Jennie Smith

Tocilizumab (Actemra) is approved for the treatment of young people with active systemic juvenile idiopathic arthritis, a rare and severe form of inflammatory arthritis, according to a statement from the Food and Drug Administration.

The interleukin-6 receptor blocker was approved in January of 2010 for adults with moderate to severe rheumatoid arthritis that does not respond to other therapies.

The new juvenile indication, announced April 15, is for children, aged 2 years and older, with active systemic juvenile idiopathic arthritis (SJIA), or Still’s disease, a potentially life-threatening disorder that causes swelling and inflammation of the lymph nodes, liver, and spleen, among other effects.

Juvenile idiopathic arthritis is estimated to affect 1-2 children per 1,000, and SJIA, the most severe form of JIA, is seen in about 10% of those cases, according to the FDA. Tocilizumab is the first medication specifically approved by the agency for this patient group. It can be used as monotherapy or in combination with methotrexate.

The agency based the approval on results from a randomized, placebo-controlled trial involving 112 patients, aged 2-17 years, with active SJIA for at least 6 months. The participants either could not tolerate or did not respond well to their current therapies (nonsteroidal disease-modifying drugs and/or systemic corticosteroids). They were randomly assigned to receive tocilizumab intravenous infusions (8 mg/kg or 12 mg/kg depending on weight) or placebo every 2 weeks.

After 12 weeks, 85% of children in the treatment group responded to treatment compared with 24% of children in the control group. Treatment response was defined as at least a 30% improvement according to the American College of Rheumatology’s JIA efficacy variables, and the absence of fever in the preceding 7 days.

The medication carries an FDA boxed warning for serious infections. Patients treated with tocilizumab who develop serious infections should discontinue treatment until the infection is controlled.

Changes in certain laboratory test results such as liver tests, blood counts, and cholesterol are not uncommon with tocilizumab and should be monitored with regular blood tests, according to an FDA statement.

Three cases of macrophage activation syndrome occurred among the patients receiving tocilizumab.

The most common side effects included upper respiratory tract infection, headache, sore throat, and diarrhea.

Tocilizumab (Actemra) is approved for the treatment of young people with active systemic juvenile idiopathic arthritis, a rare and severe form of inflammatory arthritis, according to a statement from the Food and Drug Administration.

The interleukin-6 receptor blocker was approved in January of 2010 for adults with moderate to severe rheumatoid arthritis that does not respond to other therapies.

The new juvenile indication, announced April 15, is for children, aged 2 years and older, with active systemic juvenile idiopathic arthritis (SJIA), or Still’s disease, a potentially life-threatening disorder that causes swelling and inflammation of the lymph nodes, liver, and spleen, among other effects.

Juvenile idiopathic arthritis is estimated to affect 1-2 children per 1,000, and SJIA, the most severe form of JIA, is seen in about 10% of those cases, according to the FDA. Tocilizumab is the first medication specifically approved by the agency for this patient group. It can be used as monotherapy or in combination with methotrexate.

The agency based the approval on results from a randomized, placebo-controlled trial involving 112 patients, aged 2-17 years, with active SJIA for at least 6 months. The participants either could not tolerate or did not respond well to their current therapies (nonsteroidal disease-modifying drugs and/or systemic corticosteroids). They were randomly assigned to receive tocilizumab intravenous infusions (8 mg/kg or 12 mg/kg depending on weight) or placebo every 2 weeks.

After 12 weeks, 85% of children in the treatment group responded to treatment compared with 24% of children in the control group. Treatment response was defined as at least a 30% improvement according to the American College of Rheumatology’s JIA efficacy variables, and the absence of fever in the preceding 7 days.

The medication carries an FDA boxed warning for serious infections. Patients treated with tocilizumab who develop serious infections should discontinue treatment until the infection is controlled.

Changes in certain laboratory test results such as liver tests, blood counts, and cholesterol are not uncommon with tocilizumab and should be monitored with regular blood tests, according to an FDA statement.

Three cases of macrophage activation syndrome occurred among the patients receiving tocilizumab.

The most common side effects included upper respiratory tract infection, headache, sore throat, and diarrhea.

Tocilizumab (Actemra) is approved for the treatment of young people with active systemic juvenile idiopathic arthritis, a rare and severe form of inflammatory arthritis, according to a statement from the Food and Drug Administration.

The interleukin-6 receptor blocker was approved in January of 2010 for adults with moderate to severe rheumatoid arthritis that does not respond to other therapies.

The new juvenile indication, announced April 15, is for children, aged 2 years and older, with active systemic juvenile idiopathic arthritis (SJIA), or Still’s disease, a potentially life-threatening disorder that causes swelling and inflammation of the lymph nodes, liver, and spleen, among other effects.

Juvenile idiopathic arthritis is estimated to affect 1-2 children per 1,000, and SJIA, the most severe form of JIA, is seen in about 10% of those cases, according to the FDA. Tocilizumab is the first medication specifically approved by the agency for this patient group. It can be used as monotherapy or in combination with methotrexate.

The agency based the approval on results from a randomized, placebo-controlled trial involving 112 patients, aged 2-17 years, with active SJIA for at least 6 months. The participants either could not tolerate or did not respond well to their current therapies (nonsteroidal disease-modifying drugs and/or systemic corticosteroids). They were randomly assigned to receive tocilizumab intravenous infusions (8 mg/kg or 12 mg/kg depending on weight) or placebo every 2 weeks.

After 12 weeks, 85% of children in the treatment group responded to treatment compared with 24% of children in the control group. Treatment response was defined as at least a 30% improvement according to the American College of Rheumatology’s JIA efficacy variables, and the absence of fever in the preceding 7 days.

The medication carries an FDA boxed warning for serious infections. Patients treated with tocilizumab who develop serious infections should discontinue treatment until the infection is controlled.

Changes in certain laboratory test results such as liver tests, blood counts, and cholesterol are not uncommon with tocilizumab and should be monitored with regular blood tests, according to an FDA statement.

Three cases of macrophage activation syndrome occurred among the patients receiving tocilizumab.

The most common side effects included upper respiratory tract infection, headache, sore throat, and diarrhea.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

A probiotic medication has been shown to reduce the risk of recurrent urinary tract infections by nearly half – making it comparable to a prophylactic course of antibiotics, the current standard treatment for recurrent urinary tract infections.

Concerns about increasing resistance to commonly used antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones has led to a search for alternative means to prevent urinary tract infections (UTIs), with recent investigations focusing on hydrogen peroxide-producing strains of lactobacilli.

These lactobacilli comprise the dominant vaginal flora, competing with and regulating other urogenital microbes, including the harmful Escherichia coli. Women with recurrent UTIs have been shown to typically have depletion of vaginal lactobacilli at the time of their E. coli infections (J. Infect. Dis. 1998;178:446-50).

The new findings, from a randomized, placebo-controlled trial of a vaginal suppository containing Lactobacillus crispatus in 100 young women, were published online April 15 in Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52:1212-17).

For their research, Dr. Ann E. Stapleton of the University of Washington in Seattle, and her colleagues, recruited women with current cystitis and histories of recurrent UTI to be randomized to Lactin-V (Osel Inc., Mountain View, Calif.), a product containing L. crispatus, or placebo. The women (median age 21, median number of UTIs before study 4.5) applied either Lactin-V or placebo daily for 5 days, then once weekly for 10 weeks. Participants were seen in scheduled follow-up visits at 1 week (visit 3) and 10 weeks (visit 4) after beginning Lactin-V or placebo and for symptomatic UTIs. Investigators collected urine samples for culture and vaginal swabs to assess the level of colonization of L. crispatus. Of the 50 women randomized in each group, 48 were entered into analysis.

Recurrent culture-confirmed UTI occurred in 7 of 48 women (15%) receiving Lactin-V, compared with 13 of 48 women (27%) receiving placebo (RR 0.5; 95% confidence interval, 0.2-1.2).

The investigators named as one of the strengths of the study the quantitative molecular method used to assess vaginal flora following UTI, which afforded them a more precise picture of changes in the balance of vaginal microbiota than seen in previous trials.

The investigators also noted that high-level vaginal colonization with L. crispatus throughout follow-up was associated with a significant reduction in recurrent UTI only for women using the suppositories. In their analysis, Dr. Stapleton and colleagues called this finding "striking" and hypothesized that the use of Lactin-V "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus," and that the L. crispatus isolate used in the intervention offered "unique properties for protection" over the natural recolonization process.

The investigators did not compare Lactin-V to prophylactic antibiotics in their study. However, they noted that a meta-analysis of 10 randomized controlled trials evaluating continuous antimicrobial prophylaxis (Clin. Evid. [Online] 2008 Jul 17;2008. pii:0801) found rates of rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients, "with a [relative risk] of rUTI that is very comparable to our findings (RR, 0.21; 95% CI, 0.13-0.33)."

Dr. Stapleton and colleagues concluded that "[t]his antimicrobial-sparing, well-tolerated intervention compares favorably with historical data regarding antimicrobial prophylaxis, the current standard of care for the prevention of rUTI."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Research in Women’s Health, National Institutes of Health; Dr. Stapleton and her coauthors said they had no relevant financial disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Testosterone replacement therapy is associated with lowered mortality in men with type 2 diabetes and low testosterone levels, according to U.K. investigators.

In a study of 578 men with type 2 diabetes whose testosterone was measured during 2002-2004 and who were followed for 6 years, 36 of 182 diabetic men with untreated low testosterone (20%) died during the study period, compared with 31 of the 338 men (9%) with normal testosterone levels.

Meanwhile, 5 of the 58 diabetic men (8.6%) who were given testosterone replacement therapy died during the study, putting their mortality risk on par with diabetic men with normal testosterone levels. The study was presented at the annual meeting of the Society for Endocrinology in Birmingham, U.K., on April 12 and published online in Endocrine Abstracts (2011 April;25:P163).

Lead investigator Dr. T. Hugh Jones of Barnsley Hospital NHS Foundation Trust and the University of Sheffield (U.K.) said in an interview that while a prospective long-term study was still needed, the mortality difference shown in this retrospective study was "quite dramatic." The vast majority of deaths were from cardiovascular disease, Dr. Jones said, adding that this was to be expected with any diabetes mellitus population.

The mean age of the study subjects was 61 years, and the subjects were well matched, Dr. Jones and colleagues wrote. Survival was significantly decreased in patients with low testosterone who did not have replacement therapy, compared with those with normal testosterone levels. The treated group had significantly improved survival. In a Cox regression model adjusted for age, weight, hemoglobin A1c, pre-existing cardiovascular disease, smoking, and use of statins, ACE inhibitors, and angiotensin receptor blockers, the hazard ratio for all-cause mortality was 2.2 in participants with untreated low total testosterone, they wrote.

While the method and amount of testosterone replacement was not standardized in the study, the investigators treated each man to his normal physiologic range and not higher, Dr. Jones said. Overly high levels of testosterone replacement, he said, have been associated in the past with elevated cardiovascular risk.

Testosterone has been shown to have a range of biological actions, including anti-inflammatory effects, and Dr. Jones has in recent years investigated the role of testosterone in diabetes. Last year, Dr. Jones and his colleagues published evidence that low testosterone increases diabetes mortality risk in men; more recently, he and other investigators have looked at the broader effects of testosterone replacement therapy in diabetic men.

In a separate, randomized study by Dr. Jones and his colleagues in 220 hypogonadal men with type 2 diabetes and/or metabolic syndrome, use of a transdermal testosterone-replacement patch was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein A, and sexual health (Diabetes Care 2011;34:828-37).

Dr. Jones had no relevant disclosures.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

Prostate cancer screening in the general population is likely to reduce disease-specific deaths by less than a third, according to results from a 20-year Swedish study.

The findings, published March 31 in BMJ, involve the longest follow-up of any prostate cancer screening study to date, thanks in part to the ease of tracking Swedish patients through national databases and registries (BMJ 2011;342:d1539 [doi:10.1136/bmj.d1539]).

For their research, Dr. Gabriel Sandblom of the Karolinska Institute, Stockholm, and his colleagues examined results from a study enrolling 9,026 randomly selected men, aged 50-69 years, in Norrköping, Sweden. The study began in 1987, with every sixth man, or 1,494 in all, randomized to undergo prostate cancer screening every 3 years. The first two screenings used digital rectal examination only; in subsequent screenings, prostate-specific antigen testing was added. Men in the control group (n = 7,532) were not invited to be screened.

For the fourth and final screen in 1996, only subjects aged 69 years or under were invited. All men with cancer diagnosed up to Dec. 31, 1999, were included in the analysis, and survival was followed through the end of 2008.

The investigators found that more cancer was detected in the screened group (5.7%) than in the control group (3.9%), and that a significantly greater proportion of men in the screened group (56.5%) had localized tumors than in the control group (26.7%). Disease-specific mortality was 35% for men diagnosed in the screening group and 45% for controls; overall mortality for men with prostate cancer was 81% in the screening group and 86% in controls.

The risk ratio for death from prostate cancer was 1.16 (95% confidence interval 0.78-1.73), which the investigators noted was similar to that found in earlier, larger studies of shorter duration.

"The confidence interval of the risk ratio was narrow enough to conclude that screening and treatment of men with tumors detected through screening as practiced in the present study are unlikely to reduce mortality from prostate cancer by more than a third," they wrote. "Though screening could lead to a reduction of up to a third in mortality from prostate cancer, this would be at the risk of overdetection and overtreatment."

Dr. Sandblom and his colleagues recommended in their analysis that before undergoing prostate-specific antigen testing, "asymptomatic men should be informed about the potential hazards of treatment with curative intent in case prostate cancer is diagnosed." These hazards, they wrote, include erectile dysfunction, urinary incontinence, bowel symptoms, discomfort, and psychological stress.

The investigators cited as strengths of their study the low dropout rate; high compliance of their subjects; uniform treatment; complete data on tumor stage and grade; and detailed information on cause of death, thanks to comprehensive government registries and databases. The investigators acknowledged that although the size of the study population was not sufficient to draw definite conclusions, it was enough "to show major differences in prostate cancer–specific survival."

The study was funded by Swedish government agencies. Dr. Sandblom and his colleagues declared no conflicts of interest.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28 in the Journal of the American College of Cardiology (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial evidence available, update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.

• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

• The role of invasive therapy in patients with chronic kidney disease.

• The importance of participating in quality improvement processes.

• The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics "may diminish thrombus burden and ‘passivate’ unstable plaques," improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

"For patients not at high risk, a delayed invasive approach is also reasonable," Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies "more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy," due to concerns about the potential bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended.

People with kidney disease should receive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography. Finally, the guidelines recommend that clinicians and hospitals "participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI." No such recommendation had been included in the 2007 guidelines.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright’s coauthors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.