Jane Salodof MacNeil

SAN FRANCISCO — Fetal and early natal exposure to antiretroviral therapy may put healthy children of women infected with the HIV at increased risk of heart disease later in life, according a study presented at the annual meeting of the Pediatric Academic Societies.

Dr. Steven E. Lipshultz reported that HIV-negative children born to mothers on antiretroviral therapy (ART) were healthier and had stronger hearts at birth than did HIV-negative children born a decade earlier to infected mothers who were not given ART. During the infants' first year of life, however, echocardiograms showed the ART-exposed children had reductions in left ventricular mass and septal wall thickness, which resulted in “serial increases in left ventricular afterload or stress on the wall of the heart.”

“Initially, there was improved left ventricular contractility and left ventricular fractional shortening,” he said. “What was concerning is there are progressive increases in left ventricular afterload, resulting in the loss of improvement in left ventricular fractional shortening.”

While the clinical significance of these changes is not yet known, they call for much better long-term care of children who escape HIV infection in the womb and are often lost to follow-up because their mothers die or the family is dysfunctional, advised Dr. Lipshultz, chairman of pediatrics at the University of Miami.

“Continued use of antiretroviral therapy to prevent mother-to-child transmission of HIV is critical,” he said, estimating more than a million children have been exposed to ART in utero. “The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity, but [the study] points to the need to really emphasize long-term follow-up in this population.”

The prospective Cardiac Highly Active Antiretroviral Therapy (CHAART) study was sponsored by the National Heart, Lung, and Blood Institute. Dr. Lipshultz said a randomized, controlled trial was not possible, as denying ART to HIV-infected women would be unethical.

Instead, the investigators enrolled participants at the same sites where another NHLBI investigation, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P₂C₂) study, had enrolled HIV-infected mothers from 1990 to 1994. Dr. Lipshultz and his colleagues compared serial echocardiograms for 216 unexposed P₂C₂ infants with those of 91 exposed infants in the CHAART study.

Among their findings was that babies born in the antiretroviral era have better heart function at birth than their predecessors did, but the difference is no longer significant by 6–12 months of age. While left ventricular afterload decreased during the first year of life in the unexposed infants, it increased in those whose mothers received ART.

“Initially, there was less stress on the heart, but with time, this really flipped, and there was about half a standard deviation more stress/higher afterload by a year of age. And that was significant,” Dr. Lipshultz said. He reported the difference in septal wall thickness was more than a standard deviation at all ages.

“We speculate that antiretroviral exposure appears to be associated with reduced myocardiac growth that may be putting these children at greater risk for subsequent cardiac problems,” Dr. Lipshultz said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

“In many cases, [ART-exposed children] get lost from the regular medical system,” he said. Because of limited resources, only children who are born HIV positive are apt to receive comprehensive follow-up at pediatric HIV clinics. So care of HIV-negative offspring falls to the primary care physician, he said.

'The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity.' DR. LIPSHULTZ

SAN FRANCISCO — Fetal and early natal exposure to antiretroviral therapy may put healthy children of women infected with the HIV at increased risk of heart disease later in life, according a study presented at the annual meeting of the Pediatric Academic Societies.

Dr. Steven E. Lipshultz reported that HIV-negative children born to mothers on antiretroviral therapy (ART) were healthier and had stronger hearts at birth than did HIV-negative children born a decade earlier to infected mothers who were not given ART. During the infants' first year of life, however, echocardiograms showed the ART-exposed children had reductions in left ventricular mass and septal wall thickness, which resulted in “serial increases in left ventricular afterload or stress on the wall of the heart.”

“Initially, there was improved left ventricular contractility and left ventricular fractional shortening,” he said. “What was concerning is there are progressive increases in left ventricular afterload, resulting in the loss of improvement in left ventricular fractional shortening.”

While the clinical significance of these changes is not yet known, they call for much better long-term care of children who escape HIV infection in the womb and are often lost to follow-up because their mothers die or the family is dysfunctional, advised Dr. Lipshultz, chairman of pediatrics at the University of Miami.

“Continued use of antiretroviral therapy to prevent mother-to-child transmission of HIV is critical,” he said, estimating more than a million children have been exposed to ART in utero. “The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity, but [the study] points to the need to really emphasize long-term follow-up in this population.”

The prospective Cardiac Highly Active Antiretroviral Therapy (CHAART) study was sponsored by the National Heart, Lung, and Blood Institute. Dr. Lipshultz said a randomized, controlled trial was not possible, as denying ART to HIV-infected women would be unethical.

Instead, the investigators enrolled participants at the same sites where another NHLBI investigation, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P₂C₂) study, had enrolled HIV-infected mothers from 1990 to 1994. Dr. Lipshultz and his colleagues compared serial echocardiograms for 216 unexposed P₂C₂ infants with those of 91 exposed infants in the CHAART study.

Among their findings was that babies born in the antiretroviral era have better heart function at birth than their predecessors did, but the difference is no longer significant by 6–12 months of age. While left ventricular afterload decreased during the first year of life in the unexposed infants, it increased in those whose mothers received ART.

“Initially, there was less stress on the heart, but with time, this really flipped, and there was about half a standard deviation more stress/higher afterload by a year of age. And that was significant,” Dr. Lipshultz said. He reported the difference in septal wall thickness was more than a standard deviation at all ages.

“We speculate that antiretroviral exposure appears to be associated with reduced myocardiac growth that may be putting these children at greater risk for subsequent cardiac problems,” Dr. Lipshultz said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

“In many cases, [ART-exposed children] get lost from the regular medical system,” he said. Because of limited resources, only children who are born HIV positive are apt to receive comprehensive follow-up at pediatric HIV clinics. So care of HIV-negative offspring falls to the primary care physician, he said.

'The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity.' DR. LIPSHULTZ

SAN FRANCISCO — Fetal and early natal exposure to antiretroviral therapy may put healthy children of women infected with the HIV at increased risk of heart disease later in life, according a study presented at the annual meeting of the Pediatric Academic Societies.

Dr. Steven E. Lipshultz reported that HIV-negative children born to mothers on antiretroviral therapy (ART) were healthier and had stronger hearts at birth than did HIV-negative children born a decade earlier to infected mothers who were not given ART. During the infants' first year of life, however, echocardiograms showed the ART-exposed children had reductions in left ventricular mass and septal wall thickness, which resulted in “serial increases in left ventricular afterload or stress on the wall of the heart.”

“Initially, there was improved left ventricular contractility and left ventricular fractional shortening,” he said. “What was concerning is there are progressive increases in left ventricular afterload, resulting in the loss of improvement in left ventricular fractional shortening.”

While the clinical significance of these changes is not yet known, they call for much better long-term care of children who escape HIV infection in the womb and are often lost to follow-up because their mothers die or the family is dysfunctional, advised Dr. Lipshultz, chairman of pediatrics at the University of Miami.

“Continued use of antiretroviral therapy to prevent mother-to-child transmission of HIV is critical,” he said, estimating more than a million children have been exposed to ART in utero. “The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity, but [the study] points to the need to really emphasize long-term follow-up in this population.”

The prospective Cardiac Highly Active Antiretroviral Therapy (CHAART) study was sponsored by the National Heart, Lung, and Blood Institute. Dr. Lipshultz said a randomized, controlled trial was not possible, as denying ART to HIV-infected women would be unethical.

Instead, the investigators enrolled participants at the same sites where another NHLBI investigation, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P₂C₂) study, had enrolled HIV-infected mothers from 1990 to 1994. Dr. Lipshultz and his colleagues compared serial echocardiograms for 216 unexposed P₂C₂ infants with those of 91 exposed infants in the CHAART study.

Among their findings was that babies born in the antiretroviral era have better heart function at birth than their predecessors did, but the difference is no longer significant by 6–12 months of age. While left ventricular afterload decreased during the first year of life in the unexposed infants, it increased in those whose mothers received ART.

“Initially, there was less stress on the heart, but with time, this really flipped, and there was about half a standard deviation more stress/higher afterload by a year of age. And that was significant,” Dr. Lipshultz said. He reported the difference in septal wall thickness was more than a standard deviation at all ages.

“We speculate that antiretroviral exposure appears to be associated with reduced myocardiac growth that may be putting these children at greater risk for subsequent cardiac problems,” Dr. Lipshultz said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

“In many cases, [ART-exposed children] get lost from the regular medical system,” he said. Because of limited resources, only children who are born HIV positive are apt to receive comprehensive follow-up at pediatric HIV clinics. So care of HIV-negative offspring falls to the primary care physician, he said.

'The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity.' DR. LIPSHULTZ

SAN FRANCISCO – Preteens and adolescents with asthma who were also depressed or anxious had asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Based on these findings, the investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (795 vs. 581).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

The respondents with anxiety or depressive disorders also were significantly more likely than the other respondents to report each of six asthma-specific symptoms (wheezing with a cold, cold that won't go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview before her presentation at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Providersshould consider screening for depression' if kids are not responding to treatment. DR. RICHARDSON

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO – Preteens and adolescents with asthma who were also depressed or anxious had asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Based on these findings, the investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (795 vs. 581).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

The respondents with anxiety or depressive disorders also were significantly more likely than the other respondents to report each of six asthma-specific symptoms (wheezing with a cold, cold that won't go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview before her presentation at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Providersshould consider screening for depression' if kids are not responding to treatment. DR. RICHARDSON

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO – Preteens and adolescents with asthma who were also depressed or anxious had asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Based on these findings, the investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (795 vs. 581).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

The respondents with anxiety or depressive disorders also were significantly more likely than the other respondents to report each of six asthma-specific symptoms (wheezing with a cold, cold that won't go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview before her presentation at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Providersshould consider screening for depression' if kids are not responding to treatment. DR. RICHARDSON

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Community-acquired pneumonia patients are significantly more likely to die within 3 months of leaving the hospital if they have high concentrations of inflammatory cytokines before discharge, Dr. Sachin Yende reported at the international conference of the American Thoracic Society.

Above-normal levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were strongly associated with 90-day mortality in a large, ongoing study presented by Dr. Yende of the University of Pittsburgh Medical Center.

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days: 10.6 pg/mL vs. 5.9 pg/mL in survivors. IL-10 levels were three times as high in the patients who died: 3.1 pg/mL vs. 1 pg/mL.

Concentrations of both cytokines were slightly higher in patients who had had sepsis while hospitalized but not significantly higher than the levels measured near discharge in those who had not had sepsis.

“People are sent home with fairly high cytokine concentrations,” Dr. Yende said in an interview.

“If physicians were aware, they would not have wanted to send these patients home.” The physicians were not aware, he said, because cytokine levels are not routinely ordered and the study was blinded.

The investigation follows an earlier finding that recovered community-acquired pneumonia patients have higher mortality 5 years after hospitalization than would be predicted by their age, gender, or other variables. “The increased mortality we have seen is not because these people are older or have more chronic health conditions. It is because of this hospitalization,” Dr. Yende said, adding that he and his colleagues were trying to find out why.

The cohort study collected blood daily for 1 week and once weekly subsequently, starting with 2,320 patients who presented with pneumonia in the emergency departments at 28 hospitals. Of 1,895 patients who were admitted, 87 (5%) died in the hospital.

Among the remaining patients, 1,799 were alive at discharge and included in the cohort followed by investigators, but 126 (7%) of these patients died within 90 days. Dr. Yende reported 1,636 were still alive, and outcomes were not known for 37 (2%) of the discharged patients.

The IL-6 and IL-10 data were based on 1,452 patients in whom concentrations were measured 48 hours before discharge. Overall, the median IL-6 and IL-10 levels as measured between the 10th and 90th percentiles were 6.2 pg/mL and 5 pg/mL, respectively. In comparison, Dr. Yende said, median IL-6 levels typically range from 1.8 pg/mL in healthy persons to 98.7 pg/mL in patients with severe sepsis.

While Dr. Yende emphasized that more work needs to be done before the investigators can establish causality, he speculated that an acute illness such as pneumonia might be a “feed-forward phenomenon” that leads to increased incidence of pneumonia or cardiovascular events.

“An acute event like pneumonia or sepsis may alter subsequent life trajectory even after hospital discharge,” he said.

The investigators obtained 1-year data on the discharged pneumonia patients shortly before Dr. Yende's presentation. Though they had not had time for a full analysis, he reported mortality had reached 16%. The five leading causes of death at 1 year were chronic ischemic heart disease, malignant neoplasms of the respiratory system, pneumonia, cerebrovascular disease, and acute myocardial infarction.

“These are the same diseases that have been shown in cardiovascular literature to be associated with increased risk when you have elevated C-reactive protein and other inflammatory markers,” Dr. Yende said.

At this point, he said, a recommendation for routine measurement of inflammatory markers would be premature. In the future, he predicted, this could become standard along with interventions and a faster follow-up visit in the physician's office.

“Normally you say [to] come back after 6 weeks,” he said. “Maybe there is a role to call them back earlier and remeasure and see how things go—but right now, there isn't evidence to support that.”

Asked whether pressure to send pneumonia patients home faster could be a factor, Dr. Yende said the vast majority of discharged patients are ready to go home. “They are on the road to recovery,” he said. “And that is the interesting point. Even if you think they are ready to go home, perhaps there is something going on that may be completely bad.”

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days. DR. YENDE

SAN DIEGO — Community-acquired pneumonia patients are significantly more likely to die within 3 months of leaving the hospital if they have high concentrations of inflammatory cytokines before discharge, Dr. Sachin Yende reported at the international conference of the American Thoracic Society.

Above-normal levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were strongly associated with 90-day mortality in a large, ongoing study presented by Dr. Yende of the University of Pittsburgh Medical Center.

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days: 10.6 pg/mL vs. 5.9 pg/mL in survivors. IL-10 levels were three times as high in the patients who died: 3.1 pg/mL vs. 1 pg/mL.

Concentrations of both cytokines were slightly higher in patients who had had sepsis while hospitalized but not significantly higher than the levels measured near discharge in those who had not had sepsis.

“People are sent home with fairly high cytokine concentrations,” Dr. Yende said in an interview.

“If physicians were aware, they would not have wanted to send these patients home.” The physicians were not aware, he said, because cytokine levels are not routinely ordered and the study was blinded.

The investigation follows an earlier finding that recovered community-acquired pneumonia patients have higher mortality 5 years after hospitalization than would be predicted by their age, gender, or other variables. “The increased mortality we have seen is not because these people are older or have more chronic health conditions. It is because of this hospitalization,” Dr. Yende said, adding that he and his colleagues were trying to find out why.

The cohort study collected blood daily for 1 week and once weekly subsequently, starting with 2,320 patients who presented with pneumonia in the emergency departments at 28 hospitals. Of 1,895 patients who were admitted, 87 (5%) died in the hospital.

Among the remaining patients, 1,799 were alive at discharge and included in the cohort followed by investigators, but 126 (7%) of these patients died within 90 days. Dr. Yende reported 1,636 were still alive, and outcomes were not known for 37 (2%) of the discharged patients.

The IL-6 and IL-10 data were based on 1,452 patients in whom concentrations were measured 48 hours before discharge. Overall, the median IL-6 and IL-10 levels as measured between the 10th and 90th percentiles were 6.2 pg/mL and 5 pg/mL, respectively. In comparison, Dr. Yende said, median IL-6 levels typically range from 1.8 pg/mL in healthy persons to 98.7 pg/mL in patients with severe sepsis.

While Dr. Yende emphasized that more work needs to be done before the investigators can establish causality, he speculated that an acute illness such as pneumonia might be a “feed-forward phenomenon” that leads to increased incidence of pneumonia or cardiovascular events.

“An acute event like pneumonia or sepsis may alter subsequent life trajectory even after hospital discharge,” he said.

The investigators obtained 1-year data on the discharged pneumonia patients shortly before Dr. Yende's presentation. Though they had not had time for a full analysis, he reported mortality had reached 16%. The five leading causes of death at 1 year were chronic ischemic heart disease, malignant neoplasms of the respiratory system, pneumonia, cerebrovascular disease, and acute myocardial infarction.

“These are the same diseases that have been shown in cardiovascular literature to be associated with increased risk when you have elevated C-reactive protein and other inflammatory markers,” Dr. Yende said.

At this point, he said, a recommendation for routine measurement of inflammatory markers would be premature. In the future, he predicted, this could become standard along with interventions and a faster follow-up visit in the physician's office.

“Normally you say [to] come back after 6 weeks,” he said. “Maybe there is a role to call them back earlier and remeasure and see how things go—but right now, there isn't evidence to support that.”

Asked whether pressure to send pneumonia patients home faster could be a factor, Dr. Yende said the vast majority of discharged patients are ready to go home. “They are on the road to recovery,” he said. “And that is the interesting point. Even if you think they are ready to go home, perhaps there is something going on that may be completely bad.”

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days. DR. YENDE

SAN DIEGO — Community-acquired pneumonia patients are significantly more likely to die within 3 months of leaving the hospital if they have high concentrations of inflammatory cytokines before discharge, Dr. Sachin Yende reported at the international conference of the American Thoracic Society.

Above-normal levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were strongly associated with 90-day mortality in a large, ongoing study presented by Dr. Yende of the University of Pittsburgh Medical Center.

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days: 10.6 pg/mL vs. 5.9 pg/mL in survivors. IL-10 levels were three times as high in the patients who died: 3.1 pg/mL vs. 1 pg/mL.

Concentrations of both cytokines were slightly higher in patients who had had sepsis while hospitalized but not significantly higher than the levels measured near discharge in those who had not had sepsis.

“People are sent home with fairly high cytokine concentrations,” Dr. Yende said in an interview.

“If physicians were aware, they would not have wanted to send these patients home.” The physicians were not aware, he said, because cytokine levels are not routinely ordered and the study was blinded.

The investigation follows an earlier finding that recovered community-acquired pneumonia patients have higher mortality 5 years after hospitalization than would be predicted by their age, gender, or other variables. “The increased mortality we have seen is not because these people are older or have more chronic health conditions. It is because of this hospitalization,” Dr. Yende said, adding that he and his colleagues were trying to find out why.

The cohort study collected blood daily for 1 week and once weekly subsequently, starting with 2,320 patients who presented with pneumonia in the emergency departments at 28 hospitals. Of 1,895 patients who were admitted, 87 (5%) died in the hospital.

Among the remaining patients, 1,799 were alive at discharge and included in the cohort followed by investigators, but 126 (7%) of these patients died within 90 days. Dr. Yende reported 1,636 were still alive, and outcomes were not known for 37 (2%) of the discharged patients.

The IL-6 and IL-10 data were based on 1,452 patients in whom concentrations were measured 48 hours before discharge. Overall, the median IL-6 and IL-10 levels as measured between the 10th and 90th percentiles were 6.2 pg/mL and 5 pg/mL, respectively. In comparison, Dr. Yende said, median IL-6 levels typically range from 1.8 pg/mL in healthy persons to 98.7 pg/mL in patients with severe sepsis.

While Dr. Yende emphasized that more work needs to be done before the investigators can establish causality, he speculated that an acute illness such as pneumonia might be a “feed-forward phenomenon” that leads to increased incidence of pneumonia or cardiovascular events.

“An acute event like pneumonia or sepsis may alter subsequent life trajectory even after hospital discharge,” he said.

The investigators obtained 1-year data on the discharged pneumonia patients shortly before Dr. Yende's presentation. Though they had not had time for a full analysis, he reported mortality had reached 16%. The five leading causes of death at 1 year were chronic ischemic heart disease, malignant neoplasms of the respiratory system, pneumonia, cerebrovascular disease, and acute myocardial infarction.

“These are the same diseases that have been shown in cardiovascular literature to be associated with increased risk when you have elevated C-reactive protein and other inflammatory markers,” Dr. Yende said.

At this point, he said, a recommendation for routine measurement of inflammatory markers would be premature. In the future, he predicted, this could become standard along with interventions and a faster follow-up visit in the physician's office.

“Normally you say [to] come back after 6 weeks,” he said. “Maybe there is a role to call them back earlier and remeasure and see how things go—but right now, there isn't evidence to support that.”

Asked whether pressure to send pneumonia patients home faster could be a factor, Dr. Yende said the vast majority of discharged patients are ready to go home. “They are on the road to recovery,” he said. “And that is the interesting point. Even if you think they are ready to go home, perhaps there is something going on that may be completely bad.”

Predischarge IL-6 concentrations were nearly twice as high in discharged patients who died within 90 days. DR. YENDE

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology.

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution. Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen.

“We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster, where he was joined by the lead author, Dr. Mariangela Ciccarese. “We found there is a benefit in survival when you pool all the results.”

The pooled analysis only addressed an early-switch strategy, as Dr. Bria said he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. He said he hopes to pool additional studies and compare early, up-front, and late strategies when more trials become available.

The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366: 455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group. The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22.

In looking for the effect of the whole class of drugs, 'we found there is a benefit in survival when you pool all the results.' DR. BRIA

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology.

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution. Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen.

“We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster, where he was joined by the lead author, Dr. Mariangela Ciccarese. “We found there is a benefit in survival when you pool all the results.”

The pooled analysis only addressed an early-switch strategy, as Dr. Bria said he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. He said he hopes to pool additional studies and compare early, up-front, and late strategies when more trials become available.

The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366: 455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group. The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22.

In looking for the effect of the whole class of drugs, 'we found there is a benefit in survival when you pool all the results.' DR. BRIA

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology.

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution. Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen.

“We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster, where he was joined by the lead author, Dr. Mariangela Ciccarese. “We found there is a benefit in survival when you pool all the results.”

The pooled analysis only addressed an early-switch strategy, as Dr. Bria said he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. He said he hopes to pool additional studies and compare early, up-front, and late strategies when more trials become available.

The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366: 455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group. The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22.

In looking for the effect of the whole class of drugs, 'we found there is a benefit in survival when you pool all the results.' DR. BRIA

ATLANTA — High-dose isoflavone soy supplements failed to control the hot flashes of breast cancer survivors in a randomized controlled trial presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Although the crossover trial was halted midway for failing to show benefit, 82% of participants reduced their hot flashes during the first 4 weeks of the study. The key to their success, Dr. William C. Dooley reported, apparently was an online Internet journal that all the women filled out each day.

“Most patients, whether they started on soy or placebo, came up with triggers for hot flashes that they could avoid and decrease the frequency,” Dr. Dooley, chair of surgical breast oncology at the University of Oklahoma in Oklahoma City, said in an interview at the meeting.

“They were writing that in their journals and after the first month the hot flashes had dropped over 30% and the severity dropped dramatically just by avoidance of diet, emotion, or other triggers,” he said. “There was no difference between the soy and placebo.”

Dr. Dooley and his coinvestigators enrolled 168 breast cancer survivors for what was to be a 16-week crossover trial. All were suffering from hot flashes and had progressed at least 6 weeks beyond completion of surgery, chemotherapy, or radiation. Patients on tamoxifen or another adjuvant hormonal therapy were allowed.

The double-blind design called for all women to participate in a 4-hour-per-week exercise program and take two dietary supplements, one of which contained 130 mg of isoflavone soy. Dr. Dooley said the dose was comparable with the amount of soy in the Japanese diet and much higher than is usually studied in randomized trials.

Of the original 168 enrollees, 51 dropped out either because they failed to complete the exercise requirement or because the physicians managing their care had objections. Another 13 participants stopped using the supplements. The usual reason was gas and/or gastrointestinal distress from the soy supplement or the casein placebo. This left 104 evaluable patients in the analysis.

Dr. Dooley said the journal component was added to the trial by breast cancer survivors who “wanted to share more information than multiple choice answers when it was over.”

Patients recorded hot flash frequency, severity, and time of day as well as exercise time in Internet diaries, which they accessed by password on a server compliant with the Health Insurance Portability and Accountability Act.

This turned out to be the most interesting part of the study, according to Dr. Dooley. “There is some benefit of journaling, so they will learn to avoid hot flashes,” he said.

Although the investigators did not find soy to provide any benefit in symptom control, Dr. Dooley said they have not ruled out other advantages.

“We did not look at cholesterol, bone density, or heart disease. … Those are some things we are going to look at in future,” he said, adding that his group is assessing soy's impact on atypical hyperplasia in another ongoing trial.

ATLANTA — High-dose isoflavone soy supplements failed to control the hot flashes of breast cancer survivors in a randomized controlled trial presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Although the crossover trial was halted midway for failing to show benefit, 82% of participants reduced their hot flashes during the first 4 weeks of the study. The key to their success, Dr. William C. Dooley reported, apparently was an online Internet journal that all the women filled out each day.

“Most patients, whether they started on soy or placebo, came up with triggers for hot flashes that they could avoid and decrease the frequency,” Dr. Dooley, chair of surgical breast oncology at the University of Oklahoma in Oklahoma City, said in an interview at the meeting.

“They were writing that in their journals and after the first month the hot flashes had dropped over 30% and the severity dropped dramatically just by avoidance of diet, emotion, or other triggers,” he said. “There was no difference between the soy and placebo.”

Dr. Dooley and his coinvestigators enrolled 168 breast cancer survivors for what was to be a 16-week crossover trial. All were suffering from hot flashes and had progressed at least 6 weeks beyond completion of surgery, chemotherapy, or radiation. Patients on tamoxifen or another adjuvant hormonal therapy were allowed.

The double-blind design called for all women to participate in a 4-hour-per-week exercise program and take two dietary supplements, one of which contained 130 mg of isoflavone soy. Dr. Dooley said the dose was comparable with the amount of soy in the Japanese diet and much higher than is usually studied in randomized trials.

Of the original 168 enrollees, 51 dropped out either because they failed to complete the exercise requirement or because the physicians managing their care had objections. Another 13 participants stopped using the supplements. The usual reason was gas and/or gastrointestinal distress from the soy supplement or the casein placebo. This left 104 evaluable patients in the analysis.

Dr. Dooley said the journal component was added to the trial by breast cancer survivors who “wanted to share more information than multiple choice answers when it was over.”

Patients recorded hot flash frequency, severity, and time of day as well as exercise time in Internet diaries, which they accessed by password on a server compliant with the Health Insurance Portability and Accountability Act.

This turned out to be the most interesting part of the study, according to Dr. Dooley. “There is some benefit of journaling, so they will learn to avoid hot flashes,” he said.

Although the investigators did not find soy to provide any benefit in symptom control, Dr. Dooley said they have not ruled out other advantages.

“We did not look at cholesterol, bone density, or heart disease. … Those are some things we are going to look at in future,” he said, adding that his group is assessing soy's impact on atypical hyperplasia in another ongoing trial.

ATLANTA — High-dose isoflavone soy supplements failed to control the hot flashes of breast cancer survivors in a randomized controlled trial presented in a poster at the annual meeting of the American Society of Clinical Oncology.

Although the crossover trial was halted midway for failing to show benefit, 82% of participants reduced their hot flashes during the first 4 weeks of the study. The key to their success, Dr. William C. Dooley reported, apparently was an online Internet journal that all the women filled out each day.

“Most patients, whether they started on soy or placebo, came up with triggers for hot flashes that they could avoid and decrease the frequency,” Dr. Dooley, chair of surgical breast oncology at the University of Oklahoma in Oklahoma City, said in an interview at the meeting.

“They were writing that in their journals and after the first month the hot flashes had dropped over 30% and the severity dropped dramatically just by avoidance of diet, emotion, or other triggers,” he said. “There was no difference between the soy and placebo.”

Dr. Dooley and his coinvestigators enrolled 168 breast cancer survivors for what was to be a 16-week crossover trial. All were suffering from hot flashes and had progressed at least 6 weeks beyond completion of surgery, chemotherapy, or radiation. Patients on tamoxifen or another adjuvant hormonal therapy were allowed.

The double-blind design called for all women to participate in a 4-hour-per-week exercise program and take two dietary supplements, one of which contained 130 mg of isoflavone soy. Dr. Dooley said the dose was comparable with the amount of soy in the Japanese diet and much higher than is usually studied in randomized trials.

Of the original 168 enrollees, 51 dropped out either because they failed to complete the exercise requirement or because the physicians managing their care had objections. Another 13 participants stopped using the supplements. The usual reason was gas and/or gastrointestinal distress from the soy supplement or the casein placebo. This left 104 evaluable patients in the analysis.

Dr. Dooley said the journal component was added to the trial by breast cancer survivors who “wanted to share more information than multiple choice answers when it was over.”

Patients recorded hot flash frequency, severity, and time of day as well as exercise time in Internet diaries, which they accessed by password on a server compliant with the Health Insurance Portability and Accountability Act.

This turned out to be the most interesting part of the study, according to Dr. Dooley. “There is some benefit of journaling, so they will learn to avoid hot flashes,” he said.

Although the investigators did not find soy to provide any benefit in symptom control, Dr. Dooley said they have not ruled out other advantages.

“We did not look at cholesterol, bone density, or heart disease. … Those are some things we are going to look at in future,” he said, adding that his group is assessing soy's impact on atypical hyperplasia in another ongoing trial.

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology,

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution.

Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen. “We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster.

The pooled analysis only addressed an early-switch strategy because, Dr. Bria said, he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366:455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology,

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution.

Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen. “We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster.

The pooled analysis only addressed an early-switch strategy because, Dr. Bria said, he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366:455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA

ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology,

Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.

Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution.

Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen. “We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster.

The pooled analysis only addressed an early-switch strategy because, Dr. Bria said, he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366:455–62).

Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.

Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA

SAN DIEGO — Newborns who come home to a family cat may be at greater risk of developing eczema by their first birthday, according to an ongoing, prospective birth cohort study presented at the International Conference of the American Thoracic Society.

Dr. Esmeralda Morales reported 28% of 134 infants with household cats developed eczema by 1 year of age. The skin condition appeared in only 18% of 286 infants raised without cats. The difference was statistically significant with an odds ratio of 1.75 that early exposure to cats would lead to eczema. The effect was stronger for babies whose mothers did not have asthma.

Dr. Morales, of the University of Arizona in Tucson, said the finding was a surprise to the researchers. They had hypothesized that early pet exposure would be associated with less risk of wheeze, eczema, and rhinitis apart from colds.

Dogs fared better in the analysis from the Infant Immune Study. More families had dogs: 341 had fewer than two indoor dogs, and 80 had two or more.

Infants exposed to two or more indoor dogs from birth were significantly less likely to develop wheeze by age 1 year (OR 0.53). If the family kept any dog indoors, the risk of rhinitis at 1 year also was significantly less (OR 0.50). There was no significant effect of indoor dog ownership on eczema.

The investigators plan to do a longitudinal analysis to determine whether the infants that develop eczema also are more likely to develop allergic conditions such as asthma and hay fever.

The difference was statistically significant with an OR of 1.75 that early exposure to cats would lead to eczema. DR. MORALES

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Newborns who come home to a family cat may be at greater risk of developing eczema by their first birthday, according to an ongoing, prospective birth cohort study presented at the International Conference of the American Thoracic Society.

Dr. Esmeralda Morales reported 28% of 134 infants with household cats developed eczema by 1 year of age. The skin condition appeared in only 18% of 286 infants raised without cats. The difference was statistically significant with an odds ratio of 1.75 that early exposure to cats would lead to eczema. The effect was stronger for babies whose mothers did not have asthma.

Dr. Morales, of the University of Arizona in Tucson, said the finding was a surprise to the researchers. They had hypothesized that early pet exposure would be associated with less risk of wheeze, eczema, and rhinitis apart from colds.

Dogs fared better in the analysis from the Infant Immune Study. More families had dogs: 341 had fewer than two indoor dogs, and 80 had two or more.

Infants exposed to two or more indoor dogs from birth were significantly less likely to develop wheeze by age 1 year (OR 0.53). If the family kept any dog indoors, the risk of rhinitis at 1 year also was significantly less (OR 0.50). There was no significant effect of indoor dog ownership on eczema.

The investigators plan to do a longitudinal analysis to determine whether the infants that develop eczema also are more likely to develop allergic conditions such as asthma and hay fever.

The difference was statistically significant with an OR of 1.75 that early exposure to cats would lead to eczema. DR. MORALES

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Newborns who come home to a family cat may be at greater risk of developing eczema by their first birthday, according to an ongoing, prospective birth cohort study presented at the International Conference of the American Thoracic Society.

Dr. Esmeralda Morales reported 28% of 134 infants with household cats developed eczema by 1 year of age. The skin condition appeared in only 18% of 286 infants raised without cats. The difference was statistically significant with an odds ratio of 1.75 that early exposure to cats would lead to eczema. The effect was stronger for babies whose mothers did not have asthma.

Dr. Morales, of the University of Arizona in Tucson, said the finding was a surprise to the researchers. They had hypothesized that early pet exposure would be associated with less risk of wheeze, eczema, and rhinitis apart from colds.

Dogs fared better in the analysis from the Infant Immune Study. More families had dogs: 341 had fewer than two indoor dogs, and 80 had two or more.

Infants exposed to two or more indoor dogs from birth were significantly less likely to develop wheeze by age 1 year (OR 0.53). If the family kept any dog indoors, the risk of rhinitis at 1 year also was significantly less (OR 0.50). There was no significant effect of indoor dog ownership on eczema.

The investigators plan to do a longitudinal analysis to determine whether the infants that develop eczema also are more likely to develop allergic conditions such as asthma and hay fever.

The difference was statistically significant with an OR of 1.75 that early exposure to cats would lead to eczema. DR. MORALES

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years.

No deaths occurred in the youngest group after switch therapy, and mortality was low among the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy. “Even if they are over 90 they can, more or less,” he said in an interview.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge once they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day, and in the youngest group, 57.1% passed this goal by the 4th day.

All told, the proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest patients. The proportion of patients who were switched was similar across groups, however: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of IV antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, vs. 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

Older patients often have comorbidities that present a barrier to switch therapy but also put them at risk of nosocomial infection if they stay in the hospital, Dr. Rossi said. Hence, as stated on the poster, “for these patients an early discharge is potentially more important than in younger patients.”

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years.

No deaths occurred in the youngest group after switch therapy, and mortality was low among the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy. “Even if they are over 90 they can, more or less,” he said in an interview.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge once they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day, and in the youngest group, 57.1% passed this goal by the 4th day.

All told, the proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest patients. The proportion of patients who were switched was similar across groups, however: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of IV antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, vs. 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

Older patients often have comorbidities that present a barrier to switch therapy but also put them at risk of nosocomial infection if they stay in the hospital, Dr. Rossi said. Hence, as stated on the poster, “for these patients an early discharge is potentially more important than in younger patients.”

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years.

No deaths occurred in the youngest group after switch therapy, and mortality was low among the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy. “Even if they are over 90 they can, more or less,” he said in an interview.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge once they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day, and in the youngest group, 57.1% passed this goal by the 4th day.

All told, the proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest patients. The proportion of patients who were switched was similar across groups, however: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of IV antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, vs. 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

Older patients often have comorbidities that present a barrier to switch therapy but also put them at risk of nosocomial infection if they stay in the hospital, Dr. Rossi said. Hence, as stated on the poster, “for these patients an early discharge is potentially more important than in younger patients.”

Women taking valproate for bipolar disorder are at significantly increased risk of developing features of polycystic ovary syndrome, according to a published study of 230 female patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial.

Investigators reported finding new-onset oligomenorrhea with hyperandrogenism in 9 (10.5%) of 86 women treated with valproate (Biol. Psychiatry 2006;59:1078–86).

Only 2 (1.4%) of 144 women on lithium or an anticonvulsant other than valproate developed these symptoms of polycystic ovary syndrome (PCOS).

In all cases, oligomenorrhea began within a year of the patient's starting valproate use. The investigators calculated the relative risk as 7.5 for women with bipolar disorder using valproate as a mood stabilizer.

Dr. Hadine Joffe, the lead author, is director of endocrine studies in the perinatal and reproductive psychiatry clinical research program at Massachusetts General Hospital in Boston.

She and her colleagues recommended warning women of PCOS risk before starting them on valproate.

Further, women on valproate should be evaluated for PCOS if they develop menstrual irregularities with hyperandrogenic symptoms. Along with PCOS treatment, the investigators suggested that “it may also be appropriate to consider alternative mood stabilizers if PCOS features develop on valproate.”

In an address at a psychiatric symposium sponsored by the University of Arizona, Dr. Gary Sachs, senior author and principal investigator of STEP-BD, emphasized the need for vigilance during the first year a patient is on valproate.

“Before you start women on valproate, you absolutely have to warn them this is a risk,” Dr. Sachs, founder and director of the bipolar clinic and research program at Massachusetts General Hospital, told psychiatrists at the Santa Fe, N.M., symposium, which was also sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Sponsored by the National Institute of Mental Health, STEP-BD enrolled 4,361 patients in the largest clinical study to date on the treatment of bipolar disorder. Dr. Sachs said that Abbott Laboratories, which sells valproate under the brand name Depakote, was among the drug companies that supported the trial.

“They were very confident the risk wasn't there,” he said. “It turned out that was wrong. There really was a risk. The risks are there and published.”

To study the relationship in a nonepileptic population, the investigators sought out women aged 18–45 years in STEP-BD who were taking at least one mood stabilizer for at least 3 months.

Participants who had discontinued another mood stabilizer within the previous 3 months were not included in the substudy.

Of the 300 identified eligible women, 14 patients previously diagnosed with PCOS and three others with disorders involving oligomenorrhea were among those excluded from the sample. All told, 230 women were available for the analysis.

Of the valproate users, 12 developed oligomenorrhea, and 9 of them also had hirsutism, according to the report.

Among all patients with oligomenorrhea, valproate users had fewer menstrual cycles (median of 5 vs. 8.5 per year) than did nonusers.

Some had elevated total or free testosterone, moderate to severe acne, or male-pattern alopecia.

The valproate users who developed oligomenorrhea with hyperandrogenism had a higher median body mass index (kg/m

“Our study raises the possibility that increased body weight, insulin resistance, PCO morphology, younger age of first valproate use, and polypharmacy may predispose to the development of PCOS features on valproate,” the investigators concluded.

Women taking valproate for bipolar disorder are at significantly increased risk of developing features of polycystic ovary syndrome, according to a published study of 230 female patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial.

Investigators reported finding new-onset oligomenorrhea with hyperandrogenism in 9 (10.5%) of 86 women treated with valproate (Biol. Psychiatry 2006;59:1078–86).

Only 2 (1.4%) of 144 women on lithium or an anticonvulsant other than valproate developed these symptoms of polycystic ovary syndrome (PCOS).

In all cases, oligomenorrhea began within a year of the patient's starting valproate use. The investigators calculated the relative risk as 7.5 for women with bipolar disorder using valproate as a mood stabilizer.

Dr. Hadine Joffe, the lead author, is director of endocrine studies in the perinatal and reproductive psychiatry clinical research program at Massachusetts General Hospital in Boston.

She and her colleagues recommended warning women of PCOS risk before starting them on valproate.

Further, women on valproate should be evaluated for PCOS if they develop menstrual irregularities with hyperandrogenic symptoms. Along with PCOS treatment, the investigators suggested that “it may also be appropriate to consider alternative mood stabilizers if PCOS features develop on valproate.”

In an address at a psychiatric symposium sponsored by the University of Arizona, Dr. Gary Sachs, senior author and principal investigator of STEP-BD, emphasized the need for vigilance during the first year a patient is on valproate.

“Before you start women on valproate, you absolutely have to warn them this is a risk,” Dr. Sachs, founder and director of the bipolar clinic and research program at Massachusetts General Hospital, told psychiatrists at the Santa Fe, N.M., symposium, which was also sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Sponsored by the National Institute of Mental Health, STEP-BD enrolled 4,361 patients in the largest clinical study to date on the treatment of bipolar disorder. Dr. Sachs said that Abbott Laboratories, which sells valproate under the brand name Depakote, was among the drug companies that supported the trial.

“They were very confident the risk wasn't there,” he said. “It turned out that was wrong. There really was a risk. The risks are there and published.”

To study the relationship in a nonepileptic population, the investigators sought out women aged 18–45 years in STEP-BD who were taking at least one mood stabilizer for at least 3 months.

Participants who had discontinued another mood stabilizer within the previous 3 months were not included in the substudy.

Of the 300 identified eligible women, 14 patients previously diagnosed with PCOS and three others with disorders involving oligomenorrhea were among those excluded from the sample. All told, 230 women were available for the analysis.

Of the valproate users, 12 developed oligomenorrhea, and 9 of them also had hirsutism, according to the report.

Among all patients with oligomenorrhea, valproate users had fewer menstrual cycles (median of 5 vs. 8.5 per year) than did nonusers.

Some had elevated total or free testosterone, moderate to severe acne, or male-pattern alopecia.

The valproate users who developed oligomenorrhea with hyperandrogenism had a higher median body mass index (kg/m

“Our study raises the possibility that increased body weight, insulin resistance, PCO morphology, younger age of first valproate use, and polypharmacy may predispose to the development of PCOS features on valproate,” the investigators concluded.

Women taking valproate for bipolar disorder are at significantly increased risk of developing features of polycystic ovary syndrome, according to a published study of 230 female patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial.

Investigators reported finding new-onset oligomenorrhea with hyperandrogenism in 9 (10.5%) of 86 women treated with valproate (Biol. Psychiatry 2006;59:1078–86).

Only 2 (1.4%) of 144 women on lithium or an anticonvulsant other than valproate developed these symptoms of polycystic ovary syndrome (PCOS).

In all cases, oligomenorrhea began within a year of the patient's starting valproate use. The investigators calculated the relative risk as 7.5 for women with bipolar disorder using valproate as a mood stabilizer.

Dr. Hadine Joffe, the lead author, is director of endocrine studies in the perinatal and reproductive psychiatry clinical research program at Massachusetts General Hospital in Boston.

She and her colleagues recommended warning women of PCOS risk before starting them on valproate.

Further, women on valproate should be evaluated for PCOS if they develop menstrual irregularities with hyperandrogenic symptoms. Along with PCOS treatment, the investigators suggested that “it may also be appropriate to consider alternative mood stabilizers if PCOS features develop on valproate.”

In an address at a psychiatric symposium sponsored by the University of Arizona, Dr. Gary Sachs, senior author and principal investigator of STEP-BD, emphasized the need for vigilance during the first year a patient is on valproate.

“Before you start women on valproate, you absolutely have to warn them this is a risk,” Dr. Sachs, founder and director of the bipolar clinic and research program at Massachusetts General Hospital, told psychiatrists at the Santa Fe, N.M., symposium, which was also sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Sponsored by the National Institute of Mental Health, STEP-BD enrolled 4,361 patients in the largest clinical study to date on the treatment of bipolar disorder. Dr. Sachs said that Abbott Laboratories, which sells valproate under the brand name Depakote, was among the drug companies that supported the trial.

“They were very confident the risk wasn't there,” he said. “It turned out that was wrong. There really was a risk. The risks are there and published.”

To study the relationship in a nonepileptic population, the investigators sought out women aged 18–45 years in STEP-BD who were taking at least one mood stabilizer for at least 3 months.

Participants who had discontinued another mood stabilizer within the previous 3 months were not included in the substudy.

Of the 300 identified eligible women, 14 patients previously diagnosed with PCOS and three others with disorders involving oligomenorrhea were among those excluded from the sample. All told, 230 women were available for the analysis.

Of the valproate users, 12 developed oligomenorrhea, and 9 of them also had hirsutism, according to the report.

Among all patients with oligomenorrhea, valproate users had fewer menstrual cycles (median of 5 vs. 8.5 per year) than did nonusers.

Some had elevated total or free testosterone, moderate to severe acne, or male-pattern alopecia.

The valproate users who developed oligomenorrhea with hyperandrogenism had a higher median body mass index (kg/m

“Our study raises the possibility that increased body weight, insulin resistance, PCO morphology, younger age of first valproate use, and polypharmacy may predispose to the development of PCOS features on valproate,” the investigators concluded.

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.