problems, the Food and Drug Administration and the European Medicines Agency (EMEA) issued safety warnings discouraging the use of PPIs with clopidogrel unless absolutely necessary.

The new study involved a retrospective analysis of one large trial involving 13,608 patients and one small trial involving 201 patients. Both were randomized, controlled trials intended to compare clopidogrel with prasugrel in patients undergoing elective percutaneous coronary intervention. In both trials, the use of a PPI was at the discretion of the treating physician. At the time of randomization, 26% of patients in the smaller trial and 33% in the larger trial were taking PPIs.

The investigators, led by Dr. O'Donoghue of Brigham and Women's Hospital, Boston, adjusted their results for 28 potential confounders, including age; sex; ethnic origin; history of hypertension, hypercholesterolemia, heart failure, peptic ulcer disease, carotid or vertebral artery disease, or diabetes; previous MI; previous coronary artery bypass graft surgery (CABG); family history; and the use of a drug-eluting stent (Lancet 2009 [doi:10.1016/S0140-6736(09)61525-7

Although the investigators did find that PPIs were associated with a reduction in the antiplatelet effects of clopidogrel and prasugrel, this did not translate into any significant differences in clinical outcome. There were no significant differences in all cause death, cardiovascular death, MI, stent thrombosis, major or minor bleeding in thrombolysis-induced myocardial infarction, or net clinical outcome (a combination of death, MI, stroke, and major non-CABG bleeding).

In an accompanying editorial, the authors Dr. Dirk Sibbing and Dr. Adnan Kastrati of Technische Universität München (Munich) raised a number of questions. For example, they suggested that patient compliance with thienopyridines might be worse in real life than in the context of the clinical trials. Dr. Sibbing and Dr. Kastrati concluded that PPIs appear not to interact with clopidogrel or prasugrel in terms of clinical outcomes and that patients with a risk profile similar to that in the trials can be safely treated with a PPI (Lancet 2009 [doi:10.1016/S0140-6736(09)61562-2

“However,” they wrote, “caution is needed when prescribing PPIs for selected high-risk patients with an intrinsically reduced response to thienopyridines. … In all cases, careful monitoring of patients' compliance with a thienopyridine drugs is mandatory.”

The original trials received grant funding from Eli Lilly & Co. and from Daiichi Sankyo. The investigators conducting the retrospective analysis stated that they received no external sources of funding.

Dr. Sibbing acknowledged receiving lecture fees from Dynabyte and fees for advisory board activities from Eli Lilly. Dr. Kastrati acknowledged receiving lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, and Eli Lilly.

Careful monitoring is necessary when patients with reduced response to thienopyridines take PPIs.

Source Dr. Kastrati