M. Alexander Otto

BERNALILLO, N.M. – Intravaginal 5-fluorouracil might be a better option than watchful waiting for women with stage II cervical intraepithelial neoplasia, according to a small trial from the University of North Carolina at Chapel Hill.

Twenty-eight women aged 18-29 years with CIN 2 self-administered 2 g of 5% 5-fluorouracil cream (5-FU) intravaginally by applicator every 2 weeks for 16 weeks; 28 others were randomized to observation, the usual approach.

At 6 months, disease had regressed on colposcopic biopsy in 96% (27) of the 5-FU women, and 56% (15/27) were free of cervical human papilloma virus (HPV). Disease regressed in 57% (16) of the control group, and just 26% (7/27) were free of cervical HPV. The findings were statistically significant.

"The results from this study indicate that 5-FU is an effective medical therapy for CIN 2 in young women whose disease is being observed at 6-month intervals. Further investigation in women who are older or with a CIN 3 diagnosis is needed prior to considering this option in lieu of excisional or ablative management strategies," said lead investigator Dr. Lisa Rahangdale of the department of obstetrics and gynecology at the university.

"We need more data to make this a standard of care recommendation, but it has been successful in my practice," she said.

So long as they agree to avoid pregnancy while on the category X drug, "I’ve started offering women this option, particularly if they are not interested in an excisional procedure and are planning on childbearing; they are really excited to have a nonsurgical option. I also use it for women" with positive margins after excision, Dr. Rahangdale said. "Based on [a] previous study of HIV-positive women, this will help reduce their recurrence of disease," she added (Obstet. Gynecol. 1999;94:954-61).

About half of the women in the trial reported side effects, including irritation, discharge, and intermenstrual bleeding. One woman was withdrawn for possible ulceration; another, for vulvar erythema.

Even so, the women said the side effects didn’t interfere with their lives, and most would recommend 5-FU to a friend.

Topical formulations of the old chemotherapy drug were used in the past for genital warts and other HPV problems, but the drug was largely abandoned because of significant side effects with multiple doses per week. "I think our side effect profile is relatively favorable" because the dosing is biweekly, Dr. Rahangdale said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Most of the study subjects were white, and there were no statistically-significant between-group differences in HPV vaccination history, history of prior dysplasia, contraception or condom use, number of sexual partners, and other parameters. About a third of the treated women and a fifth of the untreated women reported having had at least one dose of HPV vaccine.

Dr. Rahangdale said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – Intravaginal 5-fluorouracil might be a better option than watchful waiting for women with stage II cervical intraepithelial neoplasia, according to a small trial from the University of North Carolina at Chapel Hill.

Twenty-eight women aged 18-29 years with CIN 2 self-administered 2 g of 5% 5-fluorouracil cream (5-FU) intravaginally by applicator every 2 weeks for 16 weeks; 28 others were randomized to observation, the usual approach.

At 6 months, disease had regressed on colposcopic biopsy in 96% (27) of the 5-FU women, and 56% (15/27) were free of cervical human papilloma virus (HPV). Disease regressed in 57% (16) of the control group, and just 26% (7/27) were free of cervical HPV. The findings were statistically significant.

"The results from this study indicate that 5-FU is an effective medical therapy for CIN 2 in young women whose disease is being observed at 6-month intervals. Further investigation in women who are older or with a CIN 3 diagnosis is needed prior to considering this option in lieu of excisional or ablative management strategies," said lead investigator Dr. Lisa Rahangdale of the department of obstetrics and gynecology at the university.

"We need more data to make this a standard of care recommendation, but it has been successful in my practice," she said.

So long as they agree to avoid pregnancy while on the category X drug, "I’ve started offering women this option, particularly if they are not interested in an excisional procedure and are planning on childbearing; they are really excited to have a nonsurgical option. I also use it for women" with positive margins after excision, Dr. Rahangdale said. "Based on [a] previous study of HIV-positive women, this will help reduce their recurrence of disease," she added (Obstet. Gynecol. 1999;94:954-61).

About half of the women in the trial reported side effects, including irritation, discharge, and intermenstrual bleeding. One woman was withdrawn for possible ulceration; another, for vulvar erythema.

Even so, the women said the side effects didn’t interfere with their lives, and most would recommend 5-FU to a friend.

Topical formulations of the old chemotherapy drug were used in the past for genital warts and other HPV problems, but the drug was largely abandoned because of significant side effects with multiple doses per week. "I think our side effect profile is relatively favorable" because the dosing is biweekly, Dr. Rahangdale said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Most of the study subjects were white, and there were no statistically-significant between-group differences in HPV vaccination history, history of prior dysplasia, contraception or condom use, number of sexual partners, and other parameters. About a third of the treated women and a fifth of the untreated women reported having had at least one dose of HPV vaccine.

Dr. Rahangdale said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – Intravaginal 5-fluorouracil might be a better option than watchful waiting for women with stage II cervical intraepithelial neoplasia, according to a small trial from the University of North Carolina at Chapel Hill.

Twenty-eight women aged 18-29 years with CIN 2 self-administered 2 g of 5% 5-fluorouracil cream (5-FU) intravaginally by applicator every 2 weeks for 16 weeks; 28 others were randomized to observation, the usual approach.

At 6 months, disease had regressed on colposcopic biopsy in 96% (27) of the 5-FU women, and 56% (15/27) were free of cervical human papilloma virus (HPV). Disease regressed in 57% (16) of the control group, and just 26% (7/27) were free of cervical HPV. The findings were statistically significant.

"The results from this study indicate that 5-FU is an effective medical therapy for CIN 2 in young women whose disease is being observed at 6-month intervals. Further investigation in women who are older or with a CIN 3 diagnosis is needed prior to considering this option in lieu of excisional or ablative management strategies," said lead investigator Dr. Lisa Rahangdale of the department of obstetrics and gynecology at the university.

"We need more data to make this a standard of care recommendation, but it has been successful in my practice," she said.

So long as they agree to avoid pregnancy while on the category X drug, "I’ve started offering women this option, particularly if they are not interested in an excisional procedure and are planning on childbearing; they are really excited to have a nonsurgical option. I also use it for women" with positive margins after excision, Dr. Rahangdale said. "Based on [a] previous study of HIV-positive women, this will help reduce their recurrence of disease," she added (Obstet. Gynecol. 1999;94:954-61).

About half of the women in the trial reported side effects, including irritation, discharge, and intermenstrual bleeding. One woman was withdrawn for possible ulceration; another, for vulvar erythema.

Even so, the women said the side effects didn’t interfere with their lives, and most would recommend 5-FU to a friend.

Topical formulations of the old chemotherapy drug were used in the past for genital warts and other HPV problems, but the drug was largely abandoned because of significant side effects with multiple doses per week. "I think our side effect profile is relatively favorable" because the dosing is biweekly, Dr. Rahangdale said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Most of the study subjects were white, and there were no statistically-significant between-group differences in HPV vaccination history, history of prior dysplasia, contraception or condom use, number of sexual partners, and other parameters. About a third of the treated women and a fifth of the untreated women reported having had at least one dose of HPV vaccine.

Dr. Rahangdale said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – Intravaginal high-dose metronidazole and miconazole may be better than metronidazole gel for keeping recurrent bacterial vaginosis at bay, according to the results of a small pilot study from Wayne State University in Detroit.

Eighteen women with refractory bacterial vaginosis (BV) were cured there with a 7-day course of the suppository, an ovule containing 750 mg metronidazole – far more than in a typical Metrogel (metronidazole gel) application – and 200 mg miconazole. The women were then switched to a twice-weekly maintenance regimen.

The 10 who returned for a checkup 1 month later were in remission, with no symptoms, no clue cells, a negative amine test result, and no more than one of four Amsel criteria. Nine of the 10 were still in remission at the 3-month checkup, at which time treatment was discontinued, senior author Dr. Jack Sobel reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although the regimen wasn’t compared directly with Metrogel maintenance, Dr. Sobel said that based on his earlier work, he’d expect twice-weekly Metrogel maintenance to keep about 6 or 7 women out of 10 in remission (Am. J. Obstet. Gynecol. 2006;194:1283-9).

The team used a product called Neo-Penotran Forte, a combination metronidazole/miconazole ovule not generally available in the United States. However, a similar suppository "can be made up by any compounding company," said Dr. Sobel, chief of Wayne State’s division of infectious diseases. The medication was well tolerated in the study.

Unfortunately and as is often the case with BV, "these patients recurred and recurred rapidly after stopping maintenance therapy," said coauthor and ob.gyn. Tina Aguin, also of Wayne State.

Six of nine patients relapsed within 3 months. "The bottom line is we are able to control people with intravaginal high-dose metronidazole maintenance, but we are not curing anyone," she said.

Dr. Aguin and Dr. Sobel said they had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – Intravaginal high-dose metronidazole and miconazole may be better than metronidazole gel for keeping recurrent bacterial vaginosis at bay, according to the results of a small pilot study from Wayne State University in Detroit.

Eighteen women with refractory bacterial vaginosis (BV) were cured there with a 7-day course of the suppository, an ovule containing 750 mg metronidazole – far more than in a typical Metrogel (metronidazole gel) application – and 200 mg miconazole. The women were then switched to a twice-weekly maintenance regimen.

The 10 who returned for a checkup 1 month later were in remission, with no symptoms, no clue cells, a negative amine test result, and no more than one of four Amsel criteria. Nine of the 10 were still in remission at the 3-month checkup, at which time treatment was discontinued, senior author Dr. Jack Sobel reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although the regimen wasn’t compared directly with Metrogel maintenance, Dr. Sobel said that based on his earlier work, he’d expect twice-weekly Metrogel maintenance to keep about 6 or 7 women out of 10 in remission (Am. J. Obstet. Gynecol. 2006;194:1283-9).

The team used a product called Neo-Penotran Forte, a combination metronidazole/miconazole ovule not generally available in the United States. However, a similar suppository "can be made up by any compounding company," said Dr. Sobel, chief of Wayne State’s division of infectious diseases. The medication was well tolerated in the study.

Unfortunately and as is often the case with BV, "these patients recurred and recurred rapidly after stopping maintenance therapy," said coauthor and ob.gyn. Tina Aguin, also of Wayne State.

Six of nine patients relapsed within 3 months. "The bottom line is we are able to control people with intravaginal high-dose metronidazole maintenance, but we are not curing anyone," she said.

Dr. Aguin and Dr. Sobel said they had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – Intravaginal high-dose metronidazole and miconazole may be better than metronidazole gel for keeping recurrent bacterial vaginosis at bay, according to the results of a small pilot study from Wayne State University in Detroit.

Eighteen women with refractory bacterial vaginosis (BV) were cured there with a 7-day course of the suppository, an ovule containing 750 mg metronidazole – far more than in a typical Metrogel (metronidazole gel) application – and 200 mg miconazole. The women were then switched to a twice-weekly maintenance regimen.

The 10 who returned for a checkup 1 month later were in remission, with no symptoms, no clue cells, a negative amine test result, and no more than one of four Amsel criteria. Nine of the 10 were still in remission at the 3-month checkup, at which time treatment was discontinued, senior author Dr. Jack Sobel reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although the regimen wasn’t compared directly with Metrogel maintenance, Dr. Sobel said that based on his earlier work, he’d expect twice-weekly Metrogel maintenance to keep about 6 or 7 women out of 10 in remission (Am. J. Obstet. Gynecol. 2006;194:1283-9).

The team used a product called Neo-Penotran Forte, a combination metronidazole/miconazole ovule not generally available in the United States. However, a similar suppository "can be made up by any compounding company," said Dr. Sobel, chief of Wayne State’s division of infectious diseases. The medication was well tolerated in the study.

Unfortunately and as is often the case with BV, "these patients recurred and recurred rapidly after stopping maintenance therapy," said coauthor and ob.gyn. Tina Aguin, also of Wayne State.

Six of nine patients relapsed within 3 months. "The bottom line is we are able to control people with intravaginal high-dose metronidazole maintenance, but we are not curing anyone," she said.

Dr. Aguin and Dr. Sobel said they had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – It’s necessary to use metronidazole in addition to doxycycline and a cephalosporin to cover all the bacteria species associated with pelvic inflammatory disease, according to an analysis of 198 endometrial biopsy isolates from 170 women with the condition.

"The coadministration of a cephalosporin with doxycycline for women with PID provides coverage for all anaerobic pathogens except Prevotella species. The addition of metronidazole is necessary to provide coverage for these anaerobic gram-negative rods," investigators from the University of Pittsburgh concluded.

Twelve percent of the women had Prevotella species in their endometrium that were resistant to both ceftriaxone and doxycycline, but not metronidazole.

The Centers for Disease Control and Prevention currently recommends an injectable cephalosporin and oral doxycycline for outpatient PID, but lets clinicians decide whether to include metronidazole.

"If you are going to cover the spectrum of organisms that are there, you really have to add the metronidazole," said senior investigator Sharon L. Hillier, Ph.D., professor of obstetrics, gynecology, and reproductive sciences in the division of infectious diseases at the university.

But "there’s reticence to prescribe it in addition to doxycycline because of the GI upset and lack of tolerance. The concern is that people might not finish their antimicrobials and get worse. It’s truly a conundrum; we don’t have a good alternative to metronidazole," Dr. Hillier said at the annual meeting of the Infectious Diseases Society of Obstetrics and Gynecology.

Also, "there aren’t longitudinal data yet that show that women with untreated Prevotella have worse outcomes. There haven’t been data suggesting that failure to cover those has long-term infertility sequelae. My own view is that we probably should use metronidazole. The bottom line is that no two antibiotics cover everything," she said.

Biopsies from 65 women – all outpatients 15-40 years old with clinical PID diagnoses – grew out one or more organisms. In all, 17 types or species of bacteria were isolated.

Gardnerella vaginalis, Atopobium vaginae, and Prevotella and Lactobacillus species made up 81% of the isolates.

Ceftriaxone was effective for all of them except the Prevotella, while metronidazole was effective against only the Prevotella. Doxycycline susceptibilities ranged from 47% for A. vaginae to 82% for G. vaginalis.

With the exception of Prevotella, ceftriaxone and doxycycline "are effective against many of the anaerobic and facultative bacteria associated with" PID, the researchers concluded.

aotto@frontlinemedcom.com

Metformin appears to have slowed, or perhaps even halted, the progression of prostate cancer in a retrospective, Canadian study of 3,837 diabetic men.

The study was published in the Journal of Clinical Oncology.

The longer the men were on the drug, the better they did; for each additional 6 months of treatment following diagnosis, prostate cancer mortality dropped 24% (adjusted hazard ratio 0.76). There was a 24% reduction in all-cause mortality in the first 6 months, as well (aHR, 0.76), but the association faded with time; 24-30 months out from diagnosis, metformin was associated with an all-cause mortality reduction of 7% (aHR, 0.93).

Although some of the men used other diabetes drugs such as sulfonylureas, thiazolidinediones, and insulin some of the time, only metformin improved prostate cancer outcomes, regardless of concomitant cancer treatments.

"We cannot conclude" that a nondiabetic population would see similar benefits, but the results "suggest that metformin may ... improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments. We believe an interventional study of the use of metformin to delay progression in prostate cancer is warranted," wrote Dr. David Margel, a uro-oncology fellow at the University of Toronto when the study was conducted, and now a urologist at the Rabin Medical Center in Petah-Tikva, Israel (J. Clin. Oncol. 2013 Aug 5 [doi: 10.1200/JCO.2012.46.7043]).

Dr. Margel and his team are not the first to suggest that the ubiquitous diabetes drug might also be a potent cancer fighter. Metformin is being tested in dozens of trials not only for prostate tumors, but also for breast, brain, lung, uterine, colorectal, pancreatic, skin, blood, and thyroid cancers.

It probably doesn’t stop benign cells from turning cancerous, but may "influence cancer cells indirectly by decreasing insulin levels or directly by influencing cancer cell proliferation and apoptosis," the investigators wrote.

Study data came from health care databases kept by the province of Ontario, including the Ontario Cancer Registry and Ontario Diabetes Database.

The men were a median of 75 years old at diagnosis, and followed for a median of 4.64 years. About a quarter (976) presented with high-grade tumors, and almost 60% (2,167) with high-volume tumors. Thirty-five percent (1,343) died during the study period; prostate cancer was responsible for 7.6% (291) of the deaths.

"Overall, 1,251 (32.6%) and 1,619 (42.2%) were exposed to metformin before and after [prostate cancer] diagnosis, respectively. Patients were exposed to metformin for a median of 19 months before diagnosis and 8.9 months after diagnosis," Dr. Margel and his team noted.

The Ontario Ministry of Health and Long-Term Care funded the project. The authors have no conflicts of interest.

aotto@frontlinemedcom.com

Metformin appears to have slowed, or perhaps even halted, the progression of prostate cancer in a retrospective, Canadian study of 3,837 diabetic men.

The study was published in the Journal of Clinical Oncology.

The longer the men were on the drug, the better they did; for each additional 6 months of treatment following diagnosis, prostate cancer mortality dropped 24% (adjusted hazard ratio 0.76). There was a 24% reduction in all-cause mortality in the first 6 months, as well (aHR, 0.76), but the association faded with time; 24-30 months out from diagnosis, metformin was associated with an all-cause mortality reduction of 7% (aHR, 0.93).

Although some of the men used other diabetes drugs such as sulfonylureas, thiazolidinediones, and insulin some of the time, only metformin improved prostate cancer outcomes, regardless of concomitant cancer treatments.

"We cannot conclude" that a nondiabetic population would see similar benefits, but the results "suggest that metformin may ... improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments. We believe an interventional study of the use of metformin to delay progression in prostate cancer is warranted," wrote Dr. David Margel, a uro-oncology fellow at the University of Toronto when the study was conducted, and now a urologist at the Rabin Medical Center in Petah-Tikva, Israel (J. Clin. Oncol. 2013 Aug 5 [doi: 10.1200/JCO.2012.46.7043]).

Dr. Margel and his team are not the first to suggest that the ubiquitous diabetes drug might also be a potent cancer fighter. Metformin is being tested in dozens of trials not only for prostate tumors, but also for breast, brain, lung, uterine, colorectal, pancreatic, skin, blood, and thyroid cancers.

It probably doesn’t stop benign cells from turning cancerous, but may "influence cancer cells indirectly by decreasing insulin levels or directly by influencing cancer cell proliferation and apoptosis," the investigators wrote.

Study data came from health care databases kept by the province of Ontario, including the Ontario Cancer Registry and Ontario Diabetes Database.

The men were a median of 75 years old at diagnosis, and followed for a median of 4.64 years. About a quarter (976) presented with high-grade tumors, and almost 60% (2,167) with high-volume tumors. Thirty-five percent (1,343) died during the study period; prostate cancer was responsible for 7.6% (291) of the deaths.

"Overall, 1,251 (32.6%) and 1,619 (42.2%) were exposed to metformin before and after [prostate cancer] diagnosis, respectively. Patients were exposed to metformin for a median of 19 months before diagnosis and 8.9 months after diagnosis," Dr. Margel and his team noted.

The Ontario Ministry of Health and Long-Term Care funded the project. The authors have no conflicts of interest.

aotto@frontlinemedcom.com

Metformin appears to have slowed, or perhaps even halted, the progression of prostate cancer in a retrospective, Canadian study of 3,837 diabetic men.

The study was published in the Journal of Clinical Oncology.

The longer the men were on the drug, the better they did; for each additional 6 months of treatment following diagnosis, prostate cancer mortality dropped 24% (adjusted hazard ratio 0.76). There was a 24% reduction in all-cause mortality in the first 6 months, as well (aHR, 0.76), but the association faded with time; 24-30 months out from diagnosis, metformin was associated with an all-cause mortality reduction of 7% (aHR, 0.93).

Although some of the men used other diabetes drugs such as sulfonylureas, thiazolidinediones, and insulin some of the time, only metformin improved prostate cancer outcomes, regardless of concomitant cancer treatments.

"We cannot conclude" that a nondiabetic population would see similar benefits, but the results "suggest that metformin may ... improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments. We believe an interventional study of the use of metformin to delay progression in prostate cancer is warranted," wrote Dr. David Margel, a uro-oncology fellow at the University of Toronto when the study was conducted, and now a urologist at the Rabin Medical Center in Petah-Tikva, Israel (J. Clin. Oncol. 2013 Aug 5 [doi: 10.1200/JCO.2012.46.7043]).

Dr. Margel and his team are not the first to suggest that the ubiquitous diabetes drug might also be a potent cancer fighter. Metformin is being tested in dozens of trials not only for prostate tumors, but also for breast, brain, lung, uterine, colorectal, pancreatic, skin, blood, and thyroid cancers.

It probably doesn’t stop benign cells from turning cancerous, but may "influence cancer cells indirectly by decreasing insulin levels or directly by influencing cancer cell proliferation and apoptosis," the investigators wrote.

Study data came from health care databases kept by the province of Ontario, including the Ontario Cancer Registry and Ontario Diabetes Database.

The men were a median of 75 years old at diagnosis, and followed for a median of 4.64 years. About a quarter (976) presented with high-grade tumors, and almost 60% (2,167) with high-volume tumors. Thirty-five percent (1,343) died during the study period; prostate cancer was responsible for 7.6% (291) of the deaths.

"Overall, 1,251 (32.6%) and 1,619 (42.2%) were exposed to metformin before and after [prostate cancer] diagnosis, respectively. Patients were exposed to metformin for a median of 19 months before diagnosis and 8.9 months after diagnosis," Dr. Margel and his team noted.

The Ontario Ministry of Health and Long-Term Care funded the project. The authors have no conflicts of interest.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Count arthritis among the possible side effects of clopidogrel, according to investigators from the Westchester Medical Center in Valhalla, N.Y.

The number of reported cases – 11 – is vanishingly small compared with the number of people who have used the drug. In 2012 alone, 11.3 million prescriptions were written for the branded product Plavix in the United States, according to IMS Health, a health care information company.

Still, it’s something to keep in mind if a patient suddenly develops stiff, swollen joints shortly after starting the drug, exactly what happened to a 64-year-old man at the medical center following a 300-mg loading dose and a few days of 75-mg maintenance therapy after stent placement.

"He had been on the maintenance dose for 3 days when he first started to have a fever, and then he started to have joint symptoms" about 2 weeks after the procedure, said Dr. Sahil Agrawal, an internal medicine resident and lead investigator. The fever persisted, and did not respond to antibiotics.

The man presented with a stiff neck, painful right shoulder, and markedly limited range of motion in both joints; the next day he developed painful swelling, redness, and a restricted range of motion in both hands and wrists. His erythrocyte sedimentation rate and C-reactive protein levels were both elevated, but findings from uric acid concentration and other tests were normal. Radiographs of the affected joints showed only degenerative changes; a few white cells were aspirated from his shoulder joint. He was negative for Lyme disease, brucellosis, and familial Mediterranean fever.

"We did an extensive differential diagnosis and ruled out everything under the sun. At the same time, we learned that he had [similar] symptoms with" a single loading dose of Plavix a year earlier, "so we went back into the literature. Once we had an idea that this was possible, we stopped his clopidogrel and switched him to prasugrel. Within the next few days, his symptoms went away and have not come back," Dr. Agrawal said at the 18th World Congress on Heart Disease.

The timing of the man’s symptoms and their quick resolution when the drug was stopped "strongly suggest clopidogrel-associated arthritis. [Previous authors have] advised careful use of clopidogrel in patients with a history of arthritis. We recommend considering clopidogrel as a cause of acute arthritis," and avoiding using it again "in patients with a prior unexplained episode of arthritis temporally related to clopidogrel therapy," Dr. Agrawal and his colleagues concluded in their recently published case report and literature review (J. Investig. Med. 2013 Aug. 5 [doi:10.1177/2324709613500239]).

All but 1 of the previous 10 reported cases were in men. Joint symptoms started after 2-3 weeks of maintenance therapy, except in one case when they started after 3 days. Both small and large joints were affected, usually more than one. Synovitis was the hallmark exam finding.

Erythrocyte sedimentation rate and C-reactive protein levels were elevated in all cases; fever, itching, and maculopapular rashes were also common. The pattern "suggests a possible immunologic basis for these symptoms," the investigators noted.

In every case, the symptoms went away shortly after clopidogrel was stopped.

Dr. Agrawal and his colleagues reported having no relevant financial disclosures.

motto@frontlinemedcom.com

VANCOUVER, B.C. – Count arthritis among the possible side effects of clopidogrel, according to investigators from the Westchester Medical Center in Valhalla, N.Y.

The number of reported cases – 11 – is vanishingly small compared with the number of people who have used the drug. In 2012 alone, 11.3 million prescriptions were written for the branded product Plavix in the United States, according to IMS Health, a health care information company.

Still, it’s something to keep in mind if a patient suddenly develops stiff, swollen joints shortly after starting the drug, exactly what happened to a 64-year-old man at the medical center following a 300-mg loading dose and a few days of 75-mg maintenance therapy after stent placement.

"He had been on the maintenance dose for 3 days when he first started to have a fever, and then he started to have joint symptoms" about 2 weeks after the procedure, said Dr. Sahil Agrawal, an internal medicine resident and lead investigator. The fever persisted, and did not respond to antibiotics.

The man presented with a stiff neck, painful right shoulder, and markedly limited range of motion in both joints; the next day he developed painful swelling, redness, and a restricted range of motion in both hands and wrists. His erythrocyte sedimentation rate and C-reactive protein levels were both elevated, but findings from uric acid concentration and other tests were normal. Radiographs of the affected joints showed only degenerative changes; a few white cells were aspirated from his shoulder joint. He was negative for Lyme disease, brucellosis, and familial Mediterranean fever.

"We did an extensive differential diagnosis and ruled out everything under the sun. At the same time, we learned that he had [similar] symptoms with" a single loading dose of Plavix a year earlier, "so we went back into the literature. Once we had an idea that this was possible, we stopped his clopidogrel and switched him to prasugrel. Within the next few days, his symptoms went away and have not come back," Dr. Agrawal said at the 18th World Congress on Heart Disease.

The timing of the man’s symptoms and their quick resolution when the drug was stopped "strongly suggest clopidogrel-associated arthritis. [Previous authors have] advised careful use of clopidogrel in patients with a history of arthritis. We recommend considering clopidogrel as a cause of acute arthritis," and avoiding using it again "in patients with a prior unexplained episode of arthritis temporally related to clopidogrel therapy," Dr. Agrawal and his colleagues concluded in their recently published case report and literature review (J. Investig. Med. 2013 Aug. 5 [doi:10.1177/2324709613500239]).

All but 1 of the previous 10 reported cases were in men. Joint symptoms started after 2-3 weeks of maintenance therapy, except in one case when they started after 3 days. Both small and large joints were affected, usually more than one. Synovitis was the hallmark exam finding.

Erythrocyte sedimentation rate and C-reactive protein levels were elevated in all cases; fever, itching, and maculopapular rashes were also common. The pattern "suggests a possible immunologic basis for these symptoms," the investigators noted.

In every case, the symptoms went away shortly after clopidogrel was stopped.

Dr. Agrawal and his colleagues reported having no relevant financial disclosures.

motto@frontlinemedcom.com

VANCOUVER, B.C. – Count arthritis among the possible side effects of clopidogrel, according to investigators from the Westchester Medical Center in Valhalla, N.Y.

The number of reported cases – 11 – is vanishingly small compared with the number of people who have used the drug. In 2012 alone, 11.3 million prescriptions were written for the branded product Plavix in the United States, according to IMS Health, a health care information company.

Still, it’s something to keep in mind if a patient suddenly develops stiff, swollen joints shortly after starting the drug, exactly what happened to a 64-year-old man at the medical center following a 300-mg loading dose and a few days of 75-mg maintenance therapy after stent placement.

"He had been on the maintenance dose for 3 days when he first started to have a fever, and then he started to have joint symptoms" about 2 weeks after the procedure, said Dr. Sahil Agrawal, an internal medicine resident and lead investigator. The fever persisted, and did not respond to antibiotics.

The man presented with a stiff neck, painful right shoulder, and markedly limited range of motion in both joints; the next day he developed painful swelling, redness, and a restricted range of motion in both hands and wrists. His erythrocyte sedimentation rate and C-reactive protein levels were both elevated, but findings from uric acid concentration and other tests were normal. Radiographs of the affected joints showed only degenerative changes; a few white cells were aspirated from his shoulder joint. He was negative for Lyme disease, brucellosis, and familial Mediterranean fever.

"We did an extensive differential diagnosis and ruled out everything under the sun. At the same time, we learned that he had [similar] symptoms with" a single loading dose of Plavix a year earlier, "so we went back into the literature. Once we had an idea that this was possible, we stopped his clopidogrel and switched him to prasugrel. Within the next few days, his symptoms went away and have not come back," Dr. Agrawal said at the 18th World Congress on Heart Disease.

The timing of the man’s symptoms and their quick resolution when the drug was stopped "strongly suggest clopidogrel-associated arthritis. [Previous authors have] advised careful use of clopidogrel in patients with a history of arthritis. We recommend considering clopidogrel as a cause of acute arthritis," and avoiding using it again "in patients with a prior unexplained episode of arthritis temporally related to clopidogrel therapy," Dr. Agrawal and his colleagues concluded in their recently published case report and literature review (J. Investig. Med. 2013 Aug. 5 [doi:10.1177/2324709613500239]).

All but 1 of the previous 10 reported cases were in men. Joint symptoms started after 2-3 weeks of maintenance therapy, except in one case when they started after 3 days. Both small and large joints were affected, usually more than one. Synovitis was the hallmark exam finding.

Erythrocyte sedimentation rate and C-reactive protein levels were elevated in all cases; fever, itching, and maculopapular rashes were also common. The pattern "suggests a possible immunologic basis for these symptoms," the investigators noted.

In every case, the symptoms went away shortly after clopidogrel was stopped.

Dr. Agrawal and his colleagues reported having no relevant financial disclosures.

motto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – A score of 6 or greater on a sepsis risk scale specifically for pregnant women had an adjusted odds ratio of 109 for ICU admission, with a 95% confidence interval of 18-661, according to its developers at Brown University in Providence, R.I.

Dubbed the Sepsis in Obstetrics Score (SOS), the scale is based on the Rapid Emergency Medicine Score and the SIRS/Sepsis criteria, but is adjusted to reflect the slightly higher heart rates, lower blood pressures, and elevated white counts associated with pregnancy. Scores range from 0-28, with 0 being normal.

The team applied the scoring system retrospectively to 850 pregnant or recently postpartum women who had gotten blood cultures or influenza swabs in the ED; both were used as surrogate markers for septic presentations.

Forty-eight women had scores of at least 6, and eight were admitted to the ICU. There was one ICU admission among the 802 women with scores less than 6.

In addition to the high odds ratio, which was adjusted for age, race, and body mass index, a score of at least 6 had a sensitivity of 88.9%, a specificity of 95.2%, a negative predictive value of 99.9%, and a positive predictive value of 16.7% for ICU admission within 48 hours of presentation.

"In this population in general, there is a low overall rate of serious morbidity and mortality, resulting in our low positive predictive value; it is, however, significantly higher than other disease severity scoring systems studied in this population," said lead investigator Dr. Catherine Albright, an ob.gyn. resident at Brown.

A score of at least 6 also was independently associated with telemetry unit admission, length of hospital stay, fetal tachycardia, and positive blood cultures; the latter were found in 30.8% of women who met the cutoff, but only 8.5% of women who did not. There was no significant difference in the percentage of women with positive flu swabs, about 14% in each group.

"None of the current disease severity scoring systems included pregnant women in their initial study populations. They uniformly overestimate morbidity and mortality in obstetric populations," whereas SOS "can reliably identify patients" who require ICU treatment, Dr. Albright said. The next step is prospective validation, she added.

However, during the question and answer period, an audience member pointed out that the researchers "used your own cohort to develop the cutoff, and then applied that cutoff to the same cohort, and got a high odds ratio; that’s really not surprising. I think your follow-up of applying this to a different cohort [will be] really important."

"Absolutely," Dr. Albright responded.

The score includes temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, white blood cell count, percentage of immature neutrophils, and lactic acid concentration. With adjustment for pregnancy, a heart rate up to 120 bpm, a WBC count of about 6-17,000 cells/mcL, and a systolic blood pressure down to 90 mm Hg are considered to be in the normal range.

Among higher-scoring women, the most common diagnoses at presentation were pyelonephritis and endometritis. Those with scores below six were most commonly diagnosed with influenzalike illness, Dr. Albright reported at the Infectious Diseases Society for Obstetrics and Gynecology annual meeting

There were no significant differences between the two groups in the presence of hypertension, diabetes, HIV, and other comorbidities. The only significant demographic difference was age, with higher-scoring women a mean of 24 years old, vs. 26.3 in the lower-scoring group, probably a clinically irrelevant finding, she said.

Known or suspected ectopic pregnancies and multiple gestations were among the exclusion criteria.

Dr. Albright said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – A score of 6 or greater on a sepsis risk scale specifically for pregnant women had an adjusted odds ratio of 109 for ICU admission, with a 95% confidence interval of 18-661, according to its developers at Brown University in Providence, R.I.

Dubbed the Sepsis in Obstetrics Score (SOS), the scale is based on the Rapid Emergency Medicine Score and the SIRS/Sepsis criteria, but is adjusted to reflect the slightly higher heart rates, lower blood pressures, and elevated white counts associated with pregnancy. Scores range from 0-28, with 0 being normal.

The team applied the scoring system retrospectively to 850 pregnant or recently postpartum women who had gotten blood cultures or influenza swabs in the ED; both were used as surrogate markers for septic presentations.

Forty-eight women had scores of at least 6, and eight were admitted to the ICU. There was one ICU admission among the 802 women with scores less than 6.

In addition to the high odds ratio, which was adjusted for age, race, and body mass index, a score of at least 6 had a sensitivity of 88.9%, a specificity of 95.2%, a negative predictive value of 99.9%, and a positive predictive value of 16.7% for ICU admission within 48 hours of presentation.

"In this population in general, there is a low overall rate of serious morbidity and mortality, resulting in our low positive predictive value; it is, however, significantly higher than other disease severity scoring systems studied in this population," said lead investigator Dr. Catherine Albright, an ob.gyn. resident at Brown.

A score of at least 6 also was independently associated with telemetry unit admission, length of hospital stay, fetal tachycardia, and positive blood cultures; the latter were found in 30.8% of women who met the cutoff, but only 8.5% of women who did not. There was no significant difference in the percentage of women with positive flu swabs, about 14% in each group.

"None of the current disease severity scoring systems included pregnant women in their initial study populations. They uniformly overestimate morbidity and mortality in obstetric populations," whereas SOS "can reliably identify patients" who require ICU treatment, Dr. Albright said. The next step is prospective validation, she added.

However, during the question and answer period, an audience member pointed out that the researchers "used your own cohort to develop the cutoff, and then applied that cutoff to the same cohort, and got a high odds ratio; that’s really not surprising. I think your follow-up of applying this to a different cohort [will be] really important."

"Absolutely," Dr. Albright responded.

The score includes temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, white blood cell count, percentage of immature neutrophils, and lactic acid concentration. With adjustment for pregnancy, a heart rate up to 120 bpm, a WBC count of about 6-17,000 cells/mcL, and a systolic blood pressure down to 90 mm Hg are considered to be in the normal range.

Among higher-scoring women, the most common diagnoses at presentation were pyelonephritis and endometritis. Those with scores below six were most commonly diagnosed with influenzalike illness, Dr. Albright reported at the Infectious Diseases Society for Obstetrics and Gynecology annual meeting

There were no significant differences between the two groups in the presence of hypertension, diabetes, HIV, and other comorbidities. The only significant demographic difference was age, with higher-scoring women a mean of 24 years old, vs. 26.3 in the lower-scoring group, probably a clinically irrelevant finding, she said.

Known or suspected ectopic pregnancies and multiple gestations were among the exclusion criteria.

Dr. Albright said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

BERNALILLO, N.M. – A score of 6 or greater on a sepsis risk scale specifically for pregnant women had an adjusted odds ratio of 109 for ICU admission, with a 95% confidence interval of 18-661, according to its developers at Brown University in Providence, R.I.

Dubbed the Sepsis in Obstetrics Score (SOS), the scale is based on the Rapid Emergency Medicine Score and the SIRS/Sepsis criteria, but is adjusted to reflect the slightly higher heart rates, lower blood pressures, and elevated white counts associated with pregnancy. Scores range from 0-28, with 0 being normal.

The team applied the scoring system retrospectively to 850 pregnant or recently postpartum women who had gotten blood cultures or influenza swabs in the ED; both were used as surrogate markers for septic presentations.

Forty-eight women had scores of at least 6, and eight were admitted to the ICU. There was one ICU admission among the 802 women with scores less than 6.

In addition to the high odds ratio, which was adjusted for age, race, and body mass index, a score of at least 6 had a sensitivity of 88.9%, a specificity of 95.2%, a negative predictive value of 99.9%, and a positive predictive value of 16.7% for ICU admission within 48 hours of presentation.

"In this population in general, there is a low overall rate of serious morbidity and mortality, resulting in our low positive predictive value; it is, however, significantly higher than other disease severity scoring systems studied in this population," said lead investigator Dr. Catherine Albright, an ob.gyn. resident at Brown.

A score of at least 6 also was independently associated with telemetry unit admission, length of hospital stay, fetal tachycardia, and positive blood cultures; the latter were found in 30.8% of women who met the cutoff, but only 8.5% of women who did not. There was no significant difference in the percentage of women with positive flu swabs, about 14% in each group.

"None of the current disease severity scoring systems included pregnant women in their initial study populations. They uniformly overestimate morbidity and mortality in obstetric populations," whereas SOS "can reliably identify patients" who require ICU treatment, Dr. Albright said. The next step is prospective validation, she added.

However, during the question and answer period, an audience member pointed out that the researchers "used your own cohort to develop the cutoff, and then applied that cutoff to the same cohort, and got a high odds ratio; that’s really not surprising. I think your follow-up of applying this to a different cohort [will be] really important."

"Absolutely," Dr. Albright responded.

The score includes temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, white blood cell count, percentage of immature neutrophils, and lactic acid concentration. With adjustment for pregnancy, a heart rate up to 120 bpm, a WBC count of about 6-17,000 cells/mcL, and a systolic blood pressure down to 90 mm Hg are considered to be in the normal range.

Among higher-scoring women, the most common diagnoses at presentation were pyelonephritis and endometritis. Those with scores below six were most commonly diagnosed with influenzalike illness, Dr. Albright reported at the Infectious Diseases Society for Obstetrics and Gynecology annual meeting

There were no significant differences between the two groups in the presence of hypertension, diabetes, HIV, and other comorbidities. The only significant demographic difference was age, with higher-scoring women a mean of 24 years old, vs. 26.3 in the lower-scoring group, probably a clinically irrelevant finding, she said.

Known or suspected ectopic pregnancies and multiple gestations were among the exclusion criteria.

Dr. Albright said she had no relevant financial disclosures.

aotto@frontlinemedcom.com

Among patients with community-associated Clostridium difficile infection, more than a third had not used antibiotics in the 12 weeks before diagnosis and more than half reported limited or no health care contact over the same period.

To assess possible sources of infection, Dr. Amit S. Chitnis and his colleagues at the Centers for Disease Control and Prevention reviewed the medical records of, and interviewed, 984 patients with new-onset community-associated C. difficile infection (CDI).

The patients’ median age was 51 years and median Charlson comorbidity index 0. Almost 90% were white; two-thirds were women; 41% had preceding outpatient care such as surgery or dialysis.

Investigators found that 400 patients (41%) reported low-level health care exposure, such as a visit to a physician or dentist, while 177 (18%) reported no exposure (JAMA Intern. Med. 2013;173:1359-67).

Sixty-four percent (631) reported antibiotic use within 12 weeks of diagnosis, while 28% (273) reported using a PPI, and 9% (90) reported using an H₂-receptor antagonist. Among 177 patients with no health care contact, 44% had used antibiotics, 24% used a PPI, and 12% had used H₂-receptor antagonists.

Patients with no, or limited, health care contact were significantly more likely to live with an active CDI case or have contact with infants under a year old, who can be asymptomatic CDI carriers. There were no associations between CDI and animal exposure. "Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings," the investigators concluded. They suggested evaluating CDI transmission in household settings and reduction of PPI use.

The CDC funded the work. The authors reported no conflicts of interest.

aotto@frontlinemedcom.com

Among patients with community-associated Clostridium difficile infection, more than a third had not used antibiotics in the 12 weeks before diagnosis and more than half reported limited or no health care contact over the same period.

To assess possible sources of infection, Dr. Amit S. Chitnis and his colleagues at the Centers for Disease Control and Prevention reviewed the medical records of, and interviewed, 984 patients with new-onset community-associated C. difficile infection (CDI).

The patients’ median age was 51 years and median Charlson comorbidity index 0. Almost 90% were white; two-thirds were women; 41% had preceding outpatient care such as surgery or dialysis.

Investigators found that 400 patients (41%) reported low-level health care exposure, such as a visit to a physician or dentist, while 177 (18%) reported no exposure (JAMA Intern. Med. 2013;173:1359-67).

Sixty-four percent (631) reported antibiotic use within 12 weeks of diagnosis, while 28% (273) reported using a PPI, and 9% (90) reported using an H₂-receptor antagonist. Among 177 patients with no health care contact, 44% had used antibiotics, 24% used a PPI, and 12% had used H₂-receptor antagonists.

Patients with no, or limited, health care contact were significantly more likely to live with an active CDI case or have contact with infants under a year old, who can be asymptomatic CDI carriers. There were no associations between CDI and animal exposure. "Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings," the investigators concluded. They suggested evaluating CDI transmission in household settings and reduction of PPI use.

The CDC funded the work. The authors reported no conflicts of interest.

aotto@frontlinemedcom.com

Among patients with community-associated Clostridium difficile infection, more than a third had not used antibiotics in the 12 weeks before diagnosis and more than half reported limited or no health care contact over the same period.

To assess possible sources of infection, Dr. Amit S. Chitnis and his colleagues at the Centers for Disease Control and Prevention reviewed the medical records of, and interviewed, 984 patients with new-onset community-associated C. difficile infection (CDI).

The patients’ median age was 51 years and median Charlson comorbidity index 0. Almost 90% were white; two-thirds were women; 41% had preceding outpatient care such as surgery or dialysis.

Investigators found that 400 patients (41%) reported low-level health care exposure, such as a visit to a physician or dentist, while 177 (18%) reported no exposure (JAMA Intern. Med. 2013;173:1359-67).

Sixty-four percent (631) reported antibiotic use within 12 weeks of diagnosis, while 28% (273) reported using a PPI, and 9% (90) reported using an H₂-receptor antagonist. Among 177 patients with no health care contact, 44% had used antibiotics, 24% used a PPI, and 12% had used H₂-receptor antagonists.

Patients with no, or limited, health care contact were significantly more likely to live with an active CDI case or have contact with infants under a year old, who can be asymptomatic CDI carriers. There were no associations between CDI and animal exposure. "Prevention of community-associated CDI should primarily focus on reducing inappropriate antibiotic use and better infection control practices in outpatient settings," the investigators concluded. They suggested evaluating CDI transmission in household settings and reduction of PPI use.

The CDC funded the work. The authors reported no conflicts of interest.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Among patients undergoing percutaneous coronary interventions, bivalirudin was associated with significantly fewer bleeding complications than eptifibatide, but bleeding complications were more severe with bivalirudin, according to a retrospective case-cohort study from Mt. Auburn Hospital in Cambridge, Mass.

Investigators compared bleeding complications among 660 angioplasty patients who received bivalirudin (Angiomax) with 345 who received eptifibatide (Integrilin) instead. MIs were the most common indication for intervention.

Just 31 (3%) of those patients had a bleeding episode; 1 patient was excluded for receiving both medications. Of the remaining bleeding cases, 10 were in the bivalirudin group, and 20 were in the eptifibatide group, a significant difference.

However, 7 of those 10 bivalirudin bleeding cases were severe according to GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) criteria, meaning patients had either intracranial hemorrhages or bleeding that caused hemodynamic compromise and required intervention. One patient had a retroperitoneal bleed that required 10 transfusions and surgical hematoma decompression. Among eptifibatide patients, 7 cases (35%) were severe.

There were three moderate bleeding cases – bleeding that required blood transfusions but did not result in hemodynamic compromise – among bivalirudin patients, and nine in the eptifibatide group, which also had four mild bleeds. For bivalirudin bleeding cases, the average length of hospital stay was 9.6 days; for eptifibatide cases, 8.7 days. Urgent PCI cases were associated with more bleeding complications.

All of the patients were on aspirin, with most also given thienopyridines. About 20% in each group were on warfarin. About 90% of patients on eptifibatide, an antiplatelet drug, were on concomitant heparin, compared with 20% on bivalirudin, itself an anticoagulant.

Bivalirudin is generally thought to cause less bleeding, but "we never looked at the severity of those [bleeds]. Although bivalirudin caused less bleeding, those episodes tended to be much more serious," something that was "unexpected," said lead investigator Dr. Smita Kohli, a cardiology research fellow now at Henry Ford Hospital in Detroit.

Age may have played a role. Eptifibatide bleeders were aged 66 years on average, but bivalirudin bleeders were aged 76 years. Because they were older, maybe they had a greater risk of severe bleeding, Dr. Kohli suggested. Another potential factor – kidney function – did not seem to play a role. Patients in both groups "had similar baseline kidney function," with a mean creatinine level of 1.0 mg/dL, Dr. Kohli said at the 18th World Congress on Heart Disease.

The numbers in the study are small, and "we haven’t really identified what caused those cases to be severe," she said. For now, the findings are more hypothesis generating, not a guide to practice, she added.

Dr. Kohli said she has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Among patients undergoing percutaneous coronary interventions, bivalirudin was associated with significantly fewer bleeding complications than eptifibatide, but bleeding complications were more severe with bivalirudin, according to a retrospective case-cohort study from Mt. Auburn Hospital in Cambridge, Mass.

Investigators compared bleeding complications among 660 angioplasty patients who received bivalirudin (Angiomax) with 345 who received eptifibatide (Integrilin) instead. MIs were the most common indication for intervention.

Just 31 (3%) of those patients had a bleeding episode; 1 patient was excluded for receiving both medications. Of the remaining bleeding cases, 10 were in the bivalirudin group, and 20 were in the eptifibatide group, a significant difference.

However, 7 of those 10 bivalirudin bleeding cases were severe according to GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) criteria, meaning patients had either intracranial hemorrhages or bleeding that caused hemodynamic compromise and required intervention. One patient had a retroperitoneal bleed that required 10 transfusions and surgical hematoma decompression. Among eptifibatide patients, 7 cases (35%) were severe.

There were three moderate bleeding cases – bleeding that required blood transfusions but did not result in hemodynamic compromise – among bivalirudin patients, and nine in the eptifibatide group, which also had four mild bleeds. For bivalirudin bleeding cases, the average length of hospital stay was 9.6 days; for eptifibatide cases, 8.7 days. Urgent PCI cases were associated with more bleeding complications.

All of the patients were on aspirin, with most also given thienopyridines. About 20% in each group were on warfarin. About 90% of patients on eptifibatide, an antiplatelet drug, were on concomitant heparin, compared with 20% on bivalirudin, itself an anticoagulant.

Bivalirudin is generally thought to cause less bleeding, but "we never looked at the severity of those [bleeds]. Although bivalirudin caused less bleeding, those episodes tended to be much more serious," something that was "unexpected," said lead investigator Dr. Smita Kohli, a cardiology research fellow now at Henry Ford Hospital in Detroit.

Age may have played a role. Eptifibatide bleeders were aged 66 years on average, but bivalirudin bleeders were aged 76 years. Because they were older, maybe they had a greater risk of severe bleeding, Dr. Kohli suggested. Another potential factor – kidney function – did not seem to play a role. Patients in both groups "had similar baseline kidney function," with a mean creatinine level of 1.0 mg/dL, Dr. Kohli said at the 18th World Congress on Heart Disease.

The numbers in the study are small, and "we haven’t really identified what caused those cases to be severe," she said. For now, the findings are more hypothesis generating, not a guide to practice, she added.

Dr. Kohli said she has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Among patients undergoing percutaneous coronary interventions, bivalirudin was associated with significantly fewer bleeding complications than eptifibatide, but bleeding complications were more severe with bivalirudin, according to a retrospective case-cohort study from Mt. Auburn Hospital in Cambridge, Mass.

Investigators compared bleeding complications among 660 angioplasty patients who received bivalirudin (Angiomax) with 345 who received eptifibatide (Integrilin) instead. MIs were the most common indication for intervention.

Just 31 (3%) of those patients had a bleeding episode; 1 patient was excluded for receiving both medications. Of the remaining bleeding cases, 10 were in the bivalirudin group, and 20 were in the eptifibatide group, a significant difference.

However, 7 of those 10 bivalirudin bleeding cases were severe according to GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) criteria, meaning patients had either intracranial hemorrhages or bleeding that caused hemodynamic compromise and required intervention. One patient had a retroperitoneal bleed that required 10 transfusions and surgical hematoma decompression. Among eptifibatide patients, 7 cases (35%) were severe.

There were three moderate bleeding cases – bleeding that required blood transfusions but did not result in hemodynamic compromise – among bivalirudin patients, and nine in the eptifibatide group, which also had four mild bleeds. For bivalirudin bleeding cases, the average length of hospital stay was 9.6 days; for eptifibatide cases, 8.7 days. Urgent PCI cases were associated with more bleeding complications.

All of the patients were on aspirin, with most also given thienopyridines. About 20% in each group were on warfarin. About 90% of patients on eptifibatide, an antiplatelet drug, were on concomitant heparin, compared with 20% on bivalirudin, itself an anticoagulant.

Bivalirudin is generally thought to cause less bleeding, but "we never looked at the severity of those [bleeds]. Although bivalirudin caused less bleeding, those episodes tended to be much more serious," something that was "unexpected," said lead investigator Dr. Smita Kohli, a cardiology research fellow now at Henry Ford Hospital in Detroit.

Age may have played a role. Eptifibatide bleeders were aged 66 years on average, but bivalirudin bleeders were aged 76 years. Because they were older, maybe they had a greater risk of severe bleeding, Dr. Kohli suggested. Another potential factor – kidney function – did not seem to play a role. Patients in both groups "had similar baseline kidney function," with a mean creatinine level of 1.0 mg/dL, Dr. Kohli said at the 18th World Congress on Heart Disease.

The numbers in the study are small, and "we haven’t really identified what caused those cases to be severe," she said. For now, the findings are more hypothesis generating, not a guide to practice, she added.

Dr. Kohli said she has no disclosures.

aotto@frontlinemedcom.com