Doug Brunk

SAN DIEGO — An estimated glomerular filtration rate of less than 30 mL/min is associated with malnutrition in all ages, while an estimated GFR between 30 and 59 mL/min is associated with malnutrition only in people older than age 60 years.

Those are key findings from a study that compared the prevalence of malnutrition in the elderly with that of younger age groups and that compared the risk of malnutrition using estimated GFR (eGFR) calculated by creatinine and cystatin C–based equations.

Researchers at Tufts Medical Center, Boston, examined the prevalence of malnutrition and its relationship to eGFR in 6,877 adults over the age of 20 years who participated in the National Health and Nutrition Examination Survey 1988-1994 (NHANES III).

Dr. Cindy Huang, a nephrology fellow at the medical center, reported that the prevalence of malnutrition increased with age in a stepwise fashion, from 9% in those aged 20-49 years to 12% in those aged 40-49; 15% in those 60-79, and 22% in those older than 80 years. An eGFR of less than 30 mL/min was associated with malnutrition in all ages, while an eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years, Dr. Huang said in a poster presented at the annual meeting of the American Society of Nephrology.

By estimating GFR by serum creatinine alone, the researchers found that a level of 90 mL/min or greater was associated with malnutrition in the elderly, most likely due to the presence of sarcopenia. The study was supported by a grant from the National Institutes of Health. Dr. Huang had no relevant financial disclosures to make.

An eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years.

Source DR. HUANG

SAN DIEGO — An estimated glomerular filtration rate of less than 30 mL/min is associated with malnutrition in all ages, while an estimated GFR between 30 and 59 mL/min is associated with malnutrition only in people older than age 60 years.

Those are key findings from a study that compared the prevalence of malnutrition in the elderly with that of younger age groups and that compared the risk of malnutrition using estimated GFR (eGFR) calculated by creatinine and cystatin C–based equations.

Researchers at Tufts Medical Center, Boston, examined the prevalence of malnutrition and its relationship to eGFR in 6,877 adults over the age of 20 years who participated in the National Health and Nutrition Examination Survey 1988-1994 (NHANES III).

Dr. Cindy Huang, a nephrology fellow at the medical center, reported that the prevalence of malnutrition increased with age in a stepwise fashion, from 9% in those aged 20-49 years to 12% in those aged 40-49; 15% in those 60-79, and 22% in those older than 80 years. An eGFR of less than 30 mL/min was associated with malnutrition in all ages, while an eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years, Dr. Huang said in a poster presented at the annual meeting of the American Society of Nephrology.

By estimating GFR by serum creatinine alone, the researchers found that a level of 90 mL/min or greater was associated with malnutrition in the elderly, most likely due to the presence of sarcopenia. The study was supported by a grant from the National Institutes of Health. Dr. Huang had no relevant financial disclosures to make.

An eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years.

Source DR. HUANG

SAN DIEGO — An estimated glomerular filtration rate of less than 30 mL/min is associated with malnutrition in all ages, while an estimated GFR between 30 and 59 mL/min is associated with malnutrition only in people older than age 60 years.

Those are key findings from a study that compared the prevalence of malnutrition in the elderly with that of younger age groups and that compared the risk of malnutrition using estimated GFR (eGFR) calculated by creatinine and cystatin C–based equations.

Researchers at Tufts Medical Center, Boston, examined the prevalence of malnutrition and its relationship to eGFR in 6,877 adults over the age of 20 years who participated in the National Health and Nutrition Examination Survey 1988-1994 (NHANES III).

Dr. Cindy Huang, a nephrology fellow at the medical center, reported that the prevalence of malnutrition increased with age in a stepwise fashion, from 9% in those aged 20-49 years to 12% in those aged 40-49; 15% in those 60-79, and 22% in those older than 80 years. An eGFR of less than 30 mL/min was associated with malnutrition in all ages, while an eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years, Dr. Huang said in a poster presented at the annual meeting of the American Society of Nephrology.

By estimating GFR by serum creatinine alone, the researchers found that a level of 90 mL/min or greater was associated with malnutrition in the elderly, most likely due to the presence of sarcopenia. The study was supported by a grant from the National Institutes of Health. Dr. Huang had no relevant financial disclosures to make.

An eGFR between 30 and 59 mL/min was associated with malnutrition only in people over age 60 years.

Source DR. HUANG

SAN DIEGO — Breast cancer survivors take an average of eight medications or supplements, results from a survey of nearly 400 women showed.

“This study shows that there is a need to evaluate medications women are taking prior to the start of cancer treatment to promote discussion and education about drug-drug interactions that can impact treatment,” Julie L. Otte, Ph.D., said in an interview after her poster presentation at the annual meeting of the North American Menopause Society.

The majority of research has focused on diseases and medications that are related to the prevalence of cancer, said Dr. Otte, a nurse who is a postdoctoral fellow focusing on behavioral oncology at Indiana University School of Nursing, Indianapolis. “However, there is little research in the field of pharmacogenetics regarding drug-drug interactions and cancer treatment and survivorship,” she said.

To investigate the association, she and her associates reviewed prescription, herbal, and over-the-counter medications reported in baseline questionnaire data from the COBRA (Consortium on Breast Cancer Pharmacogenomics) randomized clinical trial that evaluated the pharmacogenetics and toxicities of exemestane and letrozole for the treatment of breast cancer. The sample included 389 female breast cancer survivors with a mean age of 59 years and a mean body mass index of 37 kg/m

The top five noncancer comorbid conditions reported by the study participants were drug allergies (50%), high or low blood pressure (41%), high cholesterol (38%), a history of bone fracture (34%), and arthritis (29%).

The women reported that they were taking an average of eight medications or supplements per day. The five most common therapeutic categories represented were vitamins and herbal supplements (39%), cardiac drugs (16%), medications for pain and inflammation (13%), other (9%), and drugs for psychological conditions (6%).

“Although we expected the number of comorbid conditions to increase with age, requiring several prescription medications, it was interesting that the majority of medications reported were over-the-counter” herbals or supplements, and not prescriptions, Dr. Otte commented. Because these data were collected before the patients started a clinical trial, it is unclear whether patients would divulge the same information to their practitioners. The extent of polypharmacy is unclear.

“All of these questions prompt the need for further investigation and study to better educate patients on the possible harm of certain drug interactions,” Dr. Otte said.

She noted that there was potential for underreporting of prescription and over-the-counter medications by some participants.

Dr. Otte reported that she had no conflicts of interest. The study was funded by the National Cancer Institute.

SAN DIEGO — Breast cancer survivors take an average of eight medications or supplements, results from a survey of nearly 400 women showed.

“This study shows that there is a need to evaluate medications women are taking prior to the start of cancer treatment to promote discussion and education about drug-drug interactions that can impact treatment,” Julie L. Otte, Ph.D., said in an interview after her poster presentation at the annual meeting of the North American Menopause Society.

The majority of research has focused on diseases and medications that are related to the prevalence of cancer, said Dr. Otte, a nurse who is a postdoctoral fellow focusing on behavioral oncology at Indiana University School of Nursing, Indianapolis. “However, there is little research in the field of pharmacogenetics regarding drug-drug interactions and cancer treatment and survivorship,” she said.

To investigate the association, she and her associates reviewed prescription, herbal, and over-the-counter medications reported in baseline questionnaire data from the COBRA (Consortium on Breast Cancer Pharmacogenomics) randomized clinical trial that evaluated the pharmacogenetics and toxicities of exemestane and letrozole for the treatment of breast cancer. The sample included 389 female breast cancer survivors with a mean age of 59 years and a mean body mass index of 37 kg/m

The top five noncancer comorbid conditions reported by the study participants were drug allergies (50%), high or low blood pressure (41%), high cholesterol (38%), a history of bone fracture (34%), and arthritis (29%).

The women reported that they were taking an average of eight medications or supplements per day. The five most common therapeutic categories represented were vitamins and herbal supplements (39%), cardiac drugs (16%), medications for pain and inflammation (13%), other (9%), and drugs for psychological conditions (6%).

“Although we expected the number of comorbid conditions to increase with age, requiring several prescription medications, it was interesting that the majority of medications reported were over-the-counter” herbals or supplements, and not prescriptions, Dr. Otte commented. Because these data were collected before the patients started a clinical trial, it is unclear whether patients would divulge the same information to their practitioners. The extent of polypharmacy is unclear.

“All of these questions prompt the need for further investigation and study to better educate patients on the possible harm of certain drug interactions,” Dr. Otte said.

She noted that there was potential for underreporting of prescription and over-the-counter medications by some participants.

Dr. Otte reported that she had no conflicts of interest. The study was funded by the National Cancer Institute.

SAN DIEGO — Breast cancer survivors take an average of eight medications or supplements, results from a survey of nearly 400 women showed.

“This study shows that there is a need to evaluate medications women are taking prior to the start of cancer treatment to promote discussion and education about drug-drug interactions that can impact treatment,” Julie L. Otte, Ph.D., said in an interview after her poster presentation at the annual meeting of the North American Menopause Society.

The majority of research has focused on diseases and medications that are related to the prevalence of cancer, said Dr. Otte, a nurse who is a postdoctoral fellow focusing on behavioral oncology at Indiana University School of Nursing, Indianapolis. “However, there is little research in the field of pharmacogenetics regarding drug-drug interactions and cancer treatment and survivorship,” she said.

To investigate the association, she and her associates reviewed prescription, herbal, and over-the-counter medications reported in baseline questionnaire data from the COBRA (Consortium on Breast Cancer Pharmacogenomics) randomized clinical trial that evaluated the pharmacogenetics and toxicities of exemestane and letrozole for the treatment of breast cancer. The sample included 389 female breast cancer survivors with a mean age of 59 years and a mean body mass index of 37 kg/m

The top five noncancer comorbid conditions reported by the study participants were drug allergies (50%), high or low blood pressure (41%), high cholesterol (38%), a history of bone fracture (34%), and arthritis (29%).

The women reported that they were taking an average of eight medications or supplements per day. The five most common therapeutic categories represented were vitamins and herbal supplements (39%), cardiac drugs (16%), medications for pain and inflammation (13%), other (9%), and drugs for psychological conditions (6%).

“Although we expected the number of comorbid conditions to increase with age, requiring several prescription medications, it was interesting that the majority of medications reported were over-the-counter” herbals or supplements, and not prescriptions, Dr. Otte commented. Because these data were collected before the patients started a clinical trial, it is unclear whether patients would divulge the same information to their practitioners. The extent of polypharmacy is unclear.

“All of these questions prompt the need for further investigation and study to better educate patients on the possible harm of certain drug interactions,” Dr. Otte said.

She noted that there was potential for underreporting of prescription and over-the-counter medications by some participants.

Dr. Otte reported that she had no conflicts of interest. The study was funded by the National Cancer Institute.

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif. She and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H). The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning and in the subscale aspects of pleasure, desire/frequency and desire/interest; the number who were orgasmic was also lower among those who had bilateral oophorectomy.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

Dr. Plourde acknowledged that the small sample size was a limitation of the study. She disclosed no conflicts of interest.

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif. She and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H). The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning and in the subscale aspects of pleasure, desire/frequency and desire/interest; the number who were orgasmic was also lower among those who had bilateral oophorectomy.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

Dr. Plourde acknowledged that the small sample size was a limitation of the study. She disclosed no conflicts of interest.

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif. She and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H). The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning and in the subscale aspects of pleasure, desire/frequency and desire/interest; the number who were orgasmic was also lower among those who had bilateral oophorectomy.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

Dr. Plourde acknowledged that the small sample size was a limitation of the study. She disclosed no conflicts of interest.

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

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

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford of the United Kingdom Renal Registry, Bristol, England.

In what he said is the largest multicenter study of its kind in the United Kingdom, Dr. Ford and his associates evaluated the electronic medical records of 1,823 patients who underwent renal dialysis at seven centers between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months prior to the commencement of dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin over that period.

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

Dr. Ford reported that he had no relevant financial conflicts to disclose.

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

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

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford of the United Kingdom Renal Registry, Bristol, England.

In what he said is the largest multicenter study of its kind in the United Kingdom, Dr. Ford and his associates evaluated the electronic medical records of 1,823 patients who underwent renal dialysis at seven centers between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months prior to the commencement of dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin over that period.

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

Dr. Ford reported that he had no relevant financial conflicts to disclose.

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

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

“This reiterates what we know about patients with diabetic nephropathy—that they do have a tendency to have more anemia than patients with nondiabetic renal diseases,” said Dr. Ford of the United Kingdom Renal Registry, Bristol, England.

In what he said is the largest multicenter study of its kind in the United Kingdom, Dr. Ford and his associates evaluated the electronic medical records of 1,823 patients who underwent renal dialysis at seven centers between 2001 and 2006. They extracted data at time points 0, 1, 2, 3, 4, 5, 6, and 12 months prior to the commencement of dialysis and used a quadratic multilevel model to estimate the average pattern of decline in hemoglobin over that period.

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

Dr. Ford reported that he had no relevant financial conflicts to disclose.

SAN FRANCISCO — Patients with Clostridium difficile infection who were treated with the novel macrocylic antibiotic fidaxomicin had a 45% lower rate of recurrence, compared with those who received vancomycin.

“It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies,” Dr. Yoav Golan said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. “It's only twice a day dosing versus three and four times a day for metronidazole and vancomycin. Also, it seems to have a much smaller impact on emergence of resistance among gut pathogens.”

The analysis involved 432 patients in a multicenter, randomized trial to compare fidaxomicin, 200 mg every 12 hours, with vancomycin, 125 mg every 6 hours for 10 days, in patients with C. difficile. The mean age of patients was 62 years.

Fidaxomicin (Dificid), a minimally absorbed, narrow spectrum antibiotic with limited impact on gut flora, was developed by Optimer Pharmaceuticals, which sponsored the trial. Dr. Golan disclosed that his relationship with Optimer is limited to functioning as an investigator in the fidaxomicin clinical trials. Pamela Sears, Ph.D., executive director of biology and preclinical trials at Optimer, expects the company to file for new drug approval with the Food and Drug Administration by early 2011.

Overall, recurrence of diarrhea and positive toxin within 4 weeks after the end of therapy occurred in 19% of patients. The rate was significantly lower among the 211 patients in the fidaxomicin group (13%) than among the 221 patients in the vancomycin group (24%). This represented a relative reduction of 45% with fidaxomicin, compared with vancomycin.

Recurrence rates were highest in patients aged 75 years and older (31%) and in those aged 65–74 years (18%), and in those who were hospitalized (22% vs. 15% in outpatients).

Of the 81 patients with recurrent C. difficile, recurrence developed later in patients who took fidaxomicin. For example, 25% of patients in the fidaxomicin group had recurrence within 10 days after initial treatment completion vs. 57% of patients in the vancomycin group, while 36% of patients in the fidaxomicin group developed recurrence within 21–30 days after initial treatment vs. 15% of patients in the vancomycin group.

The recurrence rate was significantly lower for patients in the fidaxomicin group who had not received any C. difficile infection-active antibiotics 24 hours prior to study enrollment (11%, compared with a rate of 24% for their counterparts in the vancomycin group). This finding suggests the potential for a high clinical benefit for fidaxomicin when used as a first-line therapy, said Dr. Golan, assistant professor of medicine at Tufts Medical Center, Boston.

“The future for treating C. diff. is [to use] very narrow spectrum antibiotics, compared to the very broad spectrum antibiotics we've been using,” he concluded.

'It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies.'

Source DR. GOLAN

SAN FRANCISCO — Patients with Clostridium difficile infection who were treated with the novel macrocylic antibiotic fidaxomicin had a 45% lower rate of recurrence, compared with those who received vancomycin.

“It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies,” Dr. Yoav Golan said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. “It's only twice a day dosing versus three and four times a day for metronidazole and vancomycin. Also, it seems to have a much smaller impact on emergence of resistance among gut pathogens.”

The analysis involved 432 patients in a multicenter, randomized trial to compare fidaxomicin, 200 mg every 12 hours, with vancomycin, 125 mg every 6 hours for 10 days, in patients with C. difficile. The mean age of patients was 62 years.

Fidaxomicin (Dificid), a minimally absorbed, narrow spectrum antibiotic with limited impact on gut flora, was developed by Optimer Pharmaceuticals, which sponsored the trial. Dr. Golan disclosed that his relationship with Optimer is limited to functioning as an investigator in the fidaxomicin clinical trials. Pamela Sears, Ph.D., executive director of biology and preclinical trials at Optimer, expects the company to file for new drug approval with the Food and Drug Administration by early 2011.

Overall, recurrence of diarrhea and positive toxin within 4 weeks after the end of therapy occurred in 19% of patients. The rate was significantly lower among the 211 patients in the fidaxomicin group (13%) than among the 221 patients in the vancomycin group (24%). This represented a relative reduction of 45% with fidaxomicin, compared with vancomycin.

Recurrence rates were highest in patients aged 75 years and older (31%) and in those aged 65–74 years (18%), and in those who were hospitalized (22% vs. 15% in outpatients).

Of the 81 patients with recurrent C. difficile, recurrence developed later in patients who took fidaxomicin. For example, 25% of patients in the fidaxomicin group had recurrence within 10 days after initial treatment completion vs. 57% of patients in the vancomycin group, while 36% of patients in the fidaxomicin group developed recurrence within 21–30 days after initial treatment vs. 15% of patients in the vancomycin group.

The recurrence rate was significantly lower for patients in the fidaxomicin group who had not received any C. difficile infection-active antibiotics 24 hours prior to study enrollment (11%, compared with a rate of 24% for their counterparts in the vancomycin group). This finding suggests the potential for a high clinical benefit for fidaxomicin when used as a first-line therapy, said Dr. Golan, assistant professor of medicine at Tufts Medical Center, Boston.

“The future for treating C. diff. is [to use] very narrow spectrum antibiotics, compared to the very broad spectrum antibiotics we've been using,” he concluded.

'It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies.'

Source DR. GOLAN

SAN FRANCISCO — Patients with Clostridium difficile infection who were treated with the novel macrocylic antibiotic fidaxomicin had a 45% lower rate of recurrence, compared with those who received vancomycin.

“It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies,” Dr. Yoav Golan said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. “It's only twice a day dosing versus three and four times a day for metronidazole and vancomycin. Also, it seems to have a much smaller impact on emergence of resistance among gut pathogens.”

The analysis involved 432 patients in a multicenter, randomized trial to compare fidaxomicin, 200 mg every 12 hours, with vancomycin, 125 mg every 6 hours for 10 days, in patients with C. difficile. The mean age of patients was 62 years.

Fidaxomicin (Dificid), a minimally absorbed, narrow spectrum antibiotic with limited impact on gut flora, was developed by Optimer Pharmaceuticals, which sponsored the trial. Dr. Golan disclosed that his relationship with Optimer is limited to functioning as an investigator in the fidaxomicin clinical trials. Pamela Sears, Ph.D., executive director of biology and preclinical trials at Optimer, expects the company to file for new drug approval with the Food and Drug Administration by early 2011.

Overall, recurrence of diarrhea and positive toxin within 4 weeks after the end of therapy occurred in 19% of patients. The rate was significantly lower among the 211 patients in the fidaxomicin group (13%) than among the 221 patients in the vancomycin group (24%). This represented a relative reduction of 45% with fidaxomicin, compared with vancomycin.

Recurrence rates were highest in patients aged 75 years and older (31%) and in those aged 65–74 years (18%), and in those who were hospitalized (22% vs. 15% in outpatients).

Of the 81 patients with recurrent C. difficile, recurrence developed later in patients who took fidaxomicin. For example, 25% of patients in the fidaxomicin group had recurrence within 10 days after initial treatment completion vs. 57% of patients in the vancomycin group, while 36% of patients in the fidaxomicin group developed recurrence within 21–30 days after initial treatment vs. 15% of patients in the vancomycin group.

The recurrence rate was significantly lower for patients in the fidaxomicin group who had not received any C. difficile infection-active antibiotics 24 hours prior to study enrollment (11%, compared with a rate of 24% for their counterparts in the vancomycin group). This finding suggests the potential for a high clinical benefit for fidaxomicin when used as a first-line therapy, said Dr. Golan, assistant professor of medicine at Tufts Medical Center, Boston.

“The future for treating C. diff. is [to use] very narrow spectrum antibiotics, compared to the very broad spectrum antibiotics we've been using,” he concluded.

'It's encouraging because fidaxomicin is an easier drug to take compared with the current therapies.'

Source DR. GOLAN

SAN FRANCISCO — Fidaxomicin appears to be just as safe as vancomycin for the treatment of Clostridium difficile infection, results from a multicenter randomized trial showed.

The finding comes from the first phase III study of fidaxomicin (Dificid), a first-in-class macrocyclic antibiotic for the treatment of C. difficile. A second phase III trial that is underway is expected to be completed by the end of the year, Pamela Sears, Ph.D., said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The drug's safety profile is “very similar to oral vancomycin, which is a very safe drug,” said Dr. Sears, executive director of biology and preclinical trials at Optimer Pharmaceuticals Inc., San Diego, which developed the drug.

Dr. Sears and her associates said fidaxomicin has “potent bactericidal activity against C. difficile infection with a prolonged postantibiotic effect but minimal activity against much of the other commensal gut flora. The narrow spectrum of activity allows fidaxomicin to kill C. difficile while sparing much of the normal gut flora. Importantly, fidaxomicin is also minimally absorbed from the gastrointestinal tract.”

In a multicenter trial supported by Optimer, the researchers compared two regimens for C. difficile: fidaxomicin 200 mg twice a day (300 patients) and vancomycin 125 mg four times a day (323 patients). Both agents were taken for 10 days. The mean age of the patients was 62 years. At baseline and after 10 days of therapy, the researchers collected plasma and urine samples, obtained 12-lead electrocardiograms, and conducted physical exams.

Any treatment-emergent event occurred in 62% of patients in the fidaxomicin group and in 60% of patients in the vancomycin group. Gastrointestinal disorders were most common (25% vs. 22%), followed by infections (21% vs. 20%, primarily urinary tract infections and pneumonia) and general disorders and administration site conditions (15% vs. 16%, primarily fever, chills, edema, and fatigue).

The incidence of serious adverse events also was similar between groups: 25% in the fidaxomicin group, compared with 24% among the vancomycin group. The most common serious adverse events were infections, including C. difficile, pneumonia, sepsis, or bacteremia (7% vs. 9%, respectively), and GI disorders (4% vs. 3%). Fewer than 3% of patients in both groups developed abnormal liver, blood, and renal tests while on therapy, and mortality was similar in both groups (5% vs. 7%). No death was considered to be related to the study drug.

A limitation of the study was that it did not compare fidaxomicin with metronidazole. For C. difficile, vancomycin “appears to be the marketed compound that performs the best, but most people use metronidazole. We may explore that comparison in phase IV,” she said.

Dr. Sears expects Optimer to file for new drug approval with the Food and Drug Administration by early 2011.

Any treatment-emergent event occurred in 62% of patients on fidaxomicin and 60% of those on vancomycin.

Source DR. SEARS

SAN FRANCISCO — Fidaxomicin appears to be just as safe as vancomycin for the treatment of Clostridium difficile infection, results from a multicenter randomized trial showed.

The finding comes from the first phase III study of fidaxomicin (Dificid), a first-in-class macrocyclic antibiotic for the treatment of C. difficile. A second phase III trial that is underway is expected to be completed by the end of the year, Pamela Sears, Ph.D., said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The drug's safety profile is “very similar to oral vancomycin, which is a very safe drug,” said Dr. Sears, executive director of biology and preclinical trials at Optimer Pharmaceuticals Inc., San Diego, which developed the drug.

Dr. Sears and her associates said fidaxomicin has “potent bactericidal activity against C. difficile infection with a prolonged postantibiotic effect but minimal activity against much of the other commensal gut flora. The narrow spectrum of activity allows fidaxomicin to kill C. difficile while sparing much of the normal gut flora. Importantly, fidaxomicin is also minimally absorbed from the gastrointestinal tract.”

In a multicenter trial supported by Optimer, the researchers compared two regimens for C. difficile: fidaxomicin 200 mg twice a day (300 patients) and vancomycin 125 mg four times a day (323 patients). Both agents were taken for 10 days. The mean age of the patients was 62 years. At baseline and after 10 days of therapy, the researchers collected plasma and urine samples, obtained 12-lead electrocardiograms, and conducted physical exams.

Any treatment-emergent event occurred in 62% of patients in the fidaxomicin group and in 60% of patients in the vancomycin group. Gastrointestinal disorders were most common (25% vs. 22%), followed by infections (21% vs. 20%, primarily urinary tract infections and pneumonia) and general disorders and administration site conditions (15% vs. 16%, primarily fever, chills, edema, and fatigue).

The incidence of serious adverse events also was similar between groups: 25% in the fidaxomicin group, compared with 24% among the vancomycin group. The most common serious adverse events were infections, including C. difficile, pneumonia, sepsis, or bacteremia (7% vs. 9%, respectively), and GI disorders (4% vs. 3%). Fewer than 3% of patients in both groups developed abnormal liver, blood, and renal tests while on therapy, and mortality was similar in both groups (5% vs. 7%). No death was considered to be related to the study drug.

A limitation of the study was that it did not compare fidaxomicin with metronidazole. For C. difficile, vancomycin “appears to be the marketed compound that performs the best, but most people use metronidazole. We may explore that comparison in phase IV,” she said.

Dr. Sears expects Optimer to file for new drug approval with the Food and Drug Administration by early 2011.

Any treatment-emergent event occurred in 62% of patients on fidaxomicin and 60% of those on vancomycin.

Source DR. SEARS

SAN FRANCISCO — Fidaxomicin appears to be just as safe as vancomycin for the treatment of Clostridium difficile infection, results from a multicenter randomized trial showed.

The finding comes from the first phase III study of fidaxomicin (Dificid), a first-in-class macrocyclic antibiotic for the treatment of C. difficile. A second phase III trial that is underway is expected to be completed by the end of the year, Pamela Sears, Ph.D., said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The drug's safety profile is “very similar to oral vancomycin, which is a very safe drug,” said Dr. Sears, executive director of biology and preclinical trials at Optimer Pharmaceuticals Inc., San Diego, which developed the drug.

Dr. Sears and her associates said fidaxomicin has “potent bactericidal activity against C. difficile infection with a prolonged postantibiotic effect but minimal activity against much of the other commensal gut flora. The narrow spectrum of activity allows fidaxomicin to kill C. difficile while sparing much of the normal gut flora. Importantly, fidaxomicin is also minimally absorbed from the gastrointestinal tract.”

In a multicenter trial supported by Optimer, the researchers compared two regimens for C. difficile: fidaxomicin 200 mg twice a day (300 patients) and vancomycin 125 mg four times a day (323 patients). Both agents were taken for 10 days. The mean age of the patients was 62 years. At baseline and after 10 days of therapy, the researchers collected plasma and urine samples, obtained 12-lead electrocardiograms, and conducted physical exams.

Any treatment-emergent event occurred in 62% of patients in the fidaxomicin group and in 60% of patients in the vancomycin group. Gastrointestinal disorders were most common (25% vs. 22%), followed by infections (21% vs. 20%, primarily urinary tract infections and pneumonia) and general disorders and administration site conditions (15% vs. 16%, primarily fever, chills, edema, and fatigue).

The incidence of serious adverse events also was similar between groups: 25% in the fidaxomicin group, compared with 24% among the vancomycin group. The most common serious adverse events were infections, including C. difficile, pneumonia, sepsis, or bacteremia (7% vs. 9%, respectively), and GI disorders (4% vs. 3%). Fewer than 3% of patients in both groups developed abnormal liver, blood, and renal tests while on therapy, and mortality was similar in both groups (5% vs. 7%). No death was considered to be related to the study drug.

A limitation of the study was that it did not compare fidaxomicin with metronidazole. For C. difficile, vancomycin “appears to be the marketed compound that performs the best, but most people use metronidazole. We may explore that comparison in phase IV,” she said.

Dr. Sears expects Optimer to file for new drug approval with the Food and Drug Administration by early 2011.

Any treatment-emergent event occurred in 62% of patients on fidaxomicin and 60% of those on vancomycin.

Source DR. SEARS

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning, compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said in an interview during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif., with research interests in the biochemical and structural changes that arise from removal of reproductive organs.

“They're not really being apprised of the significance” before undergoing the procedure, she said.

Dr. Plourde and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H).

The latter measure was designed for the study to compare the changes in sexual response before and after surgery. The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning, as well as lower scores in the subscale aspects of pleasure, desire/frequency, and desire/interest.

The number of women who were orgasmic was also lower among those who had bilateral oophorectomy, the study found.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

“I redid all of the calculations to make sure that they were right, because the degree of significance between the two groups surprised me,” Dr. Plourde commented.

There were no statistically significant differences between the two groups of women in their rating of the importance of sex before and after surgery.

“The complexity and multifaceted nature of the human sexual response is demonstrated by the fact that not all the women who had their ovaries removed lost their interest in sex or ability to respond sexually, and not all of the women who retained their ovaries maintained their sexual functioning,” the study investigators wrote in their poster.

“These conflicting results indicate there are other factors that influence sexual functioning and need further research,” they said.

Dr. Plourde acknowledged that the small sample size was a limitation of the study.

She disclosed no financial conflicts of interest.

A related video is at www.youtube.com/InternalMedicineNews

Women are 'not really being apprised of the significance' before undergoing oophorectomy.

Source DR. PLOURDE

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning, compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said in an interview during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif., with research interests in the biochemical and structural changes that arise from removal of reproductive organs.

“They're not really being apprised of the significance” before undergoing the procedure, she said.

Dr. Plourde and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H).

The latter measure was designed for the study to compare the changes in sexual response before and after surgery. The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning, as well as lower scores in the subscale aspects of pleasure, desire/frequency, and desire/interest.

The number of women who were orgasmic was also lower among those who had bilateral oophorectomy, the study found.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

“I redid all of the calculations to make sure that they were right, because the degree of significance between the two groups surprised me,” Dr. Plourde commented.

There were no statistically significant differences between the two groups of women in their rating of the importance of sex before and after surgery.

“The complexity and multifaceted nature of the human sexual response is demonstrated by the fact that not all the women who had their ovaries removed lost their interest in sex or ability to respond sexually, and not all of the women who retained their ovaries maintained their sexual functioning,” the study investigators wrote in their poster.

“These conflicting results indicate there are other factors that influence sexual functioning and need further research,” they said.

Dr. Plourde acknowledged that the small sample size was a limitation of the study.

She disclosed no financial conflicts of interest.

A related video is at www.youtube.com/InternalMedicineNews

Women are 'not really being apprised of the significance' before undergoing oophorectomy.

Source DR. PLOURDE

SAN DIEGO — Women who underwent bilateral oophorectomy at the time of hysterectomy reported significantly decreased levels of sexual functioning, compared with women who underwent hysterectomy with ovarian conservation, results from a survey of 50 women showed.

The findings underscore the potential impact of prophylactic ovary removal on women's sexual functioning, Elizabeth Plourde, Ph.D., said in an interview during a poster session at the annual meeting of the North American Menopause Society.

“The potential for loss of ability to respond sexually is a very important consideration for women who are being advised to do prophylactic oophorectomy,” said Dr. Plourde, a psychologist in Irvine, Calif., with research interests in the biochemical and structural changes that arise from removal of reproductive organs.

“They're not really being apprised of the significance” before undergoing the procedure, she said.

Dr. Plourde and her associates asked 25 women who underwent hysterectomy with ovarian conservation and 25 women who underwent bilateral oophorohysterectomy to complete the Changes in Sexual Functioning Questionnaire–Female (CSFQ-F) and the Sexual Response Questionnaire–Hysterectomy (SRQ-H).

The latter measure was designed for the study to compare the changes in sexual response before and after surgery. The mean age of the respondents was 49 years.

Only women with functioning ovaries, based on their responses to a survey of menopause symptoms, were retained for the hysterectomy-only group, she said.

Compared with women who underwent a hysterectomy with ovarian conservation, those who underwent bilateral oophorectomy at the time of hysterectomy had significantly lower scores in total sexual functioning, as well as lower scores in the subscale aspects of pleasure, desire/frequency, and desire/interest.

The number of women who were orgasmic was also lower among those who had bilateral oophorectomy, the study found.

Significant interactions favoring the hysterectomy with ovarian conservation group were also detected before and after surgery in total sexual functioning scores and in the subscales of pleasure, desire/frequency, desire/interest, and orgasm/completion.

“I redid all of the calculations to make sure that they were right, because the degree of significance between the two groups surprised me,” Dr. Plourde commented.

There were no statistically significant differences between the two groups of women in their rating of the importance of sex before and after surgery.

“The complexity and multifaceted nature of the human sexual response is demonstrated by the fact that not all the women who had their ovaries removed lost their interest in sex or ability to respond sexually, and not all of the women who retained their ovaries maintained their sexual functioning,” the study investigators wrote in their poster.

“These conflicting results indicate there are other factors that influence sexual functioning and need further research,” they said.

Dr. Plourde acknowledged that the small sample size was a limitation of the study.

She disclosed no financial conflicts of interest.

A related video is at www.youtube.com/InternalMedicineNews

Women are 'not really being apprised of the significance' before undergoing oophorectomy.

Source DR. PLOURDE

SAN DIEGO — Following 2 years of treatment with ambrisentan for pulmonary arterial hypertension, patients with World Health Organization functional class I and II symptoms at baseline had a lower risk of clinical worsening and death, compared with those who had WHO class III and IV symptoms at baseline.

Patients in both subgroups also experienced improvements in 6-minute walk distance from their baseline rates.

Those are key findings from the longest-term study to date of ambrisentan (Letairis) in patients with pulmonary hypertension. The agent was approved in 2007 as a once-daily treatment for patients with WHO functional class II or III symptoms to improve exercise capacity and delay clinical worsening.

“This medication seems to work long term,” lead investigator Dr. Fernando Torres said in an interview during a poster session at an international conference of the American Thoracic Society. “Not only is it working at 2 years, but most of the patients are still on monotherapy. We did not have to add a second medication to keep them doing clinically well.”

Dr. Torres and his associates conducted a long-term extension study in 287 patients who participated in the Placebo-Controlled, Efficacy and Safety Study of Ambrisentan in Patients With Pulmonary Arterial Hypertension (ARIES)-1 and ARIES-2 trials. Patients who received ambrisentan in previous studies remained on the current dose, while patients who received placebo in previous studies were randomized to ambrisentan 5 mg or 10 mg daily.

At baseline, the mean age of the 287 patients was 50 years, and 82% of patients were female; 123 patients had WHO I and II symptoms, and 164 patients had WHO III and IV symptoms. By the second year, 20 patients with WHO I and II symptoms had discontinued the trial, as did 53 patients with WHO III and IV symptoms.

By year 2, 13% of patients with WHO I and II symptoms had no clinical worsening of disease, compared with 39% of patients with WHO III and IV symptoms, a difference that was statistically significant, reported Dr. Torres, director of the pulmonary hypertension program at the University of Texas Southwestern Medical Center, Dallas.

Patients with WHO I and II symptoms had more favorable long-term survival, compared with those who had WHO III and IV symptoms (95% vs. 83%), which was statistically significant.

The most common clinical worsening events were hospitalization for pulmonary arterial hypertension (9% in those with WHO I and II symptoms vs. 27% in those with WHO III and IV symptoms), the addition of prostanoid therapy (5% vs. 13%), and death (4% vs. 15%).

The most common adverse events resulting in death were right ventricular failure (1% in those patients with WHO I and II symptoms vs. 4% in those patients with WHO III and IV symptoms) and pulmonary hypertension (0% vs. 2%).

The majority of patients in both subgroups remained on monotherapy through year 2 (85% with WHO I and II symptoms, compared with 72% with WHO III and IV symptoms). “Most of these patients seem to be stable using just one medication,” Dr. Torres said.

He also reported that by year 2, the 6-minute walk distance was improved in both subgroups, and the change from baseline appeared to be slightly better for patients with WHO I and II symptoms at baseline.

A chief limitation of the study, Dr. Torres said, is that it lacked a placebo group, because it would be unethical to keep patients on placebo for that long.

He disclosed that he is a paid researcher, consultant, and adviser to the makers of Letairis, Gilead Sciences, which funded the study.

SAN DIEGO — Following 2 years of treatment with ambrisentan for pulmonary arterial hypertension, patients with World Health Organization functional class I and II symptoms at baseline had a lower risk of clinical worsening and death, compared with those who had WHO class III and IV symptoms at baseline.

Patients in both subgroups also experienced improvements in 6-minute walk distance from their baseline rates.

Those are key findings from the longest-term study to date of ambrisentan (Letairis) in patients with pulmonary hypertension. The agent was approved in 2007 as a once-daily treatment for patients with WHO functional class II or III symptoms to improve exercise capacity and delay clinical worsening.

“This medication seems to work long term,” lead investigator Dr. Fernando Torres said in an interview during a poster session at an international conference of the American Thoracic Society. “Not only is it working at 2 years, but most of the patients are still on monotherapy. We did not have to add a second medication to keep them doing clinically well.”

Dr. Torres and his associates conducted a long-term extension study in 287 patients who participated in the Placebo-Controlled, Efficacy and Safety Study of Ambrisentan in Patients With Pulmonary Arterial Hypertension (ARIES)-1 and ARIES-2 trials. Patients who received ambrisentan in previous studies remained on the current dose, while patients who received placebo in previous studies were randomized to ambrisentan 5 mg or 10 mg daily.

At baseline, the mean age of the 287 patients was 50 years, and 82% of patients were female; 123 patients had WHO I and II symptoms, and 164 patients had WHO III and IV symptoms. By the second year, 20 patients with WHO I and II symptoms had discontinued the trial, as did 53 patients with WHO III and IV symptoms.

By year 2, 13% of patients with WHO I and II symptoms had no clinical worsening of disease, compared with 39% of patients with WHO III and IV symptoms, a difference that was statistically significant, reported Dr. Torres, director of the pulmonary hypertension program at the University of Texas Southwestern Medical Center, Dallas.

Patients with WHO I and II symptoms had more favorable long-term survival, compared with those who had WHO III and IV symptoms (95% vs. 83%), which was statistically significant.

The most common clinical worsening events were hospitalization for pulmonary arterial hypertension (9% in those with WHO I and II symptoms vs. 27% in those with WHO III and IV symptoms), the addition of prostanoid therapy (5% vs. 13%), and death (4% vs. 15%).

The most common adverse events resulting in death were right ventricular failure (1% in those patients with WHO I and II symptoms vs. 4% in those patients with WHO III and IV symptoms) and pulmonary hypertension (0% vs. 2%).

The majority of patients in both subgroups remained on monotherapy through year 2 (85% with WHO I and II symptoms, compared with 72% with WHO III and IV symptoms). “Most of these patients seem to be stable using just one medication,” Dr. Torres said.

He also reported that by year 2, the 6-minute walk distance was improved in both subgroups, and the change from baseline appeared to be slightly better for patients with WHO I and II symptoms at baseline.

A chief limitation of the study, Dr. Torres said, is that it lacked a placebo group, because it would be unethical to keep patients on placebo for that long.

He disclosed that he is a paid researcher, consultant, and adviser to the makers of Letairis, Gilead Sciences, which funded the study.

SAN DIEGO — Following 2 years of treatment with ambrisentan for pulmonary arterial hypertension, patients with World Health Organization functional class I and II symptoms at baseline had a lower risk of clinical worsening and death, compared with those who had WHO class III and IV symptoms at baseline.

Patients in both subgroups also experienced improvements in 6-minute walk distance from their baseline rates.

Those are key findings from the longest-term study to date of ambrisentan (Letairis) in patients with pulmonary hypertension. The agent was approved in 2007 as a once-daily treatment for patients with WHO functional class II or III symptoms to improve exercise capacity and delay clinical worsening.

“This medication seems to work long term,” lead investigator Dr. Fernando Torres said in an interview during a poster session at an international conference of the American Thoracic Society. “Not only is it working at 2 years, but most of the patients are still on monotherapy. We did not have to add a second medication to keep them doing clinically well.”

Dr. Torres and his associates conducted a long-term extension study in 287 patients who participated in the Placebo-Controlled, Efficacy and Safety Study of Ambrisentan in Patients With Pulmonary Arterial Hypertension (ARIES)-1 and ARIES-2 trials. Patients who received ambrisentan in previous studies remained on the current dose, while patients who received placebo in previous studies were randomized to ambrisentan 5 mg or 10 mg daily.

At baseline, the mean age of the 287 patients was 50 years, and 82% of patients were female; 123 patients had WHO I and II symptoms, and 164 patients had WHO III and IV symptoms. By the second year, 20 patients with WHO I and II symptoms had discontinued the trial, as did 53 patients with WHO III and IV symptoms.

By year 2, 13% of patients with WHO I and II symptoms had no clinical worsening of disease, compared with 39% of patients with WHO III and IV symptoms, a difference that was statistically significant, reported Dr. Torres, director of the pulmonary hypertension program at the University of Texas Southwestern Medical Center, Dallas.

Patients with WHO I and II symptoms had more favorable long-term survival, compared with those who had WHO III and IV symptoms (95% vs. 83%), which was statistically significant.

The most common clinical worsening events were hospitalization for pulmonary arterial hypertension (9% in those with WHO I and II symptoms vs. 27% in those with WHO III and IV symptoms), the addition of prostanoid therapy (5% vs. 13%), and death (4% vs. 15%).

The most common adverse events resulting in death were right ventricular failure (1% in those patients with WHO I and II symptoms vs. 4% in those patients with WHO III and IV symptoms) and pulmonary hypertension (0% vs. 2%).

The majority of patients in both subgroups remained on monotherapy through year 2 (85% with WHO I and II symptoms, compared with 72% with WHO III and IV symptoms). “Most of these patients seem to be stable using just one medication,” Dr. Torres said.

He also reported that by year 2, the 6-minute walk distance was improved in both subgroups, and the change from baseline appeared to be slightly better for patients with WHO I and II symptoms at baseline.

A chief limitation of the study, Dr. Torres said, is that it lacked a placebo group, because it would be unethical to keep patients on placebo for that long.

He disclosed that he is a paid researcher, consultant, and adviser to the makers of Letairis, Gilead Sciences, which funded the study.

SAN DIEGO — The ability of vitamin D to reduce the risks of cardiovascular disease and cancer are about to be put to the test in a randomized, controlled study.

January will bring the launch of the vitamin D and omega-3 trial (VITAL), a 20,000-participant study that will examine whether daily dietary supplements of vitamin D (about 2,000 IU) or fish oil (about 1 g of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke.

Speaking at the annual meeting of the North American Menopause Society, Dr. Edward Giovannucci said that observational studies have validated vitamin D status as predictive of cardiovascular disease and cancer risks. The next step is therapeutic intervention with “various ranges of vitamin D. We need to know the dose-response better. We can learn a lot from intermediate end points such as inflammatory markers, but ultimately we need to look at hard end points such as cardiovascular disease and cancer.”

The best studies to date suggest that serum vitamin D levels of 30 ng/mL or more are optimal for reducing the risk of cardiovascular disease and cancer, said Dr. Giovannucci, professor of nutrition and epidemiology at Harvard School of Public Health, Boston.

“There is no credible evidence of any risk associated with this level of intake,” he said, but “we need to weigh benefits and risks” of vitamin D supplementation. Hypothetical associations between vitamin D deficiency and cardiovascular disease include increased levels of vascular calcification, vascular smooth cell proliferation, parathyroid hormone, tumor necrosis factor–alpha, and interleukin-6.

The research also could influence understanding of the pathophysiology of diseases, Dr. Giovannucci said. Elevated parathyroid hormone levels, for example, may contribute to hypertension and left ventricular hypertrophy.

In the Framingham Offspring Study, for example, a vitamin D level of 30 ng/mL or greater was associated with a 50% reduction in risk for a cardiovascular event (Circulation 2008;117:503-11). “The risk flattened off at vitamin D levels of 20-25 ng/mL,” he said.

In the Health Professionals Follow-up Study, a nested case-control study of myocardial infarction or fatal coronary heart disease, Dr. Giovannucci and his associates followed 454 cases and 900 controls for 10 years (Arch. Intern. Med. 2008;168:1174-80). After the investigators controlled for lifestyle factors, cardiovascular disease factors, lipids, and inflammatory markers, the relative risk for MI in those with serum vitamin D levels of 15 ng/mL or less was twice as high as in those with levels of 30 ng/mL or more.

“We also found a very strong association between cases of sudden death and low levels of vitamin D,” Dr. Giovannucci said.

A much larger cohort analysis, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, found strong associations between vitamin D status and all-cause and cardiovascular mortality (J. Endocrinol. Metab. 2008;93:3927-35). For example, about 35% of patients with vitamin D levels less than 15 ng/mL and 10% of those with levels greater than 30 ng/mL had died after nearly 8 years, he said.

As for vitamin D's effect on cancer risk, the evidence is strongest in colorectal cancer, he said. In breast cancer there have been some negative studies, but the Nurses' Health Study showed a link with borderline significance between vitamin D status andthreast cancer risk in women aged 60 and older (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991-7).

“There could possibly be an age gradient for vitamin D where the level might be more important for older women,” he commented.

Dr. Giovannucci said that he had no relevant financial disclosures.

'There could possibly be an age gradient for vitamin D where the level might be more important for older women.'

Source DR. GIOVANNUCCI

SAN DIEGO — The ability of vitamin D to reduce the risks of cardiovascular disease and cancer are about to be put to the test in a randomized, controlled study.

January will bring the launch of the vitamin D and omega-3 trial (VITAL), a 20,000-participant study that will examine whether daily dietary supplements of vitamin D (about 2,000 IU) or fish oil (about 1 g of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke.

Speaking at the annual meeting of the North American Menopause Society, Dr. Edward Giovannucci said that observational studies have validated vitamin D status as predictive of cardiovascular disease and cancer risks. The next step is therapeutic intervention with “various ranges of vitamin D. We need to know the dose-response better. We can learn a lot from intermediate end points such as inflammatory markers, but ultimately we need to look at hard end points such as cardiovascular disease and cancer.”

The best studies to date suggest that serum vitamin D levels of 30 ng/mL or more are optimal for reducing the risk of cardiovascular disease and cancer, said Dr. Giovannucci, professor of nutrition and epidemiology at Harvard School of Public Health, Boston.

“There is no credible evidence of any risk associated with this level of intake,” he said, but “we need to weigh benefits and risks” of vitamin D supplementation. Hypothetical associations between vitamin D deficiency and cardiovascular disease include increased levels of vascular calcification, vascular smooth cell proliferation, parathyroid hormone, tumor necrosis factor–alpha, and interleukin-6.

The research also could influence understanding of the pathophysiology of diseases, Dr. Giovannucci said. Elevated parathyroid hormone levels, for example, may contribute to hypertension and left ventricular hypertrophy.

In the Framingham Offspring Study, for example, a vitamin D level of 30 ng/mL or greater was associated with a 50% reduction in risk for a cardiovascular event (Circulation 2008;117:503-11). “The risk flattened off at vitamin D levels of 20-25 ng/mL,” he said.

In the Health Professionals Follow-up Study, a nested case-control study of myocardial infarction or fatal coronary heart disease, Dr. Giovannucci and his associates followed 454 cases and 900 controls for 10 years (Arch. Intern. Med. 2008;168:1174-80). After the investigators controlled for lifestyle factors, cardiovascular disease factors, lipids, and inflammatory markers, the relative risk for MI in those with serum vitamin D levels of 15 ng/mL or less was twice as high as in those with levels of 30 ng/mL or more.

“We also found a very strong association between cases of sudden death and low levels of vitamin D,” Dr. Giovannucci said.

A much larger cohort analysis, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, found strong associations between vitamin D status and all-cause and cardiovascular mortality (J. Endocrinol. Metab. 2008;93:3927-35). For example, about 35% of patients with vitamin D levels less than 15 ng/mL and 10% of those with levels greater than 30 ng/mL had died after nearly 8 years, he said.

As for vitamin D's effect on cancer risk, the evidence is strongest in colorectal cancer, he said. In breast cancer there have been some negative studies, but the Nurses' Health Study showed a link with borderline significance between vitamin D status andthreast cancer risk in women aged 60 and older (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991-7).

“There could possibly be an age gradient for vitamin D where the level might be more important for older women,” he commented.

Dr. Giovannucci said that he had no relevant financial disclosures.

'There could possibly be an age gradient for vitamin D where the level might be more important for older women.'

Source DR. GIOVANNUCCI

SAN DIEGO — The ability of vitamin D to reduce the risks of cardiovascular disease and cancer are about to be put to the test in a randomized, controlled study.

January will bring the launch of the vitamin D and omega-3 trial (VITAL), a 20,000-participant study that will examine whether daily dietary supplements of vitamin D (about 2,000 IU) or fish oil (about 1 g of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke.

Speaking at the annual meeting of the North American Menopause Society, Dr. Edward Giovannucci said that observational studies have validated vitamin D status as predictive of cardiovascular disease and cancer risks. The next step is therapeutic intervention with “various ranges of vitamin D. We need to know the dose-response better. We can learn a lot from intermediate end points such as inflammatory markers, but ultimately we need to look at hard end points such as cardiovascular disease and cancer.”

The best studies to date suggest that serum vitamin D levels of 30 ng/mL or more are optimal for reducing the risk of cardiovascular disease and cancer, said Dr. Giovannucci, professor of nutrition and epidemiology at Harvard School of Public Health, Boston.

“There is no credible evidence of any risk associated with this level of intake,” he said, but “we need to weigh benefits and risks” of vitamin D supplementation. Hypothetical associations between vitamin D deficiency and cardiovascular disease include increased levels of vascular calcification, vascular smooth cell proliferation, parathyroid hormone, tumor necrosis factor–alpha, and interleukin-6.

The research also could influence understanding of the pathophysiology of diseases, Dr. Giovannucci said. Elevated parathyroid hormone levels, for example, may contribute to hypertension and left ventricular hypertrophy.

In the Framingham Offspring Study, for example, a vitamin D level of 30 ng/mL or greater was associated with a 50% reduction in risk for a cardiovascular event (Circulation 2008;117:503-11). “The risk flattened off at vitamin D levels of 20-25 ng/mL,” he said.

In the Health Professionals Follow-up Study, a nested case-control study of myocardial infarction or fatal coronary heart disease, Dr. Giovannucci and his associates followed 454 cases and 900 controls for 10 years (Arch. Intern. Med. 2008;168:1174-80). After the investigators controlled for lifestyle factors, cardiovascular disease factors, lipids, and inflammatory markers, the relative risk for MI in those with serum vitamin D levels of 15 ng/mL or less was twice as high as in those with levels of 30 ng/mL or more.

“We also found a very strong association between cases of sudden death and low levels of vitamin D,” Dr. Giovannucci said.

A much larger cohort analysis, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, found strong associations between vitamin D status and all-cause and cardiovascular mortality (J. Endocrinol. Metab. 2008;93:3927-35). For example, about 35% of patients with vitamin D levels less than 15 ng/mL and 10% of those with levels greater than 30 ng/mL had died after nearly 8 years, he said.

As for vitamin D's effect on cancer risk, the evidence is strongest in colorectal cancer, he said. In breast cancer there have been some negative studies, but the Nurses' Health Study showed a link with borderline significance between vitamin D status andthreast cancer risk in women aged 60 and older (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991-7).

“There could possibly be an age gradient for vitamin D where the level might be more important for older women,” he commented.

Dr. Giovannucci said that he had no relevant financial disclosures.

'There could possibly be an age gradient for vitamin D where the level might be more important for older women.'

Source DR. GIOVANNUCCI

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been on many different medicines––they've been on oral or inhaled steroids and they're not responding––it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify the diagnosis of severe asthma.

Of the 152 patients, 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

Dr. Wenzel performs a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” Ms. Vitari explained. “If you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events, or stimuli.”

She acknowledged certain limitations of the study, including its single-center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been on many different medicines––they've been on oral or inhaled steroids and they're not responding––it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify the diagnosis of severe asthma.

Of the 152 patients, 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

Dr. Wenzel performs a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” Ms. Vitari explained. “If you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events, or stimuli.”

She acknowledged certain limitations of the study, including its single-center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been on many different medicines––they've been on oral or inhaled steroids and they're not responding––it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify the diagnosis of severe asthma.

Of the 152 patients, 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

Dr. Wenzel performs a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” Ms. Vitari explained. “If you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events, or stimuli.”

She acknowledged certain limitations of the study, including its single-center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.