Diana Mahoney

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

SAN ANTONIO – Adding zoledronic acid to adjuvant endocrine therapy significantly improves disease-free and overall survival in premenopausal women with endocrine-receptor–positive early breast cancer at 7 years’ follow-up, Dr. Michael Gnant reported today at the San Antonio Breast Cancer Symposium.

Women in the ABCSG (Austrian Breast and Colorectal Cancer Study Group)-12 trial randomized to receive zoledronic acid in addition to ovarian function suppression and endocrine therapy had a 28% reduction in risk of recurrence and 37% reduction in mortality risk at 84 months, compared with women randomized to adjuvant endocrine therapy alone, according to Dr. Gnant, professor of surgery at the Medical University of Vienna.

The findings confirm data previously reported by the ABCSG-12 investigators demonstrating disease-free and overall survival benefits associated with the treatment regimen at 48 and 62 months of follow up (Lancet Oncol. 2011;12:631-41). "The continued success of this treatment means we can intervene early and still observe persistence of the benefit of treatment," said Dr. Gnant, president of the ABSCG.

The four-arm open-label trial randomly assigned 1,803 women to ovarian suppression and endocrine therapy plus or minus zoledronic acid for 3 years. Investigators used log-rank tests and Cox models to evaluate disease-free survival and overall survival, Dr. Gnant explained.

All of the patients, mean age 44.5 years, were premenopausal and had undergone surgery for stage I or II hormone receptor–positive breast cancer. They were treated for 3 years with 3.6 mg subcutaneous goserelin every 28 days, and randomized to 20 mg of oral tamoxifen daily plus placebo, 1 mg of oral anastrozole daily plus placebo, or either of the latter with 4 mg intravenous zoledronic acid every 6 months.

At a median 84 months’ follow-up, the hazard ratios for breast cancer recurrence and death, respectively, for women receiving adjuvant zoledronic acid were .72 and .63, Dr. Gnant reported, noting that the reductions remained significant in univariate and multivariate analyses. Further, in multivariate analysis, "there was no interaction between zoledronic acid and tumor parameters or endocrine therapy," he said. "The hazard ratios were identical for small and large tumors, node-positive and node-negative tumors, and for patients receiving anastrozole and tamoxifen."

There was a strong interaction between zoledronic acid and age in terms of survival benefit, however, with patients older than 40 years experiencing a 34% reduction in recurrence risk and a 44% reduction in mortality, according to Dr. Gnant. No similarly significant survival benefits were observed among patients younger than 40 years, he said.

As expected, patients receiving zoledronic acid experienced more arthralgia, Dr. Gnant stated, "but, importantly, there were no cases of osteonecrosis of the jaw and no renal failure in the treatment population."

The findings, which are consistent with those seen in the postmenopausal cohort of the AZURE trial, "suggest that estrogen deprivation and reduction of bone turnover-derived growth factors in the bone marrow microenvironment are needed to sufficiently suppress dormant micrometastases," Dr. Gnant explained. Together with the known bone-protective benefits of zoledronic acid, the new data provide sufficient support for adding the bisphosphonate to adjuvant endocrine therapy in premenopausal women with early endocrine-receptor–positive breast cancer, he said.

Dr. James N. Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session, concluded that the ABCSG-12 findings provide level-one evidence for the value of adding zoledronic acid to goserelin and tamoxifen or anastrozole in this patient population. "Zoledronic acid as standard of care [in these patients] will be more widely accepted when the results of the ongoing SOFT [Suppression of Ovarian Function trial] are reported," which will clarify the value of tamoxifen vs. exemestane (Aromasin) in conjunction with ovarian suppression, he said.

Dr. Gnant and Dr. Ingle reported having no relevant financial disclosures.

A new tracking system for monitoring antibiotic use in hospitals will enable the identification of antibiotic prescribing patterns within and between institutions with an eye toward reducing unnecessary or inappropriate use and, ultimately, minimizing the emergence of antimicrobial resistant pathogens and Clostridium difficile.

The electronic system is part of the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN), a secure, Internet-based surveillance system that monitors infections in more than 4,800 healthcare facilities nationwide, according to a statement released by the agency. The CDC has funded four health departments and their academic partners to implement the system in 70 hospitals, and all hospitals that participate in the NHSN can use the electronic monitoring tool by working with their pharmacy software vendors. The vendors can transmit prescription data electronically from drug administration or barcoding records, obviating the need for manual data entry, according to the statement.

The CDC announced the tool as part of the 2011 observance of "Get Smart About Antibiotics Week," an international collaboration designed to educate consumers and health care providers about inappropriate use of antibiotics. Concurrent with its Get Smart About Antibiotics Week program, the CDC also announced its partnership with the Institute for Healthcare Improvement to pilot test a tool designed to help hospitals implement strategies to improve antibiotic use as part of a joint initiative called the CDC IHI Driver Diagram and Change Package for Antibiotic Stewardship.

Antimicrobial stewardship – prescribing the right dose of the right antibiotic for the right duration – improves patient outcomes and saves health care dollars, according to Dr. Arjun Srinivasan, director of the CDC’s "Get Smart for Healthcare program."

"Although previously unthinkable, the day when antibiotics don’t work in all situations is upon us. We are already seeing germs that are stronger than any antibiotics we have to treat them, including some infections in health care settings," he stated in the CDC press release.

As leaders of multidisciplinary teams providing inpatient care, hospitalists, in particular, have an important role to play with respect to optimizing antimicrobial use, Dr. Srinivasan said in a recent report. Through the timely and appropriate initiation of antibiotics, as well as the management of administration and de-escalation according to established guidelines, hospitalists are well positioned to advance antimicrobial stewardship, he wrote (J. Hosp. Med. 2011 6[Suppl 1]:S31-3).

Dr. Srinivasan said he had no relevant conflicts of interest.

A new tracking system for monitoring antibiotic use in hospitals will enable the identification of antibiotic prescribing patterns within and between institutions with an eye toward reducing unnecessary or inappropriate use and, ultimately, minimizing the emergence of antimicrobial resistant pathogens and Clostridium difficile.

The electronic system is part of the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN), a secure, Internet-based surveillance system that monitors infections in more than 4,800 healthcare facilities nationwide, according to a statement released by the agency. The CDC has funded four health departments and their academic partners to implement the system in 70 hospitals, and all hospitals that participate in the NHSN can use the electronic monitoring tool by working with their pharmacy software vendors. The vendors can transmit prescription data electronically from drug administration or barcoding records, obviating the need for manual data entry, according to the statement.

The CDC announced the tool as part of the 2011 observance of "Get Smart About Antibiotics Week," an international collaboration designed to educate consumers and health care providers about inappropriate use of antibiotics. Concurrent with its Get Smart About Antibiotics Week program, the CDC also announced its partnership with the Institute for Healthcare Improvement to pilot test a tool designed to help hospitals implement strategies to improve antibiotic use as part of a joint initiative called the CDC IHI Driver Diagram and Change Package for Antibiotic Stewardship.

Antimicrobial stewardship – prescribing the right dose of the right antibiotic for the right duration – improves patient outcomes and saves health care dollars, according to Dr. Arjun Srinivasan, director of the CDC’s "Get Smart for Healthcare program."

"Although previously unthinkable, the day when antibiotics don’t work in all situations is upon us. We are already seeing germs that are stronger than any antibiotics we have to treat them, including some infections in health care settings," he stated in the CDC press release.

As leaders of multidisciplinary teams providing inpatient care, hospitalists, in particular, have an important role to play with respect to optimizing antimicrobial use, Dr. Srinivasan said in a recent report. Through the timely and appropriate initiation of antibiotics, as well as the management of administration and de-escalation according to established guidelines, hospitalists are well positioned to advance antimicrobial stewardship, he wrote (J. Hosp. Med. 2011 6[Suppl 1]:S31-3).

Dr. Srinivasan said he had no relevant conflicts of interest.

A new tracking system for monitoring antibiotic use in hospitals will enable the identification of antibiotic prescribing patterns within and between institutions with an eye toward reducing unnecessary or inappropriate use and, ultimately, minimizing the emergence of antimicrobial resistant pathogens and Clostridium difficile.

The electronic system is part of the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN), a secure, Internet-based surveillance system that monitors infections in more than 4,800 healthcare facilities nationwide, according to a statement released by the agency. The CDC has funded four health departments and their academic partners to implement the system in 70 hospitals, and all hospitals that participate in the NHSN can use the electronic monitoring tool by working with their pharmacy software vendors. The vendors can transmit prescription data electronically from drug administration or barcoding records, obviating the need for manual data entry, according to the statement.

The CDC announced the tool as part of the 2011 observance of "Get Smart About Antibiotics Week," an international collaboration designed to educate consumers and health care providers about inappropriate use of antibiotics. Concurrent with its Get Smart About Antibiotics Week program, the CDC also announced its partnership with the Institute for Healthcare Improvement to pilot test a tool designed to help hospitals implement strategies to improve antibiotic use as part of a joint initiative called the CDC IHI Driver Diagram and Change Package for Antibiotic Stewardship.

Antimicrobial stewardship – prescribing the right dose of the right antibiotic for the right duration – improves patient outcomes and saves health care dollars, according to Dr. Arjun Srinivasan, director of the CDC’s "Get Smart for Healthcare program."

"Although previously unthinkable, the day when antibiotics don’t work in all situations is upon us. We are already seeing germs that are stronger than any antibiotics we have to treat them, including some infections in health care settings," he stated in the CDC press release.

As leaders of multidisciplinary teams providing inpatient care, hospitalists, in particular, have an important role to play with respect to optimizing antimicrobial use, Dr. Srinivasan said in a recent report. Through the timely and appropriate initiation of antibiotics, as well as the management of administration and de-escalation according to established guidelines, hospitalists are well positioned to advance antimicrobial stewardship, he wrote (J. Hosp. Med. 2011 6[Suppl 1]:S31-3).

Dr. Srinivasan said he had no relevant conflicts of interest.

PHILADELPHIA – Poor glycemic control is associated with decreased survival in diabetes patients on maintenance hemodialysis, according to a study presented at Kidney Week 2011.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh of the Harbor-UCLA Medical Center in Torrance, Calif.

Although some guidelines, such as those from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative, recommend that diabetic dialysis patients follow the American Diabetes Association targets for glycemic control (hemoglobin A_1c less than 7%), "there is no consistent evidence to support these targets in dialysis patients," Dr. Kalantar-Zadeh said, noting that recent studies with different methodologies have reached opposing conclusions.

To determine the predictive value of glycemic control on mortality, Dr. Kalantar-Zadeh and his colleagues evaluated the association between HbA_1c and random serum glucose and survival in a large, contemporary cohort of diabetes patients treated at DaVita dialysis clinics from July 2001 to June 2006 with follow-up through June 2007.

Of 164,789 hemodialysis patients, the investigators identified 54,757 with diabetes for whom HbA_1c data were available, and analyzed death hazard ratios according to HbA_1c values and serum glucose levels, Dr. Kalantar-Zadeh explained. The adjusted all-cause death hazard ratio for baseline HbA_1c increments of 8.0%-8.9%, 9.0%-9.9%, and 10% or greater, respectively, were 1.06, 1.05, and 1.19, compared with a reference HbA_1c value of 7.0%-7.9%; the respective all-cause death hazard ratios for time-averaged HbA_1c were 1.11, 1.36, and 1.59, he said, noting that "a similarly consistent increase in cardiovascular mortality" was also observed.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh.

In fully adjusted models, decreased survival was also directly associated with time-averaged HbA_1c levels in the low range, with all-cause-death hazard ratios of 1.05, 1.08, and 1.35, respectively, for baseline HbA_1c values of 6.0-6.9%, 5.0-5.9%, and less than 5%, compared with 7.0-7.9%, Dr. Kalantar-Zadeh said. Further, the adjusted all-cause-death hazard ratios for time-averaged blood glucose levels of 175-199 mg/dL, 200-249 mg/dL, 250-299 mg/dL, and 300 mg/dL or higher were 1.03, 1.14, 1.30, and 1.66, respectively, compared with the reference range of 150-175 mg/dL.

The results are limited by the fact that HbA_1c levels are known to significantly underestimate glycemic control in hemodialysis patients, Dr. Kalantar-Zadeh acknowledged at the meeting, sponsored by the American Society of Nephrology. Also, "the information on comorbidity in our study was limited to that obtained from Medical Evidence Form 2728, in which comorbid conditions are significantly underestimated," he said. Lastly, "the study data did not include information on diabetes medication used at home or treatment adherence."

Limitations notwithstanding, the findings indicate that poor glycemic control (defined as HbA_1c of 8% or greater or a serum glucose level of 200mg/dL) is associated with death in diabetes patients on maintenance hemodialysis, and, unlike most diabetic patients, "those with kidney failure do not benefit from HbA_1c levels lower than 7%," Dr. Kalantar-Zadeh said. It appears that the most beneficial percentage is somewhere inside 6-8% in this patient population, "although controlled clinical trials to target HbA_1c at 6-8% are needed to determine the optimal range," he concluded.

Dr. Kalantar-Zadeh disclosed financial relationships with Abbott, Amgen, DaVita, Fresenius, Otsuka, Shire, Vifor, the National Institutes of Health, and the National Kidney Foundation. The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

PHILADELPHIA – Poor glycemic control is associated with decreased survival in diabetes patients on maintenance hemodialysis, according to a study presented at Kidney Week 2011.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh of the Harbor-UCLA Medical Center in Torrance, Calif.

Although some guidelines, such as those from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative, recommend that diabetic dialysis patients follow the American Diabetes Association targets for glycemic control (hemoglobin A_1c less than 7%), "there is no consistent evidence to support these targets in dialysis patients," Dr. Kalantar-Zadeh said, noting that recent studies with different methodologies have reached opposing conclusions.

To determine the predictive value of glycemic control on mortality, Dr. Kalantar-Zadeh and his colleagues evaluated the association between HbA_1c and random serum glucose and survival in a large, contemporary cohort of diabetes patients treated at DaVita dialysis clinics from July 2001 to June 2006 with follow-up through June 2007.

Of 164,789 hemodialysis patients, the investigators identified 54,757 with diabetes for whom HbA_1c data were available, and analyzed death hazard ratios according to HbA_1c values and serum glucose levels, Dr. Kalantar-Zadeh explained. The adjusted all-cause death hazard ratio for baseline HbA_1c increments of 8.0%-8.9%, 9.0%-9.9%, and 10% or greater, respectively, were 1.06, 1.05, and 1.19, compared with a reference HbA_1c value of 7.0%-7.9%; the respective all-cause death hazard ratios for time-averaged HbA_1c were 1.11, 1.36, and 1.59, he said, noting that "a similarly consistent increase in cardiovascular mortality" was also observed.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh.

In fully adjusted models, decreased survival was also directly associated with time-averaged HbA_1c levels in the low range, with all-cause-death hazard ratios of 1.05, 1.08, and 1.35, respectively, for baseline HbA_1c values of 6.0-6.9%, 5.0-5.9%, and less than 5%, compared with 7.0-7.9%, Dr. Kalantar-Zadeh said. Further, the adjusted all-cause-death hazard ratios for time-averaged blood glucose levels of 175-199 mg/dL, 200-249 mg/dL, 250-299 mg/dL, and 300 mg/dL or higher were 1.03, 1.14, 1.30, and 1.66, respectively, compared with the reference range of 150-175 mg/dL.

The results are limited by the fact that HbA_1c levels are known to significantly underestimate glycemic control in hemodialysis patients, Dr. Kalantar-Zadeh acknowledged at the meeting, sponsored by the American Society of Nephrology. Also, "the information on comorbidity in our study was limited to that obtained from Medical Evidence Form 2728, in which comorbid conditions are significantly underestimated," he said. Lastly, "the study data did not include information on diabetes medication used at home or treatment adherence."

Limitations notwithstanding, the findings indicate that poor glycemic control (defined as HbA_1c of 8% or greater or a serum glucose level of 200mg/dL) is associated with death in diabetes patients on maintenance hemodialysis, and, unlike most diabetic patients, "those with kidney failure do not benefit from HbA_1c levels lower than 7%," Dr. Kalantar-Zadeh said. It appears that the most beneficial percentage is somewhere inside 6-8% in this patient population, "although controlled clinical trials to target HbA_1c at 6-8% are needed to determine the optimal range," he concluded.

Dr. Kalantar-Zadeh disclosed financial relationships with Abbott, Amgen, DaVita, Fresenius, Otsuka, Shire, Vifor, the National Institutes of Health, and the National Kidney Foundation. The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

PHILADELPHIA – Poor glycemic control is associated with decreased survival in diabetes patients on maintenance hemodialysis, according to a study presented at Kidney Week 2011.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh of the Harbor-UCLA Medical Center in Torrance, Calif.

Although some guidelines, such as those from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative, recommend that diabetic dialysis patients follow the American Diabetes Association targets for glycemic control (hemoglobin A_1c less than 7%), "there is no consistent evidence to support these targets in dialysis patients," Dr. Kalantar-Zadeh said, noting that recent studies with different methodologies have reached opposing conclusions.

To determine the predictive value of glycemic control on mortality, Dr. Kalantar-Zadeh and his colleagues evaluated the association between HbA_1c and random serum glucose and survival in a large, contemporary cohort of diabetes patients treated at DaVita dialysis clinics from July 2001 to June 2006 with follow-up through June 2007.

Of 164,789 hemodialysis patients, the investigators identified 54,757 with diabetes for whom HbA_1c data were available, and analyzed death hazard ratios according to HbA_1c values and serum glucose levels, Dr. Kalantar-Zadeh explained. The adjusted all-cause death hazard ratio for baseline HbA_1c increments of 8.0%-8.9%, 9.0%-9.9%, and 10% or greater, respectively, were 1.06, 1.05, and 1.19, compared with a reference HbA_1c value of 7.0%-7.9%; the respective all-cause death hazard ratios for time-averaged HbA_1c were 1.11, 1.36, and 1.59, he said, noting that "a similarly consistent increase in cardiovascular mortality" was also observed.

Not only does too much glucose increase the risk of all-cause and cardiovascular mortality in this patient population, too little does as well, according to Dr. Kamyar Kalantar-Zadeh.

In fully adjusted models, decreased survival was also directly associated with time-averaged HbA_1c levels in the low range, with all-cause-death hazard ratios of 1.05, 1.08, and 1.35, respectively, for baseline HbA_1c values of 6.0-6.9%, 5.0-5.9%, and less than 5%, compared with 7.0-7.9%, Dr. Kalantar-Zadeh said. Further, the adjusted all-cause-death hazard ratios for time-averaged blood glucose levels of 175-199 mg/dL, 200-249 mg/dL, 250-299 mg/dL, and 300 mg/dL or higher were 1.03, 1.14, 1.30, and 1.66, respectively, compared with the reference range of 150-175 mg/dL.

The results are limited by the fact that HbA_1c levels are known to significantly underestimate glycemic control in hemodialysis patients, Dr. Kalantar-Zadeh acknowledged at the meeting, sponsored by the American Society of Nephrology. Also, "the information on comorbidity in our study was limited to that obtained from Medical Evidence Form 2728, in which comorbid conditions are significantly underestimated," he said. Lastly, "the study data did not include information on diabetes medication used at home or treatment adherence."

Limitations notwithstanding, the findings indicate that poor glycemic control (defined as HbA_1c of 8% or greater or a serum glucose level of 200mg/dL) is associated with death in diabetes patients on maintenance hemodialysis, and, unlike most diabetic patients, "those with kidney failure do not benefit from HbA_1c levels lower than 7%," Dr. Kalantar-Zadeh said. It appears that the most beneficial percentage is somewhere inside 6-8% in this patient population, "although controlled clinical trials to target HbA_1c at 6-8% are needed to determine the optimal range," he concluded.

Dr. Kalantar-Zadeh disclosed financial relationships with Abbott, Amgen, DaVita, Fresenius, Otsuka, Shire, Vifor, the National Institutes of Health, and the National Kidney Foundation. The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

PHILADELPHIA – The detection of urinary podocytes in mid-pregnancy is a highly sensitive and specific marker for preeclampsia and may be the first reliable tool for predicting which women will develop the potentially life-threatening hypertensive complication, according to Dr. Iasmina M. Craici.

Previously, investigators determined that the urinary excretion of viable podocytes (glomerular epithelial cells) was significantly higher in patients with preeclampsia, compared with normotensive patients, and that it had a greater positive predictive value for diagnosing preeclampsia than certain specific angiogenic factors of the condition (Am. J. Obstet. Gynecol. 2007;196:320.e1-7).

"There are currently no tests that will reliably predict who will develop preeclampsia, so the possibility of being able to identify, in mid-gestation, those women who will later go on to develop preeclampsia is especially important," Dr. Craici stated. "It will give us the opportunity to implement early treatment of severe high blood pressure and by doing so will improve maternal and fetal outcomes," she said.

The current study was designed to ascertain whether podocyturia is present in the urine before the onset of preeclampsia and whether it can be used to differentiate between preeclampsia, gestational hypertension, and normal pregnancy, said Dr. Craici of the Mayo Clinic in Rochester, Minn.

From a prospective cohort of 315 patients, 267 successful deliveries were included in the final analysis. Of these, 204 women had normal pregnancies and 30 had hypertensive pregnancies, including 15 cases each of preeclampsia and gestational hypertension, Dr. Craici reported at Kidney Week 2011, sponsored by the American Society of Nephrology. The remaining 33 pregnancies were complicated by other problems, including gestational diabetes, intrauterine growth retardation, and preterm delivery, she said.

All patients had their blood pressure and protein/creatinine ratios checked at mid-gestation (weeks 25-28), prior to the onset of preeclampsia or gestational hypertension. Urine sediments collected in mid-pregnancy, prior to 210 days gestation, were cultured for 24 hours to select for viable cells, "and we identified podocytes using podocin staining," Dr. Craici explained. For purposes of the comparative analysis, 45 patients were selected from the normal pregnancy group as controls, she said, noting that there was no age difference between the groups.

At mid-pregnancy, "none of the 45 normotensive or the 15 gestational hypertensive women had podocyturia present in their urine specimens, but it was present in the urine of all of the preeclamptic women," said Dr. Craici. At this time point, she said, none of the women who would later develop preeclampsia had signs of the condition. "They did not have hypertension, nor did they yet have protein in the urine."

At delivery, podocyturia was again absent in all of the normotensive pregnancies and present in all of the preeclamptic pregnancies, Dr. Craici said, noting that it was present in only one of the women with gestational hypertension.

Dr. Craici disclosed that the technology used in this research has been licensed to a commercial entity and that senior investigator Dr. Vesna D. Garovic and the Mayo Clinic have contractual rights to receive royalties from the licensing of the technology.

PHILADELPHIA – The detection of urinary podocytes in mid-pregnancy is a highly sensitive and specific marker for preeclampsia and may be the first reliable tool for predicting which women will develop the potentially life-threatening hypertensive complication, according to Dr. Iasmina M. Craici.

Previously, investigators determined that the urinary excretion of viable podocytes (glomerular epithelial cells) was significantly higher in patients with preeclampsia, compared with normotensive patients, and that it had a greater positive predictive value for diagnosing preeclampsia than certain specific angiogenic factors of the condition (Am. J. Obstet. Gynecol. 2007;196:320.e1-7).

"There are currently no tests that will reliably predict who will develop preeclampsia, so the possibility of being able to identify, in mid-gestation, those women who will later go on to develop preeclampsia is especially important," Dr. Craici stated. "It will give us the opportunity to implement early treatment of severe high blood pressure and by doing so will improve maternal and fetal outcomes," she said.

The current study was designed to ascertain whether podocyturia is present in the urine before the onset of preeclampsia and whether it can be used to differentiate between preeclampsia, gestational hypertension, and normal pregnancy, said Dr. Craici of the Mayo Clinic in Rochester, Minn.

From a prospective cohort of 315 patients, 267 successful deliveries were included in the final analysis. Of these, 204 women had normal pregnancies and 30 had hypertensive pregnancies, including 15 cases each of preeclampsia and gestational hypertension, Dr. Craici reported at Kidney Week 2011, sponsored by the American Society of Nephrology. The remaining 33 pregnancies were complicated by other problems, including gestational diabetes, intrauterine growth retardation, and preterm delivery, she said.

All patients had their blood pressure and protein/creatinine ratios checked at mid-gestation (weeks 25-28), prior to the onset of preeclampsia or gestational hypertension. Urine sediments collected in mid-pregnancy, prior to 210 days gestation, were cultured for 24 hours to select for viable cells, "and we identified podocytes using podocin staining," Dr. Craici explained. For purposes of the comparative analysis, 45 patients were selected from the normal pregnancy group as controls, she said, noting that there was no age difference between the groups.

At mid-pregnancy, "none of the 45 normotensive or the 15 gestational hypertensive women had podocyturia present in their urine specimens, but it was present in the urine of all of the preeclamptic women," said Dr. Craici. At this time point, she said, none of the women who would later develop preeclampsia had signs of the condition. "They did not have hypertension, nor did they yet have protein in the urine."

At delivery, podocyturia was again absent in all of the normotensive pregnancies and present in all of the preeclamptic pregnancies, Dr. Craici said, noting that it was present in only one of the women with gestational hypertension.

Dr. Craici disclosed that the technology used in this research has been licensed to a commercial entity and that senior investigator Dr. Vesna D. Garovic and the Mayo Clinic have contractual rights to receive royalties from the licensing of the technology.

PHILADELPHIA – The detection of urinary podocytes in mid-pregnancy is a highly sensitive and specific marker for preeclampsia and may be the first reliable tool for predicting which women will develop the potentially life-threatening hypertensive complication, according to Dr. Iasmina M. Craici.

Previously, investigators determined that the urinary excretion of viable podocytes (glomerular epithelial cells) was significantly higher in patients with preeclampsia, compared with normotensive patients, and that it had a greater positive predictive value for diagnosing preeclampsia than certain specific angiogenic factors of the condition (Am. J. Obstet. Gynecol. 2007;196:320.e1-7).

"There are currently no tests that will reliably predict who will develop preeclampsia, so the possibility of being able to identify, in mid-gestation, those women who will later go on to develop preeclampsia is especially important," Dr. Craici stated. "It will give us the opportunity to implement early treatment of severe high blood pressure and by doing so will improve maternal and fetal outcomes," she said.

The current study was designed to ascertain whether podocyturia is present in the urine before the onset of preeclampsia and whether it can be used to differentiate between preeclampsia, gestational hypertension, and normal pregnancy, said Dr. Craici of the Mayo Clinic in Rochester, Minn.

From a prospective cohort of 315 patients, 267 successful deliveries were included in the final analysis. Of these, 204 women had normal pregnancies and 30 had hypertensive pregnancies, including 15 cases each of preeclampsia and gestational hypertension, Dr. Craici reported at Kidney Week 2011, sponsored by the American Society of Nephrology. The remaining 33 pregnancies were complicated by other problems, including gestational diabetes, intrauterine growth retardation, and preterm delivery, she said.

All patients had their blood pressure and protein/creatinine ratios checked at mid-gestation (weeks 25-28), prior to the onset of preeclampsia or gestational hypertension. Urine sediments collected in mid-pregnancy, prior to 210 days gestation, were cultured for 24 hours to select for viable cells, "and we identified podocytes using podocin staining," Dr. Craici explained. For purposes of the comparative analysis, 45 patients were selected from the normal pregnancy group as controls, she said, noting that there was no age difference between the groups.

At mid-pregnancy, "none of the 45 normotensive or the 15 gestational hypertensive women had podocyturia present in their urine specimens, but it was present in the urine of all of the preeclamptic women," said Dr. Craici. At this time point, she said, none of the women who would later develop preeclampsia had signs of the condition. "They did not have hypertension, nor did they yet have protein in the urine."

At delivery, podocyturia was again absent in all of the normotensive pregnancies and present in all of the preeclamptic pregnancies, Dr. Craici said, noting that it was present in only one of the women with gestational hypertension.

Dr. Craici disclosed that the technology used in this research has been licensed to a commercial entity and that senior investigator Dr. Vesna D. Garovic and the Mayo Clinic have contractual rights to receive royalties from the licensing of the technology.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said in a late-breaking presentation at Kidney Week 2011.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/minute per 1.73 m² of body surface area at two consecutive study visits – among individuals randomly assigned to intensive diabetes treatment versus those assigned to conventional treatment over a 22-year median follow-up.

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients) consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms or to intensive diabetes treatment (711 patients) consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, "as close to the nondiabetic range as possible," Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. "In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference," said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, "70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment," Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period. The time of the events is important, he said. "Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization."

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, "the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy," representing an absolute risk reduction of 3.5%, he explained. Through the follow-up period, 8 patients in the intensive treatment group and 16 in the conventional treatment group developed end-stage kidney disease.

The reduction in the mean estimated GFR was greater in the intensive vs. conventional treatment groups during the DCCT, at a rate of 1.7 mL/min per 1.73 m², but during the EDIC study, "intensive therapy was associated with a slower rate of GFR reduction and an increase in the mean estimated GFR of 2.5 mL/min per 1.73 m²," Dr. de Boer said. After adjustment for glycated hemoglobin levels or albumin excretion rates, "the beneficial effect [of intensive therapy on the risk of GFR impairment] was fully attenuated," he noted.

The findings demonstrate the enduring kidney benefits of intensive diabetes treatment early in the disease course, according to Dr. de Boer. "After combining these data with previous reports that DCCT intensive therapy reduces the risk of retinopathy, neuropathy, albuminuria, and cardiovascular disease, these results support current recommendations to target hemoglobin A_1c in the care of patients with type 1 diabetes," he stated. The results cannot be extrapolated to the treatment of individuals with type 2 diabetes, he said.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011 Nov. 12 [doi:10.1056/NEJMoa1111732]).

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said in a late-breaking presentation at Kidney Week 2011.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/minute per 1.73 m² of body surface area at two consecutive study visits – among individuals randomly assigned to intensive diabetes treatment versus those assigned to conventional treatment over a 22-year median follow-up.

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients) consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms or to intensive diabetes treatment (711 patients) consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, "as close to the nondiabetic range as possible," Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. "In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference," said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, "70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment," Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period. The time of the events is important, he said. "Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization."

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, "the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy," representing an absolute risk reduction of 3.5%, he explained. Through the follow-up period, 8 patients in the intensive treatment group and 16 in the conventional treatment group developed end-stage kidney disease.

The reduction in the mean estimated GFR was greater in the intensive vs. conventional treatment groups during the DCCT, at a rate of 1.7 mL/min per 1.73 m², but during the EDIC study, "intensive therapy was associated with a slower rate of GFR reduction and an increase in the mean estimated GFR of 2.5 mL/min per 1.73 m²," Dr. de Boer said. After adjustment for glycated hemoglobin levels or albumin excretion rates, "the beneficial effect [of intensive therapy on the risk of GFR impairment] was fully attenuated," he noted.

The findings demonstrate the enduring kidney benefits of intensive diabetes treatment early in the disease course, according to Dr. de Boer. "After combining these data with previous reports that DCCT intensive therapy reduces the risk of retinopathy, neuropathy, albuminuria, and cardiovascular disease, these results support current recommendations to target hemoglobin A_1c in the care of patients with type 1 diabetes," he stated. The results cannot be extrapolated to the treatment of individuals with type 2 diabetes, he said.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011 Nov. 12 [doi:10.1056/NEJMoa1111732]).

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said in a late-breaking presentation at Kidney Week 2011.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/minute per 1.73 m² of body surface area at two consecutive study visits – among individuals randomly assigned to intensive diabetes treatment versus those assigned to conventional treatment over a 22-year median follow-up.

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients) consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms or to intensive diabetes treatment (711 patients) consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, "as close to the nondiabetic range as possible," Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. "In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference," said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, "70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment," Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period. The time of the events is important, he said. "Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization."

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, "the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy," representing an absolute risk reduction of 3.5%, he explained. Through the follow-up period, 8 patients in the intensive treatment group and 16 in the conventional treatment group developed end-stage kidney disease.

The reduction in the mean estimated GFR was greater in the intensive vs. conventional treatment groups during the DCCT, at a rate of 1.7 mL/min per 1.73 m², but during the EDIC study, "intensive therapy was associated with a slower rate of GFR reduction and an increase in the mean estimated GFR of 2.5 mL/min per 1.73 m²," Dr. de Boer said. After adjustment for glycated hemoglobin levels or albumin excretion rates, "the beneficial effect [of intensive therapy on the risk of GFR impairment] was fully attenuated," he noted.

The findings demonstrate the enduring kidney benefits of intensive diabetes treatment early in the disease course, according to Dr. de Boer. "After combining these data with previous reports that DCCT intensive therapy reduces the risk of retinopathy, neuropathy, albuminuria, and cardiovascular disease, these results support current recommendations to target hemoglobin A_1c in the care of patients with type 1 diabetes," he stated. The results cannot be extrapolated to the treatment of individuals with type 2 diabetes, he said.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011 Nov. 12 [doi:10.1056/NEJMoa1111732]).

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

PHILADELPHIA – Race, socioeconomic status, and insurance status all impact survival for children with end-stage renal disease, with poor, uninsured black children at greater risk of death than all others.

Dr. Sandra G. Amaral of Children’s Hospital of Philadelphia and her colleagues used information from the United States Renal Data System to identify racial and socioeconomic disparities associated with mortality risk in pediatric end-stage renal disease (ESRD).

"We know that, among children with [ESRD], death risk is much lower for those who receive a kidney transplant, compared with those who stay on dialysis, but we don’t know much about which children die before reaching transplant," Dr. Amaral said. "We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

They identified 8,146 patients younger than 21 years who had been diagnosed with ESRD from Jan. 2000 through Sept. 2008 and followed through September 2009, looking at patients who were on dialysis but had not been transplanted and whose race/ethnicity was white, Hispanic, or black. Of the 8,146 children, 896 died before reaching transplant, she said at the meeting, sponsored by the American Society of Nephrology.

"We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

Of the patients who died, 357 were white, 161 were Hispanic, and 378 were black, Dr. Amaral said. By health insurance status, 179 were privately insured, 527 were publicly insured, 87 children were uninsured, and 103 were classified as "other," she said.

The number of children who died, independent of race/ethnicity, was related to neighborhood poverty. Specifically, 304 of the children who died had lived in the poorest neighborhoods – those where at least 20% of residents were at or below the federal poverty line – compared with 80 children from the wealthiest neighborhoods in which 0 to 4.9% of the residents had incomes at or below poverty level, she said.

"We saw significant differences by race, health insurance, and poverty among patients who were alive vs. those who died, and proportionally, among all of the black patients, more died than in any other subgroup," Dr. Amaral said, adding that "more patients among those who died had public insurance and were from poorer neighborhoods."

Survival curves showed that Hispanic children had the highest rate of survival, followed by white children. "Black children had the lowest rate of survival," Dr. Amaral stated. In an analysis adjusted for age, gender, and diagnosis, "the poorest children, regardless of race, had higher mortality."

However, the risk of death among those of different ethnic backgrounds varied by type of health insurance and not by poverty. "Uninsured black children, for example, had a 78% increased risk, compared with uninsured white children," she said, while black children with private insurance had only a 19% increased risk, compared with privately insured white children.

The current findings are limited by the fact that the data set included only patients who had been diagnosed with ESRD, Dr. Amaral said.

"We don’t know what happened to them before that," she said. "There may be issues in patient access to care. It’s possible that the reason patients are not even getting wait-listed at diagnosis is that they’re too sick," she said.

Dr. Amaral disclosed having no financial conflicts of interest related to her presentation.

PHILADELPHIA – Race, socioeconomic status, and insurance status all impact survival for children with end-stage renal disease, with poor, uninsured black children at greater risk of death than all others.

Dr. Sandra G. Amaral of Children’s Hospital of Philadelphia and her colleagues used information from the United States Renal Data System to identify racial and socioeconomic disparities associated with mortality risk in pediatric end-stage renal disease (ESRD).

"We know that, among children with [ESRD], death risk is much lower for those who receive a kidney transplant, compared with those who stay on dialysis, but we don’t know much about which children die before reaching transplant," Dr. Amaral said. "We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

They identified 8,146 patients younger than 21 years who had been diagnosed with ESRD from Jan. 2000 through Sept. 2008 and followed through September 2009, looking at patients who were on dialysis but had not been transplanted and whose race/ethnicity was white, Hispanic, or black. Of the 8,146 children, 896 died before reaching transplant, she said at the meeting, sponsored by the American Society of Nephrology.

"We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

Of the patients who died, 357 were white, 161 were Hispanic, and 378 were black, Dr. Amaral said. By health insurance status, 179 were privately insured, 527 were publicly insured, 87 children were uninsured, and 103 were classified as "other," she said.

The number of children who died, independent of race/ethnicity, was related to neighborhood poverty. Specifically, 304 of the children who died had lived in the poorest neighborhoods – those where at least 20% of residents were at or below the federal poverty line – compared with 80 children from the wealthiest neighborhoods in which 0 to 4.9% of the residents had incomes at or below poverty level, she said.

"We saw significant differences by race, health insurance, and poverty among patients who were alive vs. those who died, and proportionally, among all of the black patients, more died than in any other subgroup," Dr. Amaral said, adding that "more patients among those who died had public insurance and were from poorer neighborhoods."

Survival curves showed that Hispanic children had the highest rate of survival, followed by white children. "Black children had the lowest rate of survival," Dr. Amaral stated. In an analysis adjusted for age, gender, and diagnosis, "the poorest children, regardless of race, had higher mortality."

However, the risk of death among those of different ethnic backgrounds varied by type of health insurance and not by poverty. "Uninsured black children, for example, had a 78% increased risk, compared with uninsured white children," she said, while black children with private insurance had only a 19% increased risk, compared with privately insured white children.

The current findings are limited by the fact that the data set included only patients who had been diagnosed with ESRD, Dr. Amaral said.

"We don’t know what happened to them before that," she said. "There may be issues in patient access to care. It’s possible that the reason patients are not even getting wait-listed at diagnosis is that they’re too sick," she said.

Dr. Amaral disclosed having no financial conflicts of interest related to her presentation.

PHILADELPHIA – Race, socioeconomic status, and insurance status all impact survival for children with end-stage renal disease, with poor, uninsured black children at greater risk of death than all others.

Dr. Sandra G. Amaral of Children’s Hospital of Philadelphia and her colleagues used information from the United States Renal Data System to identify racial and socioeconomic disparities associated with mortality risk in pediatric end-stage renal disease (ESRD).

"We know that, among children with [ESRD], death risk is much lower for those who receive a kidney transplant, compared with those who stay on dialysis, but we don’t know much about which children die before reaching transplant," Dr. Amaral said. "We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

They identified 8,146 patients younger than 21 years who had been diagnosed with ESRD from Jan. 2000 through Sept. 2008 and followed through September 2009, looking at patients who were on dialysis but had not been transplanted and whose race/ethnicity was white, Hispanic, or black. Of the 8,146 children, 896 died before reaching transplant, she said at the meeting, sponsored by the American Society of Nephrology.

"We wanted to determine whether there are racial or ethnic differences in the risk of dying when children remain on dialysis."

Of the patients who died, 357 were white, 161 were Hispanic, and 378 were black, Dr. Amaral said. By health insurance status, 179 were privately insured, 527 were publicly insured, 87 children were uninsured, and 103 were classified as "other," she said.

The number of children who died, independent of race/ethnicity, was related to neighborhood poverty. Specifically, 304 of the children who died had lived in the poorest neighborhoods – those where at least 20% of residents were at or below the federal poverty line – compared with 80 children from the wealthiest neighborhoods in which 0 to 4.9% of the residents had incomes at or below poverty level, she said.

"We saw significant differences by race, health insurance, and poverty among patients who were alive vs. those who died, and proportionally, among all of the black patients, more died than in any other subgroup," Dr. Amaral said, adding that "more patients among those who died had public insurance and were from poorer neighborhoods."

Survival curves showed that Hispanic children had the highest rate of survival, followed by white children. "Black children had the lowest rate of survival," Dr. Amaral stated. In an analysis adjusted for age, gender, and diagnosis, "the poorest children, regardless of race, had higher mortality."

However, the risk of death among those of different ethnic backgrounds varied by type of health insurance and not by poverty. "Uninsured black children, for example, had a 78% increased risk, compared with uninsured white children," she said, while black children with private insurance had only a 19% increased risk, compared with privately insured white children.

The current findings are limited by the fact that the data set included only patients who had been diagnosed with ESRD, Dr. Amaral said.

"We don’t know what happened to them before that," she said. "There may be issues in patient access to care. It’s possible that the reason patients are not even getting wait-listed at diagnosis is that they’re too sick," she said.

Dr. Amaral disclosed having no financial conflicts of interest related to her presentation.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

PHILADELPHIA – The use of potentially nephrotoxic dietary supplements is common in the general U.S. population and among individuals with chronic kidney disease, a study has shown.

The findings suggest that chronic kidney disease patients and their physicians may be unaware of the dangers associated with supplementation, and also that physicians may be unaware that their patients are taking dietary supplements, Dr. Vanessa Grubbs reported Nov. 10 at the annual meeting of the American Society of Nephrology.

©Zlatko Ivancok/Fotolia.com

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys, regardless of kidney disease status," said Dr. Grubbs of the University of California, San Francisco. The irony, she noted, "is that these individuals believe they are improving their health by taking supplements, when they may be causing harm."

The National Kidney Foundation (NKF) has identified 39 herbs that may be harmful, particularly in the setting of chronic kidney disease, but physician oversight of patient intake is difficult, Dr. Grubbs said, "because the dietary supplements containing these herbs are regulated like foods, not like drugs."

Among the more common kidney-unfriendly herbs identified by the NKF are those that serve as diuretics, including bucha leaves and juniper berries, and those that interact with prescription drugs, such as St. John’s wort, echinacea, ginkgo, garlic, ginger, and blue cohosh.

To determine the prevalence of the use of supplements containing these herbs in the general U.S. population and by chronic kidney disease status, Dr. Grubbs and her colleagues used data from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) to ascertain the reported use of dietary supplements in the past 30 days among 21,169 nonpregnant adults over age 20. For purposes of the analysis, chronic kidney disease was defined by a urinary albumin-to-creatinine ratio of at least 30 mg/g with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m² or greater (stage I/II), or an eGFR of 15-59 mL/min/1.73 m² (stage III/IV), she said. To estimate the prevalence and odds of taking a potentially harmful supplement by chronic kidney disease status, "we used multivariate logistic regression weighted to the U.S. population," she said at the meeting sponsored by the American Society of Nephrology.

More than half (52.4%) of survey participants reported taking any dietary supplement, among which 15.3% reported taking a supplement containing at least one of the potentially harmful herbs, Dr. Grubbs reported. Although the crude estimated prevalence of individuals taking any dietary supplement increased with greater chronic kidney disease severity – with reported use by 51.4% of individuals with no kidney disease, 49.1% of those with stage I/II disease, and 65.8% of those with stage III/IV disease – it decreased among those taking a potentially harmful supplement – with reported use by 16.1%, 13.0%, and 10.0%, respectively, she said.

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys."

After adjusting for demographics, comorbid disease, and health care visits, however, "chronic kidney disease status was not a significant determinant of taking any supplement or of taking a potentially harmful supplement," Dr. Grubbs said.

The fact that so many individuals are taking supplements with ingredients that can be harmful to the kidneys is especially problematic, she stressed, "because many people with advanced kidney disease – up to 10% – are not aware that they have kidney disease." Further, she noted, the list of potentially harmful supplements may not be exhaustive, and because the supplements are not regulated as drugs, the amounts of the ingredients in question are unknown and thus may be more harmful than anticipated.

Until policy makers can be convinced to update the regulatory standards for dietary supplements, the onus for protecting patients is on physicians and on the patients themselves. "We have to educate ourselves about dietary supplements and ask patients about everything they are taking, and we have to educate our patients [about kidney disease] and the possibility of [supplements] doing more harm than good," Dr. Grubbs said.

Dr. Grubbs reported having no financial conflicts of interest.

PHILADELPHIA – The use of potentially nephrotoxic dietary supplements is common in the general U.S. population and among individuals with chronic kidney disease, a study has shown.

The findings suggest that chronic kidney disease patients and their physicians may be unaware of the dangers associated with supplementation, and also that physicians may be unaware that their patients are taking dietary supplements, Dr. Vanessa Grubbs reported Nov. 10 at the annual meeting of the American Society of Nephrology.

©Zlatko Ivancok/Fotolia.com

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys, regardless of kidney disease status," said Dr. Grubbs of the University of California, San Francisco. The irony, she noted, "is that these individuals believe they are improving their health by taking supplements, when they may be causing harm."

The National Kidney Foundation (NKF) has identified 39 herbs that may be harmful, particularly in the setting of chronic kidney disease, but physician oversight of patient intake is difficult, Dr. Grubbs said, "because the dietary supplements containing these herbs are regulated like foods, not like drugs."

Among the more common kidney-unfriendly herbs identified by the NKF are those that serve as diuretics, including bucha leaves and juniper berries, and those that interact with prescription drugs, such as St. John’s wort, echinacea, ginkgo, garlic, ginger, and blue cohosh.

To determine the prevalence of the use of supplements containing these herbs in the general U.S. population and by chronic kidney disease status, Dr. Grubbs and her colleagues used data from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) to ascertain the reported use of dietary supplements in the past 30 days among 21,169 nonpregnant adults over age 20. For purposes of the analysis, chronic kidney disease was defined by a urinary albumin-to-creatinine ratio of at least 30 mg/g with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m² or greater (stage I/II), or an eGFR of 15-59 mL/min/1.73 m² (stage III/IV), she said. To estimate the prevalence and odds of taking a potentially harmful supplement by chronic kidney disease status, "we used multivariate logistic regression weighted to the U.S. population," she said at the meeting sponsored by the American Society of Nephrology.

More than half (52.4%) of survey participants reported taking any dietary supplement, among which 15.3% reported taking a supplement containing at least one of the potentially harmful herbs, Dr. Grubbs reported. Although the crude estimated prevalence of individuals taking any dietary supplement increased with greater chronic kidney disease severity – with reported use by 51.4% of individuals with no kidney disease, 49.1% of those with stage I/II disease, and 65.8% of those with stage III/IV disease – it decreased among those taking a potentially harmful supplement – with reported use by 16.1%, 13.0%, and 10.0%, respectively, she said.

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys."

After adjusting for demographics, comorbid disease, and health care visits, however, "chronic kidney disease status was not a significant determinant of taking any supplement or of taking a potentially harmful supplement," Dr. Grubbs said.

The fact that so many individuals are taking supplements with ingredients that can be harmful to the kidneys is especially problematic, she stressed, "because many people with advanced kidney disease – up to 10% – are not aware that they have kidney disease." Further, she noted, the list of potentially harmful supplements may not be exhaustive, and because the supplements are not regulated as drugs, the amounts of the ingredients in question are unknown and thus may be more harmful than anticipated.

Until policy makers can be convinced to update the regulatory standards for dietary supplements, the onus for protecting patients is on physicians and on the patients themselves. "We have to educate ourselves about dietary supplements and ask patients about everything they are taking, and we have to educate our patients [about kidney disease] and the possibility of [supplements] doing more harm than good," Dr. Grubbs said.

Dr. Grubbs reported having no financial conflicts of interest.

PHILADELPHIA – The use of potentially nephrotoxic dietary supplements is common in the general U.S. population and among individuals with chronic kidney disease, a study has shown.

The findings suggest that chronic kidney disease patients and their physicians may be unaware of the dangers associated with supplementation, and also that physicians may be unaware that their patients are taking dietary supplements, Dr. Vanessa Grubbs reported Nov. 10 at the annual meeting of the American Society of Nephrology.

©Zlatko Ivancok/Fotolia.com

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys, regardless of kidney disease status," said Dr. Grubbs of the University of California, San Francisco. The irony, she noted, "is that these individuals believe they are improving their health by taking supplements, when they may be causing harm."

The National Kidney Foundation (NKF) has identified 39 herbs that may be harmful, particularly in the setting of chronic kidney disease, but physician oversight of patient intake is difficult, Dr. Grubbs said, "because the dietary supplements containing these herbs are regulated like foods, not like drugs."

Among the more common kidney-unfriendly herbs identified by the NKF are those that serve as diuretics, including bucha leaves and juniper berries, and those that interact with prescription drugs, such as St. John’s wort, echinacea, ginkgo, garlic, ginger, and blue cohosh.

To determine the prevalence of the use of supplements containing these herbs in the general U.S. population and by chronic kidney disease status, Dr. Grubbs and her colleagues used data from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) to ascertain the reported use of dietary supplements in the past 30 days among 21,169 nonpregnant adults over age 20. For purposes of the analysis, chronic kidney disease was defined by a urinary albumin-to-creatinine ratio of at least 30 mg/g with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m² or greater (stage I/II), or an eGFR of 15-59 mL/min/1.73 m² (stage III/IV), she said. To estimate the prevalence and odds of taking a potentially harmful supplement by chronic kidney disease status, "we used multivariate logistic regression weighted to the U.S. population," she said at the meeting sponsored by the American Society of Nephrology.

More than half (52.4%) of survey participants reported taking any dietary supplement, among which 15.3% reported taking a supplement containing at least one of the potentially harmful herbs, Dr. Grubbs reported. Although the crude estimated prevalence of individuals taking any dietary supplement increased with greater chronic kidney disease severity – with reported use by 51.4% of individuals with no kidney disease, 49.1% of those with stage I/II disease, and 65.8% of those with stage III/IV disease – it decreased among those taking a potentially harmful supplement – with reported use by 16.1%, 13.0%, and 10.0%, respectively, she said.

"Nearly 1 in 10 adult Americans takes a dietary supplement that is potentially harmful to the kidneys."

After adjusting for demographics, comorbid disease, and health care visits, however, "chronic kidney disease status was not a significant determinant of taking any supplement or of taking a potentially harmful supplement," Dr. Grubbs said.

The fact that so many individuals are taking supplements with ingredients that can be harmful to the kidneys is especially problematic, she stressed, "because many people with advanced kidney disease – up to 10% – are not aware that they have kidney disease." Further, she noted, the list of potentially harmful supplements may not be exhaustive, and because the supplements are not regulated as drugs, the amounts of the ingredients in question are unknown and thus may be more harmful than anticipated.

Until policy makers can be convinced to update the regulatory standards for dietary supplements, the onus for protecting patients is on physicians and on the patients themselves. "We have to educate ourselves about dietary supplements and ask patients about everything they are taking, and we have to educate our patients [about kidney disease] and the possibility of [supplements] doing more harm than good," Dr. Grubbs said.

Dr. Grubbs reported having no financial conflicts of interest.

Major Finding: Six years after gastric bypass surgery, the rate of diabetes remission in a cohort of morbidly obese patients was 75%, compared with 1% among those who did not undergo the procedure. The average weight loss from baseline was 28%.

Data Source: Longitudinal controlled prospective study evaluating the long-term weight and health outcomes of gastric bypass surgery in 418 morbidly obese patients.

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

ORLANDO – Cardiometabolic improvements following gastric bypass surgery persist over time, according to findings from the first prospective, long-term controlled trial to focus on gastric bypass patients.

After 6 years of follow-up, patients in the Utah Obesity Study who underwent the bariatric procedure maintained significant total weight loss and significant improvements in cardiovascular and metabolic measures and other disease end points relative to severely obese patients in the control group who did not undergo the surgery, according to Dr. Ted D. Adams of the University of Utah in Salt Lake City.

Of the 1,156 morbidly obese subjects enrolled in the study, 418 underwent gastric bypass surgery; 417 sought the procedure but were unable to have it, primarily because of lack of health insurance; and 321 were randomly selected as community controls from the Utah Health Family Tree program.

All of the participants underwent physical examinations and health evaluations at baseline, 2 years, and 6 years, including a physician interview and detailed medical history; resting electro- and echocardiograms; a submaximal exercise treadmill test and electrocardiogram; pulmonary function; limited polysomnography; resting metabolic rate; anthropometry; resting and exercise blood pressure; comprehensive blood chemistry; urinalysis; and dietary, quality of life, and physical activity questionnaires, Dr. Adams stated, noting that the 6-year follow-up was “excellent,” at 97%.

“In the surgical group, nearly all of the clinical measures improved significantly between the baseline and 2-year exams, and they remained significantly improved, compared with baseline at 6 years,” Dr. Adams said. In contrast, he noted, “the clinical variables in the combined control groups changed minimally if at all over the 6-year period.”

With respect to weight loss, the total weight reduction from baseline in the surgery group was 35% at 2 years and 28% at 6 years, while the average weight loss in the nonsurgical control subjects was negligible, Dr. Adams reported.

Further, the rate of diabetes remission at 6 years was 75% in the surgical group and 1% in the combined controls, and the incidence of diabetes in the surgical and control groups at 6 years was 2% and 16%, respectively, he said.

Cardiac morphology measures were also significantly improved at 6 months in the surgical group, Dr. Adams said. Echocardiography showed reduced left atrial volume and left ventricular mass, improvements that could potentially lead to reduction in obesity-related heart failure over time, he pointed out. The left atrial volume increased in the control group. Significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance were maintained at 6 years in the surgical group, as were higher levels of high-density lipoprotein cholesterol, he said.

The findings complement other cohort studies in bariatric surgery, Dr. Adams stated.

The cohort will continue to be followed to provide additional insight in the long-term durability of the improvements, he said.

Major Finding: Six years after gastric bypass surgery, the rate of diabetes remission in a cohort of morbidly obese patients was 75%, compared with 1% among those who did not undergo the procedure. The average weight loss from baseline was 28%.

Data Source: Longitudinal controlled prospective study evaluating the long-term weight and health outcomes of gastric bypass surgery in 418 morbidly obese patients.

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

ORLANDO – Cardiometabolic improvements following gastric bypass surgery persist over time, according to findings from the first prospective, long-term controlled trial to focus on gastric bypass patients.

After 6 years of follow-up, patients in the Utah Obesity Study who underwent the bariatric procedure maintained significant total weight loss and significant improvements in cardiovascular and metabolic measures and other disease end points relative to severely obese patients in the control group who did not undergo the surgery, according to Dr. Ted D. Adams of the University of Utah in Salt Lake City.

Of the 1,156 morbidly obese subjects enrolled in the study, 418 underwent gastric bypass surgery; 417 sought the procedure but were unable to have it, primarily because of lack of health insurance; and 321 were randomly selected as community controls from the Utah Health Family Tree program.

All of the participants underwent physical examinations and health evaluations at baseline, 2 years, and 6 years, including a physician interview and detailed medical history; resting electro- and echocardiograms; a submaximal exercise treadmill test and electrocardiogram; pulmonary function; limited polysomnography; resting metabolic rate; anthropometry; resting and exercise blood pressure; comprehensive blood chemistry; urinalysis; and dietary, quality of life, and physical activity questionnaires, Dr. Adams stated, noting that the 6-year follow-up was “excellent,” at 97%.

“In the surgical group, nearly all of the clinical measures improved significantly between the baseline and 2-year exams, and they remained significantly improved, compared with baseline at 6 years,” Dr. Adams said. In contrast, he noted, “the clinical variables in the combined control groups changed minimally if at all over the 6-year period.”

With respect to weight loss, the total weight reduction from baseline in the surgery group was 35% at 2 years and 28% at 6 years, while the average weight loss in the nonsurgical control subjects was negligible, Dr. Adams reported.

Further, the rate of diabetes remission at 6 years was 75% in the surgical group and 1% in the combined controls, and the incidence of diabetes in the surgical and control groups at 6 years was 2% and 16%, respectively, he said.

Cardiac morphology measures were also significantly improved at 6 months in the surgical group, Dr. Adams said. Echocardiography showed reduced left atrial volume and left ventricular mass, improvements that could potentially lead to reduction in obesity-related heart failure over time, he pointed out. The left atrial volume increased in the control group. Significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance were maintained at 6 years in the surgical group, as were higher levels of high-density lipoprotein cholesterol, he said.

The findings complement other cohort studies in bariatric surgery, Dr. Adams stated.

The cohort will continue to be followed to provide additional insight in the long-term durability of the improvements, he said.

Major Finding: Six years after gastric bypass surgery, the rate of diabetes remission in a cohort of morbidly obese patients was 75%, compared with 1% among those who did not undergo the procedure. The average weight loss from baseline was 28%.

Data Source: Longitudinal controlled prospective study evaluating the long-term weight and health outcomes of gastric bypass surgery in 418 morbidly obese patients.

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

ORLANDO – Cardiometabolic improvements following gastric bypass surgery persist over time, according to findings from the first prospective, long-term controlled trial to focus on gastric bypass patients.

After 6 years of follow-up, patients in the Utah Obesity Study who underwent the bariatric procedure maintained significant total weight loss and significant improvements in cardiovascular and metabolic measures and other disease end points relative to severely obese patients in the control group who did not undergo the surgery, according to Dr. Ted D. Adams of the University of Utah in Salt Lake City.

Of the 1,156 morbidly obese subjects enrolled in the study, 418 underwent gastric bypass surgery; 417 sought the procedure but were unable to have it, primarily because of lack of health insurance; and 321 were randomly selected as community controls from the Utah Health Family Tree program.

All of the participants underwent physical examinations and health evaluations at baseline, 2 years, and 6 years, including a physician interview and detailed medical history; resting electro- and echocardiograms; a submaximal exercise treadmill test and electrocardiogram; pulmonary function; limited polysomnography; resting metabolic rate; anthropometry; resting and exercise blood pressure; comprehensive blood chemistry; urinalysis; and dietary, quality of life, and physical activity questionnaires, Dr. Adams stated, noting that the 6-year follow-up was “excellent,” at 97%.

“In the surgical group, nearly all of the clinical measures improved significantly between the baseline and 2-year exams, and they remained significantly improved, compared with baseline at 6 years,” Dr. Adams said. In contrast, he noted, “the clinical variables in the combined control groups changed minimally if at all over the 6-year period.”

With respect to weight loss, the total weight reduction from baseline in the surgery group was 35% at 2 years and 28% at 6 years, while the average weight loss in the nonsurgical control subjects was negligible, Dr. Adams reported.

Further, the rate of diabetes remission at 6 years was 75% in the surgical group and 1% in the combined controls, and the incidence of diabetes in the surgical and control groups at 6 years was 2% and 16%, respectively, he said.

Cardiac morphology measures were also significantly improved at 6 months in the surgical group, Dr. Adams said. Echocardiography showed reduced left atrial volume and left ventricular mass, improvements that could potentially lead to reduction in obesity-related heart failure over time, he pointed out. The left atrial volume increased in the control group. Significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance were maintained at 6 years in the surgical group, as were higher levels of high-density lipoprotein cholesterol, he said.

The findings complement other cohort studies in bariatric surgery, Dr. Adams stated.

The cohort will continue to be followed to provide additional insight in the long-term durability of the improvements, he said.