Jeff Evans

Health care services in the United States for adolescents are fragmented, leaving gaps in care that "safety-net" resources cannot fill, especially for those who are uninsured or vulnerable to risky behavior or poor health, according to a report issued by the Institute of Medicine and the National Research Council.

The report, "Adolescent Health Services: Missing Opportunities," calls on federal and state agencies, private foundations, and insurers to develop a health care system that fosters coordination between primary and specialty care, as well as a way for primary care services to reach adolescents in safety-net settings, such as hospitals, community- and school-based health centers, and youth development programs. The report defines adolescents as individuals 10–19 years of age.

"Adolescents have unique health needs, and our health system should not approach their care the same way it does children or adults," Dr. Robert S. Lawrence of Johns Hopkins University, Baltimore, said in a written statement. Dr. Lawrence is the chair of the 19-member committee that issued the report.

The Committee on Adolescent Health Care Services and Models of Care for Treatment, Prevention, and Healthy Development advised that disease prevention, health promotion, and behavioral health should be major components of routine health services. It also acknowledged that primary care providers will need adequate financial support from payment systems in order to manage and coordinate specialty services.

Public and private programs within communities will be required to manage referrals between providers of primary care services and other health services, the committee determined. Electronic health records could assist in this regard by providing opportunities for messaging, reminder services, and personalized health education services to improve interventions, especially for adolescents who may be most vulnerable to risky behavior or poor health. This population includes adolescents who are poor; are members of ethnic or racial minorities; are recent immigrants; are in foster care; are in the juvenile justice system; or are lesbian, gay, bisexual, or transgender.

The committee said that many of the existing specialty services in mental health, sexual and reproductive health, oral health, and substance abuse treatment "are not accessible to most adolescents, nor do they always meet the needs of many adolescents who receive care in safety-net settings," especially if confidentiality is not fully ensured.

The system of mental health services for adolescents is especially uncoordinated and fragmented because of financial barriers, gaps in eligibility, and concerns about confidentiality and privacy.

Throughout the report, committee members recommended that federal and state policy makers should continue to support laws that enable adolescents to give their own consent for health services and to receive services confidentially when necessary, such as for contraception, mental health care, and substance abuse treatment.

In the report, the committee proposed several options for federal and state policy makers to develop to ensure that all adolescents have comprehensive, continuous health insurance coverage:

▸ Require states to provide Medicaid or other forms of insurance coverage for vulnerable or underserved adolescents.

▸ Design and implement Medicaid and State Children's Health Insurance Program policies to increase enrollment and retention of eligible but uninsured adolescents.

▸ Improve incentives for private health insurers to provide coverage, such as by requiring school-based coverage and allowing nongroup policies tailored to adolescents.

Because physicians and other health care providers frequently lack the skills to interact effectively with adolescents, the report advised that those who serve adolescents should receive a "specific and detailed education in the nature of adolescents' health problems and have in their clinical repertoire a range of effective ways to treat and prevent disease in this age group, as well as to promote healthy behavior and lifestyles within a developmental framework." These skills should also be a part of the minimal set of competencies that need to be demonstrated for the licensing, certification, and accreditation of providers, according to the committee.

The report was sponsored by the Atlantic Philanthropies Ltd., an international charitable foundation.

Health care services in the United States for adolescents are fragmented, leaving gaps in care that "safety-net" resources cannot fill, especially for those who are uninsured or vulnerable to risky behavior or poor health, according to a report issued by the Institute of Medicine and the National Research Council.

The report, "Adolescent Health Services: Missing Opportunities," calls on federal and state agencies, private foundations, and insurers to develop a health care system that fosters coordination between primary and specialty care, as well as a way for primary care services to reach adolescents in safety-net settings, such as hospitals, community- and school-based health centers, and youth development programs. The report defines adolescents as individuals 10–19 years of age.

"Adolescents have unique health needs, and our health system should not approach their care the same way it does children or adults," Dr. Robert S. Lawrence of Johns Hopkins University, Baltimore, said in a written statement. Dr. Lawrence is the chair of the 19-member committee that issued the report.

The Committee on Adolescent Health Care Services and Models of Care for Treatment, Prevention, and Healthy Development advised that disease prevention, health promotion, and behavioral health should be major components of routine health services. It also acknowledged that primary care providers will need adequate financial support from payment systems in order to manage and coordinate specialty services.

Public and private programs within communities will be required to manage referrals between providers of primary care services and other health services, the committee determined. Electronic health records could assist in this regard by providing opportunities for messaging, reminder services, and personalized health education services to improve interventions, especially for adolescents who may be most vulnerable to risky behavior or poor health. This population includes adolescents who are poor; are members of ethnic or racial minorities; are recent immigrants; are in foster care; are in the juvenile justice system; or are lesbian, gay, bisexual, or transgender.

The committee said that many of the existing specialty services in mental health, sexual and reproductive health, oral health, and substance abuse treatment "are not accessible to most adolescents, nor do they always meet the needs of many adolescents who receive care in safety-net settings," especially if confidentiality is not fully ensured.

The system of mental health services for adolescents is especially uncoordinated and fragmented because of financial barriers, gaps in eligibility, and concerns about confidentiality and privacy.

Throughout the report, committee members recommended that federal and state policy makers should continue to support laws that enable adolescents to give their own consent for health services and to receive services confidentially when necessary, such as for contraception, mental health care, and substance abuse treatment.

In the report, the committee proposed several options for federal and state policy makers to develop to ensure that all adolescents have comprehensive, continuous health insurance coverage:

▸ Require states to provide Medicaid or other forms of insurance coverage for vulnerable or underserved adolescents.

▸ Design and implement Medicaid and State Children's Health Insurance Program policies to increase enrollment and retention of eligible but uninsured adolescents.

▸ Improve incentives for private health insurers to provide coverage, such as by requiring school-based coverage and allowing nongroup policies tailored to adolescents.

Because physicians and other health care providers frequently lack the skills to interact effectively with adolescents, the report advised that those who serve adolescents should receive a "specific and detailed education in the nature of adolescents' health problems and have in their clinical repertoire a range of effective ways to treat and prevent disease in this age group, as well as to promote healthy behavior and lifestyles within a developmental framework." These skills should also be a part of the minimal set of competencies that need to be demonstrated for the licensing, certification, and accreditation of providers, according to the committee.

The report was sponsored by the Atlantic Philanthropies Ltd., an international charitable foundation.

Health care services in the United States for adolescents are fragmented, leaving gaps in care that "safety-net" resources cannot fill, especially for those who are uninsured or vulnerable to risky behavior or poor health, according to a report issued by the Institute of Medicine and the National Research Council.

The report, "Adolescent Health Services: Missing Opportunities," calls on federal and state agencies, private foundations, and insurers to develop a health care system that fosters coordination between primary and specialty care, as well as a way for primary care services to reach adolescents in safety-net settings, such as hospitals, community- and school-based health centers, and youth development programs. The report defines adolescents as individuals 10–19 years of age.

"Adolescents have unique health needs, and our health system should not approach their care the same way it does children or adults," Dr. Robert S. Lawrence of Johns Hopkins University, Baltimore, said in a written statement. Dr. Lawrence is the chair of the 19-member committee that issued the report.

The Committee on Adolescent Health Care Services and Models of Care for Treatment, Prevention, and Healthy Development advised that disease prevention, health promotion, and behavioral health should be major components of routine health services. It also acknowledged that primary care providers will need adequate financial support from payment systems in order to manage and coordinate specialty services.

Public and private programs within communities will be required to manage referrals between providers of primary care services and other health services, the committee determined. Electronic health records could assist in this regard by providing opportunities for messaging, reminder services, and personalized health education services to improve interventions, especially for adolescents who may be most vulnerable to risky behavior or poor health. This population includes adolescents who are poor; are members of ethnic or racial minorities; are recent immigrants; are in foster care; are in the juvenile justice system; or are lesbian, gay, bisexual, or transgender.

The committee said that many of the existing specialty services in mental health, sexual and reproductive health, oral health, and substance abuse treatment "are not accessible to most adolescents, nor do they always meet the needs of many adolescents who receive care in safety-net settings," especially if confidentiality is not fully ensured.

The system of mental health services for adolescents is especially uncoordinated and fragmented because of financial barriers, gaps in eligibility, and concerns about confidentiality and privacy.

Throughout the report, committee members recommended that federal and state policy makers should continue to support laws that enable adolescents to give their own consent for health services and to receive services confidentially when necessary, such as for contraception, mental health care, and substance abuse treatment.

In the report, the committee proposed several options for federal and state policy makers to develop to ensure that all adolescents have comprehensive, continuous health insurance coverage:

▸ Require states to provide Medicaid or other forms of insurance coverage for vulnerable or underserved adolescents.

▸ Design and implement Medicaid and State Children's Health Insurance Program policies to increase enrollment and retention of eligible but uninsured adolescents.

▸ Improve incentives for private health insurers to provide coverage, such as by requiring school-based coverage and allowing nongroup policies tailored to adolescents.

Because physicians and other health care providers frequently lack the skills to interact effectively with adolescents, the report advised that those who serve adolescents should receive a "specific and detailed education in the nature of adolescents' health problems and have in their clinical repertoire a range of effective ways to treat and prevent disease in this age group, as well as to promote healthy behavior and lifestyles within a developmental framework." These skills should also be a part of the minimal set of competencies that need to be demonstrated for the licensing, certification, and accreditation of providers, according to the committee.

The report was sponsored by the Atlantic Philanthropies Ltd., an international charitable foundation.

The full report is available at www.cdc.gov/std/stats07

The rates of three major sexually transmitted diseases in the United States in 2007 continued to follow a nearly decade-long climb that has disproportionately affected minorities and women, according to a report issued by the Centers for Disease Control and Prevention.

These trends in infection rates of chlamydia, gonorrhea, and syphilis are “not new, but the fact that they are continuing at such a dramatic level is really the major area of concern,” said Dr. John M. Douglas Jr., director of the division of STD prevention at the CDC. All three STDs have long-standing federally funded control programs.

The report is compiled from surveillance data obtained from case reports from state and local STD programs, which included Regional Infertility Prevention Projects, the National Job Training Program, the Corrections STD Prevalence Monitoring Project, the Indian Health Service, and the Men Who Have Sex With Men (MSM) Prevalence Monitoring Project; the Gonococcal Isolate Surveillance Project; and national surveys implemented by federal and private organizations.

▸ Chlamydia. Since 1994, Chlamydia trachomatis infections have comprised the greatest percentage of all STDs reported to the CDC. This trend continued in 2007, with more than 1.1 million sexually transmitted cases of chlamydia reported to the CDC, making it the “most commonly reported notifiable [infectious] disease in the United States,” the report said.

Chlamydia infections rose 7.5% from 344 cases per 100,000 population in 2006 to 370 cases per 100,000 in 2007. This rate was roughly equal across the West, Midwest, South, and Northeast.

Chlamydia screening has increased since the late 1980s, especially in women, who are targeted for screening more often because of the risk of pelvic inflammatory disease (PID)—a major cause of infertility, ectopic pregnancy, and chronic pelvic pain—and passage of the infection to infants during delivery, which can cause neonatal ophthalmia and pneumonia.

In 2007, chlamydial infections were more commonly reported in women (544 cases per 100,000) than in men (190 cases per 100,000), but the number of cases in men during 2003-2007 grew faster than it did in women (43% vs. 17%, respectively). Chlamydia disproportionately infected black women aged 15-19 at a higher rate than any other group; they had a rate of 9,647 cases per 100,000.

The median prevalence of chlamydia across the states and territories was high in various selected screening populations, including family planning clinics (6.9%) and prenatal clinics (7.4%). Median rates across the states and territories were similarly high among economically disadvantaged men and women in the National Job Training Program (7.2% and 13.2%, respectively) and among adolescent males and females entering juvenile detention centers (5.7% and 14.3%, respectively).

“The continued increase in chlamydia case reports in 2007 most likely represents a continued increase in screening for this infection, more sensitive tests, and more complete national reporting, but it may also reflect a true increase in morbidity,” the report said.

The CDC recommends annual chlamydia screening for all sexually active women younger than age 26 years. “However, many women who are at risk are still not being tested, reflecting, in part, lack of awareness among some health care providers and limited resources available to support screening,” the agency said. Full compliance of this age group in annual chlamydia screening “could be the single most impactful thing we could do to really turn the STD epidemic around,” Dr. Douglas said.

▸ Gonorrhea. Although cases of gonorrhea dropped 74% from 1975 to 1997, recent years have seen a leveling off of the rates of the disease, which in 2007 were 114 per 100,000 for men and 124 per 100,000 for women. Overall, the CDC collected 355,991 case reports of gonorrhea in 2007. For the last 6 years, women have had a higher rate of the disease than men. Gonococcal infections, like chlamydia, also are a major cause of PID in women.

A wide gulf continued to separate the rates of gonorrhea in black and white individuals. In 2007, the rate of the STD was 26 times higher in black men than in it was in white men. Black women had a 13-fold higher rate of gonorrhea than did white women. Black women aged 15-19 years also had the highest rate of gonorrhea of any group (2,956 per 100,000).

And even though blacks comprise just 12% of the U.S. population, they accounted for about 70% of all cases of gonorrhea. “It's likely that some part of the disparity is related to the fact that African American populations are more likely to be tested in public clinics, and public clinics are more likely to have higher levels of reporting than private clinics and laboratories. However, when we look at other sorts of surveillance data, we see those same disparities,” he said.

The high prevalence of STDs in African American communities makes it more likely that a person will meet a new sexual partner with an infection. A big part of high prevalence may be due to social conditions, including a lack of access to good and timely health care, and relatively high levels of poverty and incarceration, Dr. Douglas said.

The South, which perennially has the highest rate of gonorrhea, had an increase in cases of about 5% between 2003 and 2006, but saw no change in 2007. Rates held relatively steady in the Northeast and Midwest during 2003-2007. The rate of gonorrhea in the West declined slightly in 2007 after it increased 29% during 2003-2006.

▸ Syphilis. The rate of primary and secondary syphilis went into a steep, 90% decline during the 1990s and in 2000 reached the lowest rate of the disease that has been reported since 1941. But the rate of primary and secondary syphilis has increased 81% from 2.1 cases per 100,000 in 2001 to 3.8 cases per 100,000 in 2007. Nationally, 11,466 cases were reported to the CDC in 2007. The rate of congenital syphilis grew by 28% during 2005-2007, with 339 reported cases in 2005 and 430 in 2007.

Disparities in syphilis rates have shrunk for black individuals from 29 times the rate in whites in 1999 to 7 times the rate in whites in 2007. But the disparity has been widening again since 2003.

While the South and urban areas of other regions maintain most of the U.S. burden of primary and secondary syphilis, the estimated proportion of cases attributable to MSM rose from 4% in 2000 to 62% in 2004. This estimate increased to 65% in 2007 after the CDC requested in 2005 that all state health departments report the gender of sex partners for people with syphilis.

Even though many syphilis infections in MSM are being transmitted inside the boundaries of relationships in which both partners are known to be HIV-infected, syphilis can still produce substantial morbidity in this group, Dr. Douglas noted.

ELSEVIER GLOBAL MEDICAL NEWS

'The fact that [increases in STD rates] are continuing at such a dramatic level is really the major area of concern.' DR. DOUGLAS

The full report is available at www.cdc.gov/std/stats07

The rates of three major sexually transmitted diseases in the United States in 2007 continued to follow a nearly decade-long climb that has disproportionately affected minorities and women, according to a report issued by the Centers for Disease Control and Prevention.

These trends in infection rates of chlamydia, gonorrhea, and syphilis are “not new, but the fact that they are continuing at such a dramatic level is really the major area of concern,” said Dr. John M. Douglas Jr., director of the division of STD prevention at the CDC. All three STDs have long-standing federally funded control programs.

The report is compiled from surveillance data obtained from case reports from state and local STD programs, which included Regional Infertility Prevention Projects, the National Job Training Program, the Corrections STD Prevalence Monitoring Project, the Indian Health Service, and the Men Who Have Sex With Men (MSM) Prevalence Monitoring Project; the Gonococcal Isolate Surveillance Project; and national surveys implemented by federal and private organizations.

▸ Chlamydia. Since 1994, Chlamydia trachomatis infections have comprised the greatest percentage of all STDs reported to the CDC. This trend continued in 2007, with more than 1.1 million sexually transmitted cases of chlamydia reported to the CDC, making it the “most commonly reported notifiable [infectious] disease in the United States,” the report said.

Chlamydia infections rose 7.5% from 344 cases per 100,000 population in 2006 to 370 cases per 100,000 in 2007. This rate was roughly equal across the West, Midwest, South, and Northeast.

Chlamydia screening has increased since the late 1980s, especially in women, who are targeted for screening more often because of the risk of pelvic inflammatory disease (PID)—a major cause of infertility, ectopic pregnancy, and chronic pelvic pain—and passage of the infection to infants during delivery, which can cause neonatal ophthalmia and pneumonia.

In 2007, chlamydial infections were more commonly reported in women (544 cases per 100,000) than in men (190 cases per 100,000), but the number of cases in men during 2003-2007 grew faster than it did in women (43% vs. 17%, respectively). Chlamydia disproportionately infected black women aged 15-19 at a higher rate than any other group; they had a rate of 9,647 cases per 100,000.

The median prevalence of chlamydia across the states and territories was high in various selected screening populations, including family planning clinics (6.9%) and prenatal clinics (7.4%). Median rates across the states and territories were similarly high among economically disadvantaged men and women in the National Job Training Program (7.2% and 13.2%, respectively) and among adolescent males and females entering juvenile detention centers (5.7% and 14.3%, respectively).

“The continued increase in chlamydia case reports in 2007 most likely represents a continued increase in screening for this infection, more sensitive tests, and more complete national reporting, but it may also reflect a true increase in morbidity,” the report said.

The CDC recommends annual chlamydia screening for all sexually active women younger than age 26 years. “However, many women who are at risk are still not being tested, reflecting, in part, lack of awareness among some health care providers and limited resources available to support screening,” the agency said. Full compliance of this age group in annual chlamydia screening “could be the single most impactful thing we could do to really turn the STD epidemic around,” Dr. Douglas said.

▸ Gonorrhea. Although cases of gonorrhea dropped 74% from 1975 to 1997, recent years have seen a leveling off of the rates of the disease, which in 2007 were 114 per 100,000 for men and 124 per 100,000 for women. Overall, the CDC collected 355,991 case reports of gonorrhea in 2007. For the last 6 years, women have had a higher rate of the disease than men. Gonococcal infections, like chlamydia, also are a major cause of PID in women.

A wide gulf continued to separate the rates of gonorrhea in black and white individuals. In 2007, the rate of the STD was 26 times higher in black men than in it was in white men. Black women had a 13-fold higher rate of gonorrhea than did white women. Black women aged 15-19 years also had the highest rate of gonorrhea of any group (2,956 per 100,000).

And even though blacks comprise just 12% of the U.S. population, they accounted for about 70% of all cases of gonorrhea. “It's likely that some part of the disparity is related to the fact that African American populations are more likely to be tested in public clinics, and public clinics are more likely to have higher levels of reporting than private clinics and laboratories. However, when we look at other sorts of surveillance data, we see those same disparities,” he said.

The high prevalence of STDs in African American communities makes it more likely that a person will meet a new sexual partner with an infection. A big part of high prevalence may be due to social conditions, including a lack of access to good and timely health care, and relatively high levels of poverty and incarceration, Dr. Douglas said.

The South, which perennially has the highest rate of gonorrhea, had an increase in cases of about 5% between 2003 and 2006, but saw no change in 2007. Rates held relatively steady in the Northeast and Midwest during 2003-2007. The rate of gonorrhea in the West declined slightly in 2007 after it increased 29% during 2003-2006.

▸ Syphilis. The rate of primary and secondary syphilis went into a steep, 90% decline during the 1990s and in 2000 reached the lowest rate of the disease that has been reported since 1941. But the rate of primary and secondary syphilis has increased 81% from 2.1 cases per 100,000 in 2001 to 3.8 cases per 100,000 in 2007. Nationally, 11,466 cases were reported to the CDC in 2007. The rate of congenital syphilis grew by 28% during 2005-2007, with 339 reported cases in 2005 and 430 in 2007.

Disparities in syphilis rates have shrunk for black individuals from 29 times the rate in whites in 1999 to 7 times the rate in whites in 2007. But the disparity has been widening again since 2003.

While the South and urban areas of other regions maintain most of the U.S. burden of primary and secondary syphilis, the estimated proportion of cases attributable to MSM rose from 4% in 2000 to 62% in 2004. This estimate increased to 65% in 2007 after the CDC requested in 2005 that all state health departments report the gender of sex partners for people with syphilis.

Even though many syphilis infections in MSM are being transmitted inside the boundaries of relationships in which both partners are known to be HIV-infected, syphilis can still produce substantial morbidity in this group, Dr. Douglas noted.

ELSEVIER GLOBAL MEDICAL NEWS

'The fact that [increases in STD rates] are continuing at such a dramatic level is really the major area of concern.' DR. DOUGLAS

The full report is available at www.cdc.gov/std/stats07

The rates of three major sexually transmitted diseases in the United States in 2007 continued to follow a nearly decade-long climb that has disproportionately affected minorities and women, according to a report issued by the Centers for Disease Control and Prevention.

These trends in infection rates of chlamydia, gonorrhea, and syphilis are “not new, but the fact that they are continuing at such a dramatic level is really the major area of concern,” said Dr. John M. Douglas Jr., director of the division of STD prevention at the CDC. All three STDs have long-standing federally funded control programs.

The report is compiled from surveillance data obtained from case reports from state and local STD programs, which included Regional Infertility Prevention Projects, the National Job Training Program, the Corrections STD Prevalence Monitoring Project, the Indian Health Service, and the Men Who Have Sex With Men (MSM) Prevalence Monitoring Project; the Gonococcal Isolate Surveillance Project; and national surveys implemented by federal and private organizations.

▸ Chlamydia. Since 1994, Chlamydia trachomatis infections have comprised the greatest percentage of all STDs reported to the CDC. This trend continued in 2007, with more than 1.1 million sexually transmitted cases of chlamydia reported to the CDC, making it the “most commonly reported notifiable [infectious] disease in the United States,” the report said.

Chlamydia infections rose 7.5% from 344 cases per 100,000 population in 2006 to 370 cases per 100,000 in 2007. This rate was roughly equal across the West, Midwest, South, and Northeast.

Chlamydia screening has increased since the late 1980s, especially in women, who are targeted for screening more often because of the risk of pelvic inflammatory disease (PID)—a major cause of infertility, ectopic pregnancy, and chronic pelvic pain—and passage of the infection to infants during delivery, which can cause neonatal ophthalmia and pneumonia.

In 2007, chlamydial infections were more commonly reported in women (544 cases per 100,000) than in men (190 cases per 100,000), but the number of cases in men during 2003-2007 grew faster than it did in women (43% vs. 17%, respectively). Chlamydia disproportionately infected black women aged 15-19 at a higher rate than any other group; they had a rate of 9,647 cases per 100,000.

The median prevalence of chlamydia across the states and territories was high in various selected screening populations, including family planning clinics (6.9%) and prenatal clinics (7.4%). Median rates across the states and territories were similarly high among economically disadvantaged men and women in the National Job Training Program (7.2% and 13.2%, respectively) and among adolescent males and females entering juvenile detention centers (5.7% and 14.3%, respectively).

“The continued increase in chlamydia case reports in 2007 most likely represents a continued increase in screening for this infection, more sensitive tests, and more complete national reporting, but it may also reflect a true increase in morbidity,” the report said.

The CDC recommends annual chlamydia screening for all sexually active women younger than age 26 years. “However, many women who are at risk are still not being tested, reflecting, in part, lack of awareness among some health care providers and limited resources available to support screening,” the agency said. Full compliance of this age group in annual chlamydia screening “could be the single most impactful thing we could do to really turn the STD epidemic around,” Dr. Douglas said.

▸ Gonorrhea. Although cases of gonorrhea dropped 74% from 1975 to 1997, recent years have seen a leveling off of the rates of the disease, which in 2007 were 114 per 100,000 for men and 124 per 100,000 for women. Overall, the CDC collected 355,991 case reports of gonorrhea in 2007. For the last 6 years, women have had a higher rate of the disease than men. Gonococcal infections, like chlamydia, also are a major cause of PID in women.

A wide gulf continued to separate the rates of gonorrhea in black and white individuals. In 2007, the rate of the STD was 26 times higher in black men than in it was in white men. Black women had a 13-fold higher rate of gonorrhea than did white women. Black women aged 15-19 years also had the highest rate of gonorrhea of any group (2,956 per 100,000).

And even though blacks comprise just 12% of the U.S. population, they accounted for about 70% of all cases of gonorrhea. “It's likely that some part of the disparity is related to the fact that African American populations are more likely to be tested in public clinics, and public clinics are more likely to have higher levels of reporting than private clinics and laboratories. However, when we look at other sorts of surveillance data, we see those same disparities,” he said.

The high prevalence of STDs in African American communities makes it more likely that a person will meet a new sexual partner with an infection. A big part of high prevalence may be due to social conditions, including a lack of access to good and timely health care, and relatively high levels of poverty and incarceration, Dr. Douglas said.

The South, which perennially has the highest rate of gonorrhea, had an increase in cases of about 5% between 2003 and 2006, but saw no change in 2007. Rates held relatively steady in the Northeast and Midwest during 2003-2007. The rate of gonorrhea in the West declined slightly in 2007 after it increased 29% during 2003-2006.

▸ Syphilis. The rate of primary and secondary syphilis went into a steep, 90% decline during the 1990s and in 2000 reached the lowest rate of the disease that has been reported since 1941. But the rate of primary and secondary syphilis has increased 81% from 2.1 cases per 100,000 in 2001 to 3.8 cases per 100,000 in 2007. Nationally, 11,466 cases were reported to the CDC in 2007. The rate of congenital syphilis grew by 28% during 2005-2007, with 339 reported cases in 2005 and 430 in 2007.

Disparities in syphilis rates have shrunk for black individuals from 29 times the rate in whites in 1999 to 7 times the rate in whites in 2007. But the disparity has been widening again since 2003.

While the South and urban areas of other regions maintain most of the U.S. burden of primary and secondary syphilis, the estimated proportion of cases attributable to MSM rose from 4% in 2000 to 62% in 2004. This estimate increased to 65% in 2007 after the CDC requested in 2005 that all state health departments report the gender of sex partners for people with syphilis.

Even though many syphilis infections in MSM are being transmitted inside the boundaries of relationships in which both partners are known to be HIV-infected, syphilis can still produce substantial morbidity in this group, Dr. Douglas noted.

ELSEVIER GLOBAL MEDICAL NEWS

'The fact that [increases in STD rates] are continuing at such a dramatic level is really the major area of concern.' DR. DOUGLAS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years (range of 25–86 years). Some had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“The lack of the fracture data doesn't concern me particularly in this population because of the really robust fracture reduction data that we've seen in postmenopausal women,” he said.

Zoledronic acid is available as a 5-mg dose in a 100-mL ready-to-infuse solution. It has been used by more than 164,000 patients since the FDA approved it in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years (range of 25–86 years). Some had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“The lack of the fracture data doesn't concern me particularly in this population because of the really robust fracture reduction data that we've seen in postmenopausal women,” he said.

Zoledronic acid is available as a 5-mg dose in a 100-mL ready-to-infuse solution. It has been used by more than 164,000 patients since the FDA approved it in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years (range of 25–86 years). Some had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“The lack of the fracture data doesn't concern me particularly in this population because of the really robust fracture reduction data that we've seen in postmenopausal women,” he said.

Zoledronic acid is available as a 5-mg dose in a 100-mL ready-to-infuse solution. It has been used by more than 164,000 patients since the FDA approved it in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

WASHINGTON — Advanced imaging methods with MRI and magnetoencephalography may be able to detect mild traumatic brain injury with greater accuracy than can conventional imaging techniques, according to two prospective pilot studies.

Conventional MR and CT neuroimaging focus on the detection of bleeding, which is only indirectly related to axonal injury. These methods are not able to detect about 70%–80% of mild to moderate traumatic brain injuries (TBIs), according to Mingxiong Huang, Ph.D., of the University of California, San Diego, and his colleagues.

Dr. Huang and his coinvestigators are finding that the combination of diffusion-tensor imaging (DTI) and magnetoencephalography (MEG) can reveal axonal injury resulting from tissue shearing and stretching, which is a leading cause of persistent postconcussive symptoms in mild TBI patients.

MEG pinpoints the temporal and spatial activation of neurons in the brain based on the tiny magnetic fields created by neuronal currents in cortical gray matter. DTI measures the pattern and direction of the movement of water molecules through white matter fiber tracts, which become disturbed after a TBI.

Detecting mild TBI is clinically important, Dr. Huang said, because even though roughly 85% of patients with mild TBI will be symptom free by 6 months, the remaining 15% have lingering cognitive and behavioral problems, and have a higher risk for developing epilepsy, severe depression, and dementia.

He and his colleagues studied 18 civilian and military patients with a closed-head injury and mild to moderate symptoms of TBI, along with 17 healthy control patients. None of the patients had visible lesions on conventional MRI or CT. In the patients with TBI symptoms, the researchers found that the location of neurons generating abnormal low-frequency delta waves that were seen on MEG was significantly correlated with the deafferentation of the underlying white matter fiber tracts on DTI. These findings were consistent with the patients' symptoms and the results of neuropsychological exams, and they help to confirm the hypothesis that pathological low-frequency delta waves are caused by the shearing of white matter fiber tracts, Dr. Huang reported at the annual meeting of the Society for Neuroscience.

MEG may be a more sensitive measure for mild TBI than is DTI because in some instances MEG was able to detect pathological low-frequency delta waves when DTI signals in white matter fiber tracts were within normal range, according to Dr. Huang. He also noted that the two modalities could be used to objectively monitor the effect of an intervention and provide prognostic information.

The investigators hope to expand their research by performing a longitudinal study in children that compares their recovery from mild TBI with the recovery of adults. In military personnel, the researchers would like to know how to differentiate the signs and symptoms of mild TBI from those of posttraumatic stress disorder. Both conditions have similar signs and symptoms and coincide in a subpopulation of patients, but the treatments for them are different.

In another study presented at the meeting, Andrew Maudsley, Ph.D., of the University of Miami and his colleagues used magnetic resonance spectroscopic imaging (MRSI) to detect the changes in brain metabolism that are indicative of mild TBI in patients with postconcussive symptoms.

The researchers used a volumetric acquisition method to obtain data on the whole brain rather than on just a single area, which is beneficial in imaging diffuse brain injury, according to Dr. Maudsley.

“If you used a conventional MRS method, which is a single voxel method, you have to [focus on] one brain region. You could very clearly choose a brain region, especially with mild injury, that actually looks normal on spectroscopy,” he said in an interview.

The investigators measured levels of N-acetylaspartate, creatine, and choline in the brain. The pilot study compared the average of all measured values from 22 patients who were classified as having mild brain injury with the average values from 67 age-matched controls. MRSI scans took place a median of 21 days after the patients' injuries, which were caused by motor vehicle accidents (17), falls (2), or assault (3).

Assessments of the group averages revealed that brain injury was associated with a significantly decreased level of N-acetylaspartate (a marker of neuronal and axonal viability), as well as an increased level of choline (a marker of membrane metabolism). The ratio of choline to N-acetylaspartate was the most sensitive marker for injury.

Overall, 90% of the patients had small and well-localized lesions on normal MRI, findings that are typical for mild TBI. But on MRSI, the researchers found widespread metabolite alterations throughout the cerebrum.

The patients' scores on neuropsychological tests were significantly correlated mostly with metabolite changes in the right frontal region. In one patient who underwent follow-up scans, the concentrations of N-acetylaspartate and choline continued to change significantly at 7 and 15 months post injury.

Dr. Maudsley said that he and his team hope to obtain longitudinal assessments of metabolite levels to determine if their short-term levels can predict future outcomes of patients with mild TBI. Outcomes at 6 months in close to half of the patients have shown some correlations between metabolite levels and scores on neuropsychological tests, he said.

“It's my feeling that these metabolites really take several days, if not a couple of weeks, to change. In the one example in which we had a more severe injury, things were actually worse at 6 months than they were at 5 weeks,” he added.

The use of the 3-tesla MR scanners that Dr. Maudsley and his associates used in their study is beginning to extend beyond academic medical centers and into regular clinics, especially for brain MRI applications.

Neither Dr. Huang nor Dr. Maudsley had conflicts of interest to report.

Magnetic resonance spectroscopic imaging of the brains of 18 traumatic brain injury patients (bottom three rows) show widespread alterations in the ratio of choline to N-acetyl aspartate (light blue to green color), unlike the brains of 6 control subjects (top row). Images courtesy Dr. Andrew A. Maudsley

WASHINGTON — Advanced imaging methods with MRI and magnetoencephalography may be able to detect mild traumatic brain injury with greater accuracy than can conventional imaging techniques, according to two prospective pilot studies.

Conventional MR and CT neuroimaging focus on the detection of bleeding, which is only indirectly related to axonal injury. These methods are not able to detect about 70%–80% of mild to moderate traumatic brain injuries (TBIs), according to Mingxiong Huang, Ph.D., of the University of California, San Diego, and his colleagues.

Dr. Huang and his coinvestigators are finding that the combination of diffusion-tensor imaging (DTI) and magnetoencephalography (MEG) can reveal axonal injury resulting from tissue shearing and stretching, which is a leading cause of persistent postconcussive symptoms in mild TBI patients.

MEG pinpoints the temporal and spatial activation of neurons in the brain based on the tiny magnetic fields created by neuronal currents in cortical gray matter. DTI measures the pattern and direction of the movement of water molecules through white matter fiber tracts, which become disturbed after a TBI.

Detecting mild TBI is clinically important, Dr. Huang said, because even though roughly 85% of patients with mild TBI will be symptom free by 6 months, the remaining 15% have lingering cognitive and behavioral problems, and have a higher risk for developing epilepsy, severe depression, and dementia.

He and his colleagues studied 18 civilian and military patients with a closed-head injury and mild to moderate symptoms of TBI, along with 17 healthy control patients. None of the patients had visible lesions on conventional MRI or CT. In the patients with TBI symptoms, the researchers found that the location of neurons generating abnormal low-frequency delta waves that were seen on MEG was significantly correlated with the deafferentation of the underlying white matter fiber tracts on DTI. These findings were consistent with the patients' symptoms and the results of neuropsychological exams, and they help to confirm the hypothesis that pathological low-frequency delta waves are caused by the shearing of white matter fiber tracts, Dr. Huang reported at the annual meeting of the Society for Neuroscience.

MEG may be a more sensitive measure for mild TBI than is DTI because in some instances MEG was able to detect pathological low-frequency delta waves when DTI signals in white matter fiber tracts were within normal range, according to Dr. Huang. He also noted that the two modalities could be used to objectively monitor the effect of an intervention and provide prognostic information.

The investigators hope to expand their research by performing a longitudinal study in children that compares their recovery from mild TBI with the recovery of adults. In military personnel, the researchers would like to know how to differentiate the signs and symptoms of mild TBI from those of posttraumatic stress disorder. Both conditions have similar signs and symptoms and coincide in a subpopulation of patients, but the treatments for them are different.

In another study presented at the meeting, Andrew Maudsley, Ph.D., of the University of Miami and his colleagues used magnetic resonance spectroscopic imaging (MRSI) to detect the changes in brain metabolism that are indicative of mild TBI in patients with postconcussive symptoms.

The researchers used a volumetric acquisition method to obtain data on the whole brain rather than on just a single area, which is beneficial in imaging diffuse brain injury, according to Dr. Maudsley.

“If you used a conventional MRS method, which is a single voxel method, you have to [focus on] one brain region. You could very clearly choose a brain region, especially with mild injury, that actually looks normal on spectroscopy,” he said in an interview.

The investigators measured levels of N-acetylaspartate, creatine, and choline in the brain. The pilot study compared the average of all measured values from 22 patients who were classified as having mild brain injury with the average values from 67 age-matched controls. MRSI scans took place a median of 21 days after the patients' injuries, which were caused by motor vehicle accidents (17), falls (2), or assault (3).

Assessments of the group averages revealed that brain injury was associated with a significantly decreased level of N-acetylaspartate (a marker of neuronal and axonal viability), as well as an increased level of choline (a marker of membrane metabolism). The ratio of choline to N-acetylaspartate was the most sensitive marker for injury.

Overall, 90% of the patients had small and well-localized lesions on normal MRI, findings that are typical for mild TBI. But on MRSI, the researchers found widespread metabolite alterations throughout the cerebrum.

The patients' scores on neuropsychological tests were significantly correlated mostly with metabolite changes in the right frontal region. In one patient who underwent follow-up scans, the concentrations of N-acetylaspartate and choline continued to change significantly at 7 and 15 months post injury.

Dr. Maudsley said that he and his team hope to obtain longitudinal assessments of metabolite levels to determine if their short-term levels can predict future outcomes of patients with mild TBI. Outcomes at 6 months in close to half of the patients have shown some correlations between metabolite levels and scores on neuropsychological tests, he said.

“It's my feeling that these metabolites really take several days, if not a couple of weeks, to change. In the one example in which we had a more severe injury, things were actually worse at 6 months than they were at 5 weeks,” he added.

The use of the 3-tesla MR scanners that Dr. Maudsley and his associates used in their study is beginning to extend beyond academic medical centers and into regular clinics, especially for brain MRI applications.

Neither Dr. Huang nor Dr. Maudsley had conflicts of interest to report.

Magnetic resonance spectroscopic imaging of the brains of 18 traumatic brain injury patients (bottom three rows) show widespread alterations in the ratio of choline to N-acetyl aspartate (light blue to green color), unlike the brains of 6 control subjects (top row). Images courtesy Dr. Andrew A. Maudsley

WASHINGTON — Advanced imaging methods with MRI and magnetoencephalography may be able to detect mild traumatic brain injury with greater accuracy than can conventional imaging techniques, according to two prospective pilot studies.

Conventional MR and CT neuroimaging focus on the detection of bleeding, which is only indirectly related to axonal injury. These methods are not able to detect about 70%–80% of mild to moderate traumatic brain injuries (TBIs), according to Mingxiong Huang, Ph.D., of the University of California, San Diego, and his colleagues.

Dr. Huang and his coinvestigators are finding that the combination of diffusion-tensor imaging (DTI) and magnetoencephalography (MEG) can reveal axonal injury resulting from tissue shearing and stretching, which is a leading cause of persistent postconcussive symptoms in mild TBI patients.

MEG pinpoints the temporal and spatial activation of neurons in the brain based on the tiny magnetic fields created by neuronal currents in cortical gray matter. DTI measures the pattern and direction of the movement of water molecules through white matter fiber tracts, which become disturbed after a TBI.

Detecting mild TBI is clinically important, Dr. Huang said, because even though roughly 85% of patients with mild TBI will be symptom free by 6 months, the remaining 15% have lingering cognitive and behavioral problems, and have a higher risk for developing epilepsy, severe depression, and dementia.

He and his colleagues studied 18 civilian and military patients with a closed-head injury and mild to moderate symptoms of TBI, along with 17 healthy control patients. None of the patients had visible lesions on conventional MRI or CT. In the patients with TBI symptoms, the researchers found that the location of neurons generating abnormal low-frequency delta waves that were seen on MEG was significantly correlated with the deafferentation of the underlying white matter fiber tracts on DTI. These findings were consistent with the patients' symptoms and the results of neuropsychological exams, and they help to confirm the hypothesis that pathological low-frequency delta waves are caused by the shearing of white matter fiber tracts, Dr. Huang reported at the annual meeting of the Society for Neuroscience.

MEG may be a more sensitive measure for mild TBI than is DTI because in some instances MEG was able to detect pathological low-frequency delta waves when DTI signals in white matter fiber tracts were within normal range, according to Dr. Huang. He also noted that the two modalities could be used to objectively monitor the effect of an intervention and provide prognostic information.

The investigators hope to expand their research by performing a longitudinal study in children that compares their recovery from mild TBI with the recovery of adults. In military personnel, the researchers would like to know how to differentiate the signs and symptoms of mild TBI from those of posttraumatic stress disorder. Both conditions have similar signs and symptoms and coincide in a subpopulation of patients, but the treatments for them are different.

In another study presented at the meeting, Andrew Maudsley, Ph.D., of the University of Miami and his colleagues used magnetic resonance spectroscopic imaging (MRSI) to detect the changes in brain metabolism that are indicative of mild TBI in patients with postconcussive symptoms.

The researchers used a volumetric acquisition method to obtain data on the whole brain rather than on just a single area, which is beneficial in imaging diffuse brain injury, according to Dr. Maudsley.

“If you used a conventional MRS method, which is a single voxel method, you have to [focus on] one brain region. You could very clearly choose a brain region, especially with mild injury, that actually looks normal on spectroscopy,” he said in an interview.

The investigators measured levels of N-acetylaspartate, creatine, and choline in the brain. The pilot study compared the average of all measured values from 22 patients who were classified as having mild brain injury with the average values from 67 age-matched controls. MRSI scans took place a median of 21 days after the patients' injuries, which were caused by motor vehicle accidents (17), falls (2), or assault (3).

Assessments of the group averages revealed that brain injury was associated with a significantly decreased level of N-acetylaspartate (a marker of neuronal and axonal viability), as well as an increased level of choline (a marker of membrane metabolism). The ratio of choline to N-acetylaspartate was the most sensitive marker for injury.

Overall, 90% of the patients had small and well-localized lesions on normal MRI, findings that are typical for mild TBI. But on MRSI, the researchers found widespread metabolite alterations throughout the cerebrum.

The patients' scores on neuropsychological tests were significantly correlated mostly with metabolite changes in the right frontal region. In one patient who underwent follow-up scans, the concentrations of N-acetylaspartate and choline continued to change significantly at 7 and 15 months post injury.

Dr. Maudsley said that he and his team hope to obtain longitudinal assessments of metabolite levels to determine if their short-term levels can predict future outcomes of patients with mild TBI. Outcomes at 6 months in close to half of the patients have shown some correlations between metabolite levels and scores on neuropsychological tests, he said.

“It's my feeling that these metabolites really take several days, if not a couple of weeks, to change. In the one example in which we had a more severe injury, things were actually worse at 6 months than they were at 5 weeks,” he added.

The use of the 3-tesla MR scanners that Dr. Maudsley and his associates used in their study is beginning to extend beyond academic medical centers and into regular clinics, especially for brain MRI applications.

Neither Dr. Huang nor Dr. Maudsley had conflicts of interest to report.

Magnetic resonance spectroscopic imaging of the brains of 18 traumatic brain injury patients (bottom three rows) show widespread alterations in the ratio of choline to N-acetyl aspartate (light blue to green color), unlike the brains of 6 control subjects (top row). Images courtesy Dr. Andrew A. Maudsley

WASHINGTON — The risk of adverse events such as major bleeding during elective coronary artery stenting is significantly lower when the procedure is performed with bivalirudin antithrombotic monotherapy than with other combinations based on unfractionated heparin, according to two Italian randomized trials.

The antithrombotic effects of bivalirudin have been shown to reduce bleeding rates after percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) alone, but few data exist that compare bivalirudin monotherapy with UFH in combination with a glycoprotein (GP) IIb/IIIa inhibitor such as tirofiban (Aggrastat) or with the heparin-reversing drug protamine.

One of bivalirudin's advantages over UFH is its short, 25-minute half-life. Investigators in the ARNO (Antithrombotic Regimens and Outcome) trial tried to see if this advantage could be equalized by administering protamine immediately after PCI to reverse the effects of UFH.

The ARNO trial featured 850 patients who were randomized to bivalirudin (Angiomax) or UFH plus protamine. Patients in both arms had a mean age of about 69 years; 22% had diabetes.

Bivalirudin monotherapy was associated with significantly fewer in-hospital major bleeding events than was therapy with UFH and protamine (0.5% and 2.1%, respectively). At 1 month after the procedure, bivalirudin still was associated with significantly fewer major bleeding events (0.9% vs. 2.8%), Dr. David Antoniucci reported at Transcatheter Cardiovascular Therapeutic 2008.

The combined rate of MI, target vessel revascularization, and death at 1 month was significantly lower in bivalirudin-treated patients (2.8%) than in heparin-treated patients (6.4%), said Dr. Antoniucci of the cardiology division at Careggi Hospital, Florence, Italy.

The second trial presented was conducted to determine the safety of bivalirudin in diabetic patients undergoing PCI by Dr. Carlo Briguori and his coinvestigators in the interventional cardiology laboratory at Clinica Mediterranea, Naples, Italy. They randomized 335 diabetic patients with an average age of about 65 years to treatment with either bivalirudin alone or UFH plus tirofiban. Aspirin and clopidogrel (Plavix) were given before the procedure to all patients in the trial, called NAPLES (Novel Approaches for Preventing or Limiting Event Study). The severity of bleeding risk was distributed similarly in both groups of diabetic patients.

Despite having diabetes, only 13% of the patients had multivessel disease. Only 11%-19% of the patients had unstable angina. None had acute coronary syndrome with elevated biomarkers.

Bivalirudin was associated with a significantly lower rate of adverse clinical events than was UFH plus tirofiban (12% vs. 21%, respectively). The difference was due primarily to a significantly higher rate of bleeding of 8% in the combination therapy patients, compared with the 2% rate in bivalirudin-treated patients.

In both ARNO and NAPLES, patients received aspirin and clopidogrel before undergoing PCI. Bivalirudin was administered in a single 0.75-mg/kg IV bolus, followed by an infusion of 1.75 mg/kg per hour during PCI. Patients in the NAPLES trial received 70 U/kg UFH, followed by additional boluses if their activated clotting time was less than 250 seconds, whereas those in the ARNO trial initially received 100 U/kg UFH.

Both Dr. Antoniucci and Dr. Briguori reported having no financial conflicts of interest related to their studies.

WASHINGTON — The risk of adverse events such as major bleeding during elective coronary artery stenting is significantly lower when the procedure is performed with bivalirudin antithrombotic monotherapy than with other combinations based on unfractionated heparin, according to two Italian randomized trials.

The antithrombotic effects of bivalirudin have been shown to reduce bleeding rates after percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) alone, but few data exist that compare bivalirudin monotherapy with UFH in combination with a glycoprotein (GP) IIb/IIIa inhibitor such as tirofiban (Aggrastat) or with the heparin-reversing drug protamine.

One of bivalirudin's advantages over UFH is its short, 25-minute half-life. Investigators in the ARNO (Antithrombotic Regimens and Outcome) trial tried to see if this advantage could be equalized by administering protamine immediately after PCI to reverse the effects of UFH.

The ARNO trial featured 850 patients who were randomized to bivalirudin (Angiomax) or UFH plus protamine. Patients in both arms had a mean age of about 69 years; 22% had diabetes.

Bivalirudin monotherapy was associated with significantly fewer in-hospital major bleeding events than was therapy with UFH and protamine (0.5% and 2.1%, respectively). At 1 month after the procedure, bivalirudin still was associated with significantly fewer major bleeding events (0.9% vs. 2.8%), Dr. David Antoniucci reported at Transcatheter Cardiovascular Therapeutic 2008.

The combined rate of MI, target vessel revascularization, and death at 1 month was significantly lower in bivalirudin-treated patients (2.8%) than in heparin-treated patients (6.4%), said Dr. Antoniucci of the cardiology division at Careggi Hospital, Florence, Italy.

The second trial presented was conducted to determine the safety of bivalirudin in diabetic patients undergoing PCI by Dr. Carlo Briguori and his coinvestigators in the interventional cardiology laboratory at Clinica Mediterranea, Naples, Italy. They randomized 335 diabetic patients with an average age of about 65 years to treatment with either bivalirudin alone or UFH plus tirofiban. Aspirin and clopidogrel (Plavix) were given before the procedure to all patients in the trial, called NAPLES (Novel Approaches for Preventing or Limiting Event Study). The severity of bleeding risk was distributed similarly in both groups of diabetic patients.

Despite having diabetes, only 13% of the patients had multivessel disease. Only 11%-19% of the patients had unstable angina. None had acute coronary syndrome with elevated biomarkers.

Bivalirudin was associated with a significantly lower rate of adverse clinical events than was UFH plus tirofiban (12% vs. 21%, respectively). The difference was due primarily to a significantly higher rate of bleeding of 8% in the combination therapy patients, compared with the 2% rate in bivalirudin-treated patients.

In both ARNO and NAPLES, patients received aspirin and clopidogrel before undergoing PCI. Bivalirudin was administered in a single 0.75-mg/kg IV bolus, followed by an infusion of 1.75 mg/kg per hour during PCI. Patients in the NAPLES trial received 70 U/kg UFH, followed by additional boluses if their activated clotting time was less than 250 seconds, whereas those in the ARNO trial initially received 100 U/kg UFH.

Both Dr. Antoniucci and Dr. Briguori reported having no financial conflicts of interest related to their studies.

WASHINGTON — The risk of adverse events such as major bleeding during elective coronary artery stenting is significantly lower when the procedure is performed with bivalirudin antithrombotic monotherapy than with other combinations based on unfractionated heparin, according to two Italian randomized trials.

The antithrombotic effects of bivalirudin have been shown to reduce bleeding rates after percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) alone, but few data exist that compare bivalirudin monotherapy with UFH in combination with a glycoprotein (GP) IIb/IIIa inhibitor such as tirofiban (Aggrastat) or with the heparin-reversing drug protamine.

One of bivalirudin's advantages over UFH is its short, 25-minute half-life. Investigators in the ARNO (Antithrombotic Regimens and Outcome) trial tried to see if this advantage could be equalized by administering protamine immediately after PCI to reverse the effects of UFH.

The ARNO trial featured 850 patients who were randomized to bivalirudin (Angiomax) or UFH plus protamine. Patients in both arms had a mean age of about 69 years; 22% had diabetes.

Bivalirudin monotherapy was associated with significantly fewer in-hospital major bleeding events than was therapy with UFH and protamine (0.5% and 2.1%, respectively). At 1 month after the procedure, bivalirudin still was associated with significantly fewer major bleeding events (0.9% vs. 2.8%), Dr. David Antoniucci reported at Transcatheter Cardiovascular Therapeutic 2008.

The combined rate of MI, target vessel revascularization, and death at 1 month was significantly lower in bivalirudin-treated patients (2.8%) than in heparin-treated patients (6.4%), said Dr. Antoniucci of the cardiology division at Careggi Hospital, Florence, Italy.

The second trial presented was conducted to determine the safety of bivalirudin in diabetic patients undergoing PCI by Dr. Carlo Briguori and his coinvestigators in the interventional cardiology laboratory at Clinica Mediterranea, Naples, Italy. They randomized 335 diabetic patients with an average age of about 65 years to treatment with either bivalirudin alone or UFH plus tirofiban. Aspirin and clopidogrel (Plavix) were given before the procedure to all patients in the trial, called NAPLES (Novel Approaches for Preventing or Limiting Event Study). The severity of bleeding risk was distributed similarly in both groups of diabetic patients.

Despite having diabetes, only 13% of the patients had multivessel disease. Only 11%-19% of the patients had unstable angina. None had acute coronary syndrome with elevated biomarkers.

Bivalirudin was associated with a significantly lower rate of adverse clinical events than was UFH plus tirofiban (12% vs. 21%, respectively). The difference was due primarily to a significantly higher rate of bleeding of 8% in the combination therapy patients, compared with the 2% rate in bivalirudin-treated patients.

In both ARNO and NAPLES, patients received aspirin and clopidogrel before undergoing PCI. Bivalirudin was administered in a single 0.75-mg/kg IV bolus, followed by an infusion of 1.75 mg/kg per hour during PCI. Patients in the NAPLES trial received 70 U/kg UFH, followed by additional boluses if their activated clotting time was less than 250 seconds, whereas those in the ARNO trial initially received 100 U/kg UFH.

Both Dr. Antoniucci and Dr. Briguori reported having no financial conflicts of interest related to their studies.

WASHINGTON — A prolonged infusion of bivalirudin during complex or multivessel percutaneous coronary interventions produced a significantly lower rate of procedure-related myocardial infarctions than did an intraprocedural infusion alone, without increasing the rate of major bleeding, in a small randomized trial of 178 patients with stable or unstable angina.

Previous studies have reported slightly higher rates of myocardial infarction or acute stent thrombosis in patients treated with bivalirudin, compared with patients who received heparin and a glycoprotein IIb/IIIa inhibitor, especially when there is an inadequate level of platelet inhibition provided by thienopyridines before the procedure, according to Dr. Bernardo Cortese of the department of interventional cardiology at the Ospedale della Misericordia, Grosseto, Italy.

In the PROBI VIRI study (Prolonged Bivalirudin Infusion Versus Intraprocedural Only Randomized Study), Dr. Cortese and his colleagues sought to determine if a prolonged infusion of bivalirudin for 4 hours after PCI (at 0.25 mg/kg per hour) could lower the rates of these events.

“We think that a prolonged infusion of bivalirudin in a specific subset of patients could be a reasonable choice to treat these patients with complex PCI and possibly emergent or urgent PCI to prevent stent thrombosis,” Dr. Cortese said at Transcatheter Cardiovascular Therapeutics 2008. Dr. Cortese is a consultant to Medicines Co., which manufactures bivalirudin.

To be randomized in the trial, patients were required to have stable or unstable angina and at least one complex lesion or a planned multivessel PCI.

The enrolled patients had a mean age of about 67 years; 40% had unstable angina, and 80% had a complex coronary lesion.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin than in those who received bivalirudin only during the procedure (6.8% and 16.7%, respectively). These MIs were defined by a rise in the level of CK-MB (the MB isoenzyme of creatine kinase) to three or more times the upper limit of normal.

Patients on prolonged bivalirudin achieved lower, yet statistically similar, rates of major adverse cardiac events at 30 days and 6 months (1.1% and 10.2%, respectively) than did patients who received bivalirudin only during the procedure (3.3% and 16.7%, respectively). Each group experienced similar rates of in-hospital bleeding described as major (about 1%) or minor (about 3%). No cases of stent thrombosis occurred.

The results raise the issue of “what should we do with stent thrombosis? Is it longer bivalirudin? Or is it more potent antiplatelet therapies? Those are the sort of pieces that this study doesn't answer, but at least it gives us a flavor of what might be considered,” Dr. E. Magnus Ohman, director of the program for advanced coronary disease at Duke University, Durham, N.C., commented after the study was presented.

“The issue may be not prolonging the infusion, but rather focusing on the platelet activation component where we actually know from some scientific areas that this may be our best approach.”

Dr. Cortese and Dr. Ohman both said that the conclusions that can be drawn from the study are limited by its small sample size and the use of radial access sites in more than 83% of the patients. Access sites in the radial artery have a much lower rate of bleeding than do those in the femoral artery. Significant reductions in bleeding events from femoral access sites have been a major part of the advantage ascribed to bivalirudin in other studies.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin. DR. CORTESE

WASHINGTON — A prolonged infusion of bivalirudin during complex or multivessel percutaneous coronary interventions produced a significantly lower rate of procedure-related myocardial infarctions than did an intraprocedural infusion alone, without increasing the rate of major bleeding, in a small randomized trial of 178 patients with stable or unstable angina.

Previous studies have reported slightly higher rates of myocardial infarction or acute stent thrombosis in patients treated with bivalirudin, compared with patients who received heparin and a glycoprotein IIb/IIIa inhibitor, especially when there is an inadequate level of platelet inhibition provided by thienopyridines before the procedure, according to Dr. Bernardo Cortese of the department of interventional cardiology at the Ospedale della Misericordia, Grosseto, Italy.

In the PROBI VIRI study (Prolonged Bivalirudin Infusion Versus Intraprocedural Only Randomized Study), Dr. Cortese and his colleagues sought to determine if a prolonged infusion of bivalirudin for 4 hours after PCI (at 0.25 mg/kg per hour) could lower the rates of these events.

“We think that a prolonged infusion of bivalirudin in a specific subset of patients could be a reasonable choice to treat these patients with complex PCI and possibly emergent or urgent PCI to prevent stent thrombosis,” Dr. Cortese said at Transcatheter Cardiovascular Therapeutics 2008. Dr. Cortese is a consultant to Medicines Co., which manufactures bivalirudin.

To be randomized in the trial, patients were required to have stable or unstable angina and at least one complex lesion or a planned multivessel PCI.

The enrolled patients had a mean age of about 67 years; 40% had unstable angina, and 80% had a complex coronary lesion.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin than in those who received bivalirudin only during the procedure (6.8% and 16.7%, respectively). These MIs were defined by a rise in the level of CK-MB (the MB isoenzyme of creatine kinase) to three or more times the upper limit of normal.

Patients on prolonged bivalirudin achieved lower, yet statistically similar, rates of major adverse cardiac events at 30 days and 6 months (1.1% and 10.2%, respectively) than did patients who received bivalirudin only during the procedure (3.3% and 16.7%, respectively). Each group experienced similar rates of in-hospital bleeding described as major (about 1%) or minor (about 3%). No cases of stent thrombosis occurred.

The results raise the issue of “what should we do with stent thrombosis? Is it longer bivalirudin? Or is it more potent antiplatelet therapies? Those are the sort of pieces that this study doesn't answer, but at least it gives us a flavor of what might be considered,” Dr. E. Magnus Ohman, director of the program for advanced coronary disease at Duke University, Durham, N.C., commented after the study was presented.

“The issue may be not prolonging the infusion, but rather focusing on the platelet activation component where we actually know from some scientific areas that this may be our best approach.”

Dr. Cortese and Dr. Ohman both said that the conclusions that can be drawn from the study are limited by its small sample size and the use of radial access sites in more than 83% of the patients. Access sites in the radial artery have a much lower rate of bleeding than do those in the femoral artery. Significant reductions in bleeding events from femoral access sites have been a major part of the advantage ascribed to bivalirudin in other studies.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin. DR. CORTESE

WASHINGTON — A prolonged infusion of bivalirudin during complex or multivessel percutaneous coronary interventions produced a significantly lower rate of procedure-related myocardial infarctions than did an intraprocedural infusion alone, without increasing the rate of major bleeding, in a small randomized trial of 178 patients with stable or unstable angina.

Previous studies have reported slightly higher rates of myocardial infarction or acute stent thrombosis in patients treated with bivalirudin, compared with patients who received heparin and a glycoprotein IIb/IIIa inhibitor, especially when there is an inadequate level of platelet inhibition provided by thienopyridines before the procedure, according to Dr. Bernardo Cortese of the department of interventional cardiology at the Ospedale della Misericordia, Grosseto, Italy.

In the PROBI VIRI study (Prolonged Bivalirudin Infusion Versus Intraprocedural Only Randomized Study), Dr. Cortese and his colleagues sought to determine if a prolonged infusion of bivalirudin for 4 hours after PCI (at 0.25 mg/kg per hour) could lower the rates of these events.

“We think that a prolonged infusion of bivalirudin in a specific subset of patients could be a reasonable choice to treat these patients with complex PCI and possibly emergent or urgent PCI to prevent stent thrombosis,” Dr. Cortese said at Transcatheter Cardiovascular Therapeutics 2008. Dr. Cortese is a consultant to Medicines Co., which manufactures bivalirudin.

To be randomized in the trial, patients were required to have stable or unstable angina and at least one complex lesion or a planned multivessel PCI.

The enrolled patients had a mean age of about 67 years; 40% had unstable angina, and 80% had a complex coronary lesion.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin than in those who received bivalirudin only during the procedure (6.8% and 16.7%, respectively). These MIs were defined by a rise in the level of CK-MB (the MB isoenzyme of creatine kinase) to three or more times the upper limit of normal.

Patients on prolonged bivalirudin achieved lower, yet statistically similar, rates of major adverse cardiac events at 30 days and 6 months (1.1% and 10.2%, respectively) than did patients who received bivalirudin only during the procedure (3.3% and 16.7%, respectively). Each group experienced similar rates of in-hospital bleeding described as major (about 1%) or minor (about 3%). No cases of stent thrombosis occurred.

The results raise the issue of “what should we do with stent thrombosis? Is it longer bivalirudin? Or is it more potent antiplatelet therapies? Those are the sort of pieces that this study doesn't answer, but at least it gives us a flavor of what might be considered,” Dr. E. Magnus Ohman, director of the program for advanced coronary disease at Duke University, Durham, N.C., commented after the study was presented.

“The issue may be not prolonging the infusion, but rather focusing on the platelet activation component where we actually know from some scientific areas that this may be our best approach.”

Dr. Cortese and Dr. Ohman both said that the conclusions that can be drawn from the study are limited by its small sample size and the use of radial access sites in more than 83% of the patients. Access sites in the radial artery have a much lower rate of bleeding than do those in the femoral artery. Significant reductions in bleeding events from femoral access sites have been a major part of the advantage ascribed to bivalirudin in other studies.

Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin. DR. CORTESE

WASHINGTON — Deployment of a proximal protection device during primary percutaneous coronary interventions for acute myocardial infarction may significantly increase the percentage of patients who immediately resolve ST-segment elevation, according to the results of a randomized trial.

The Proxis embolic protection system was not associated with any safety problems in the trial, called PREPARE (Proximal Embolic Protection in Acute MI and Resolution of ST-Elevation), which randomized 284 patients at two centers in the Netherlands and Canada. These patients had begun to experience ST-segment elevation myocardial infarction (STEMI) symptoms for 6 hours or less before their arrival at the hospital.

“It is well known that there is a good correlation between ST segment resolution and the results of percutaneous coronary intervention [PCI], in terms of myocardial salvage and long-term outcome,” said Dr. Karel T. Koch of the Academic Medical Center at the University of Amsterdam.

The device also has been used successfully for embolic protection in saphenous vein graft interventions, but the safety and effectiveness of the device for treating acute MI had not been reported prior to the PREPARE trial, except in a registry study of 172 patients (Rev. Cardiovasc. Med. 2007;8:160–6).

During a procedure with the Proxis system, an interventionalist places the system's flexible catheter in a position proximal to the target lesion and then uses CO₂ to inflate a sealing balloon on the tip of the catheter. This prevents antegrade flow during the intervention, after which stagnated blood and emboli are aspirated through the catheter.

In the PREPARE trial, complete ST-segment resolution (greater than 70%) was immediately apparent during PCI in a significantly greater percentage of patients who received protection with the Proxis system (86 [66%] of 129) than in control patients who went without embolic protection (67 [50%] of 135). But from 30 minutes out to 2 hours, there was no significant difference in ST-segment resolution between the groups, said Dr. Koch, who presented the results at Transcatheter Cardiovascular Therapeutics 2008.

Dr. Koch, the lead investigator of the trial, received research support from St. Jude Medical, which manufactures the Proxis system.

No differences could be found between the groups in the secondary end points of post-PCI, Thrombolysis in Mycardial Infarction-graded flow, myocardial blush grade, and angiographic signs of distal embolization.

The rates of another secondary end point, major adverse events at 30 days (composite of death, MI, target vessel revascularization, and stroke), were similar between Proxis-protected patients (4%) and control patients (7%). The trial was underpowered to detect any difference in this end point.

“If you have an early advantage, you can see an improvement in hard outcomes. This study was not big enough to look at that. But we do know from a large body of literature over the past 2 decades that earlier is better,” said Dr. David J. Cohen, director of cardiovascular research at St. Luke's Mid America Heart Institute, Kansas City, Mo.

Dr. Cohen reported receiving research support from Cordis Corp. and Boston Scientific Corp., both of which manufacture distal protection devices. He also is a consultant to Medtronic, which also produces a distal protection device.

At baseline, the patients had a mean age close to 60 years. Prior to randomization, all of the patients received 70 U/kg of unfractionated heparin, 300 mg of aspirin, and 600 mg of clopidogrel (Plavix). A core cardiac catheterization lab assessed the results without knowing the patients' treatment statuses.

The Proxis system was successfully placed in 94% of attempted patients. These patients underwent predilatation and stenting significantly more often than control patients (87% vs. 76%, respectively). They also underwent direct stenting significantly less often than control patients (11% vs. 19%). Close to 40% of patients in each group received platelet glycoprotein IIb/IIIa inhibitors. Thrombi were confirmed in 75% of patients who underwent percutaneous coronary intervention with the Proxis system.

The device was used nearly exclusively on totally occluded vessels, which makes it tough to assess the size of the clot, Dr. Cindy L. Grines, director of the cardiac catheterization laboratories at William Beaumont Hospital, Royal Oak, Mich., commented at the meeting. “If you don't know the clot size, you don't really know who needs distal embolic protection … because total occlusion can be due to a very large atherosclerotic burden and a tiny bit of clot, or it can be due to minimal plaque and a large clot. I would assume that these patients are going to react differently to proximal or distal protection devices.”

Dr. Grines also wondered whether “proximal protection can be applicable to less experienced centers,” especially given the fact that patients who received proximal protection had a median puncture to balloon time that was only 3 minutes longer than it was among control patients, at 17 and 14 minutes, respectively.

Dr. Grines disclosed that she serves on speakers bureaus for catheter-manufacturing companies, some of which make distal protection devices, and that she has consulted and received research funds from them.

Immediate STEMIresolution was significantly greater in patients who received proximal protection during PCI, said Dr. Karel T. Koch. Jeff Evans/Elsevier Global Medical News

WASHINGTON — Deployment of a proximal protection device during primary percutaneous coronary interventions for acute myocardial infarction may significantly increase the percentage of patients who immediately resolve ST-segment elevation, according to the results of a randomized trial.

The Proxis embolic protection system was not associated with any safety problems in the trial, called PREPARE (Proximal Embolic Protection in Acute MI and Resolution of ST-Elevation), which randomized 284 patients at two centers in the Netherlands and Canada. These patients had begun to experience ST-segment elevation myocardial infarction (STEMI) symptoms for 6 hours or less before their arrival at the hospital.

“It is well known that there is a good correlation between ST segment resolution and the results of percutaneous coronary intervention [PCI], in terms of myocardial salvage and long-term outcome,” said Dr. Karel T. Koch of the Academic Medical Center at the University of Amsterdam.

The device also has been used successfully for embolic protection in saphenous vein graft interventions, but the safety and effectiveness of the device for treating acute MI had not been reported prior to the PREPARE trial, except in a registry study of 172 patients (Rev. Cardiovasc. Med. 2007;8:160–6).

During a procedure with the Proxis system, an interventionalist places the system's flexible catheter in a position proximal to the target lesion and then uses CO₂ to inflate a sealing balloon on the tip of the catheter. This prevents antegrade flow during the intervention, after which stagnated blood and emboli are aspirated through the catheter.

In the PREPARE trial, complete ST-segment resolution (greater than 70%) was immediately apparent during PCI in a significantly greater percentage of patients who received protection with the Proxis system (86 [66%] of 129) than in control patients who went without embolic protection (67 [50%] of 135). But from 30 minutes out to 2 hours, there was no significant difference in ST-segment resolution between the groups, said Dr. Koch, who presented the results at Transcatheter Cardiovascular Therapeutics 2008.

Dr. Koch, the lead investigator of the trial, received research support from St. Jude Medical, which manufactures the Proxis system.

No differences could be found between the groups in the secondary end points of post-PCI, Thrombolysis in Mycardial Infarction-graded flow, myocardial blush grade, and angiographic signs of distal embolization.

The rates of another secondary end point, major adverse events at 30 days (composite of death, MI, target vessel revascularization, and stroke), were similar between Proxis-protected patients (4%) and control patients (7%). The trial was underpowered to detect any difference in this end point.

“If you have an early advantage, you can see an improvement in hard outcomes. This study was not big enough to look at that. But we do know from a large body of literature over the past 2 decades that earlier is better,” said Dr. David J. Cohen, director of cardiovascular research at St. Luke's Mid America Heart Institute, Kansas City, Mo.

Dr. Cohen reported receiving research support from Cordis Corp. and Boston Scientific Corp., both of which manufacture distal protection devices. He also is a consultant to Medtronic, which also produces a distal protection device.

At baseline, the patients had a mean age close to 60 years. Prior to randomization, all of the patients received 70 U/kg of unfractionated heparin, 300 mg of aspirin, and 600 mg of clopidogrel (Plavix). A core cardiac catheterization lab assessed the results without knowing the patients' treatment statuses.

The Proxis system was successfully placed in 94% of attempted patients. These patients underwent predilatation and stenting significantly more often than control patients (87% vs. 76%, respectively). They also underwent direct stenting significantly less often than control patients (11% vs. 19%). Close to 40% of patients in each group received platelet glycoprotein IIb/IIIa inhibitors. Thrombi were confirmed in 75% of patients who underwent percutaneous coronary intervention with the Proxis system.

The device was used nearly exclusively on totally occluded vessels, which makes it tough to assess the size of the clot, Dr. Cindy L. Grines, director of the cardiac catheterization laboratories at William Beaumont Hospital, Royal Oak, Mich., commented at the meeting. “If you don't know the clot size, you don't really know who needs distal embolic protection … because total occlusion can be due to a very large atherosclerotic burden and a tiny bit of clot, or it can be due to minimal plaque and a large clot. I would assume that these patients are going to react differently to proximal or distal protection devices.”

Dr. Grines also wondered whether “proximal protection can be applicable to less experienced centers,” especially given the fact that patients who received proximal protection had a median puncture to balloon time that was only 3 minutes longer than it was among control patients, at 17 and 14 minutes, respectively.

Dr. Grines disclosed that she serves on speakers bureaus for catheter-manufacturing companies, some of which make distal protection devices, and that she has consulted and received research funds from them.

Immediate STEMIresolution was significantly greater in patients who received proximal protection during PCI, said Dr. Karel T. Koch. Jeff Evans/Elsevier Global Medical News

WASHINGTON — Deployment of a proximal protection device during primary percutaneous coronary interventions for acute myocardial infarction may significantly increase the percentage of patients who immediately resolve ST-segment elevation, according to the results of a randomized trial.

The Proxis embolic protection system was not associated with any safety problems in the trial, called PREPARE (Proximal Embolic Protection in Acute MI and Resolution of ST-Elevation), which randomized 284 patients at two centers in the Netherlands and Canada. These patients had begun to experience ST-segment elevation myocardial infarction (STEMI) symptoms for 6 hours or less before their arrival at the hospital.

“It is well known that there is a good correlation between ST segment resolution and the results of percutaneous coronary intervention [PCI], in terms of myocardial salvage and long-term outcome,” said Dr. Karel T. Koch of the Academic Medical Center at the University of Amsterdam.

The device also has been used successfully for embolic protection in saphenous vein graft interventions, but the safety and effectiveness of the device for treating acute MI had not been reported prior to the PREPARE trial, except in a registry study of 172 patients (Rev. Cardiovasc. Med. 2007;8:160–6).

During a procedure with the Proxis system, an interventionalist places the system's flexible catheter in a position proximal to the target lesion and then uses CO₂ to inflate a sealing balloon on the tip of the catheter. This prevents antegrade flow during the intervention, after which stagnated blood and emboli are aspirated through the catheter.

In the PREPARE trial, complete ST-segment resolution (greater than 70%) was immediately apparent during PCI in a significantly greater percentage of patients who received protection with the Proxis system (86 [66%] of 129) than in control patients who went without embolic protection (67 [50%] of 135). But from 30 minutes out to 2 hours, there was no significant difference in ST-segment resolution between the groups, said Dr. Koch, who presented the results at Transcatheter Cardiovascular Therapeutics 2008.

Dr. Koch, the lead investigator of the trial, received research support from St. Jude Medical, which manufactures the Proxis system.

No differences could be found between the groups in the secondary end points of post-PCI, Thrombolysis in Mycardial Infarction-graded flow, myocardial blush grade, and angiographic signs of distal embolization.

The rates of another secondary end point, major adverse events at 30 days (composite of death, MI, target vessel revascularization, and stroke), were similar between Proxis-protected patients (4%) and control patients (7%). The trial was underpowered to detect any difference in this end point.

“If you have an early advantage, you can see an improvement in hard outcomes. This study was not big enough to look at that. But we do know from a large body of literature over the past 2 decades that earlier is better,” said Dr. David J. Cohen, director of cardiovascular research at St. Luke's Mid America Heart Institute, Kansas City, Mo.

Dr. Cohen reported receiving research support from Cordis Corp. and Boston Scientific Corp., both of which manufacture distal protection devices. He also is a consultant to Medtronic, which also produces a distal protection device.

At baseline, the patients had a mean age close to 60 years. Prior to randomization, all of the patients received 70 U/kg of unfractionated heparin, 300 mg of aspirin, and 600 mg of clopidogrel (Plavix). A core cardiac catheterization lab assessed the results without knowing the patients' treatment statuses.

The Proxis system was successfully placed in 94% of attempted patients. These patients underwent predilatation and stenting significantly more often than control patients (87% vs. 76%, respectively). They also underwent direct stenting significantly less often than control patients (11% vs. 19%). Close to 40% of patients in each group received platelet glycoprotein IIb/IIIa inhibitors. Thrombi were confirmed in 75% of patients who underwent percutaneous coronary intervention with the Proxis system.

The device was used nearly exclusively on totally occluded vessels, which makes it tough to assess the size of the clot, Dr. Cindy L. Grines, director of the cardiac catheterization laboratories at William Beaumont Hospital, Royal Oak, Mich., commented at the meeting. “If you don't know the clot size, you don't really know who needs distal embolic protection … because total occlusion can be due to a very large atherosclerotic burden and a tiny bit of clot, or it can be due to minimal plaque and a large clot. I would assume that these patients are going to react differently to proximal or distal protection devices.”

Dr. Grines also wondered whether “proximal protection can be applicable to less experienced centers,” especially given the fact that patients who received proximal protection had a median puncture to balloon time that was only 3 minutes longer than it was among control patients, at 17 and 14 minutes, respectively.

Dr. Grines disclosed that she serves on speakers bureaus for catheter-manufacturing companies, some of which make distal protection devices, and that she has consulted and received research funds from them.

Immediate STEMIresolution was significantly greater in patients who received proximal protection during PCI, said Dr. Karel T. Koch. Jeff Evans/Elsevier Global Medical News

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding when compared with heparin alone, according to a small randomized trial.

This increased bleeding rate—plus a lack of any added benefit with eptifibatide—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary in patients pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a ST-elevation MI (STEMI) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many U.S. centers, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% and 5.5%, respectively). At 6 months, the similarity persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%). However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

All of the patients in ASSIST (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

ASSIST was funded by Schering-Plough Canada Inc., which has exclusive U.S. marketing rights to eptifibatide, and Medtronic of Canada. Dr. Le May said that he and his associates initiated the trial independently of industry.

'Eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper.' DR. LE MAY

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding when compared with heparin alone, according to a small randomized trial.

This increased bleeding rate—plus a lack of any added benefit with eptifibatide—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary in patients pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a ST-elevation MI (STEMI) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many U.S. centers, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% and 5.5%, respectively). At 6 months, the similarity persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%). However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

All of the patients in ASSIST (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

ASSIST was funded by Schering-Plough Canada Inc., which has exclusive U.S. marketing rights to eptifibatide, and Medtronic of Canada. Dr. Le May said that he and his associates initiated the trial independently of industry.

'Eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper.' DR. LE MAY

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding when compared with heparin alone, according to a small randomized trial.

This increased bleeding rate—plus a lack of any added benefit with eptifibatide—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary in patients pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a ST-elevation MI (STEMI) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many U.S. centers, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% and 5.5%, respectively). At 6 months, the similarity persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%). However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

All of the patients in ASSIST (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

ASSIST was funded by Schering-Plough Canada Inc., which has exclusive U.S. marketing rights to eptifibatide, and Medtronic of Canada. Dr. Le May said that he and his associates initiated the trial independently of industry.

'Eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper.' DR. LE MAY

NATIONAL HARBOR, MD. — Vitamin D depletion in morbidly obese women who undergo laparoscopic Roux-en-Y gastric bypass can be resolved within about 3 months after starting weekly pharmacologic doses of the vitamin, according to the findings of a randomized trial.

Weekly oral dosing of 50,000 IU 25-hydroxyvitamin D also appeared to slow the rate of decline in bone mineral density (BMD) of the hip as well as increase the rate of hypertension resolution, Dr. Arthur M. Carlin reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Low levels of vitamin D have been implicated in the pathophysiology of hypertension, diabetes, cancer, osteoarthritis, and autoimmune diseases, Dr. Carlin said.

In one of several previous reports about vitamin D depletion in gastric bypass patients from Dr. Carlin and his coinvestigators at Henry Ford Hospital, Detroit, patients had a 60% prevalence of vitamin D depletion before surgery, based on serum concentrations of 20 ng/mL or less of 25-hydroxyvitamin D (Surg. Obes. Relat. Dis. 2006;2:98–103).

When the investigators began supplementing bariatric patients postoperatively with 1,500 mg calcium and 800 IU vitamin D, they saw a 20% rise in mean serum vitamin D levels from 20 to 24 ng/mL; the percentage of their patients with vitamin D depletion dropped from 53% to 44% (Surg. Obes. Relat. Dis. 2006;2:638–42).

During 2005–2006, Dr. Carlin and his colleagues randomized 60 morbidly obese women to either a weekly oral dose of 50,000 IU vitamin D or placebo. All of the patients received daily supplements of 1,500 mg calcium and 800 IU vitamin D.

After 1 year, weekly receipt of 50,000 IU vitamin D raised patients' mean serum vitamin D concentration to 38 ng/mL, which was significantly higher than a mean level of 15 ng/mL in placebo-treated patients. The patients reached the mean of 38 ng/mL after 3 months and it remained steady throughout the rest of the year.

Vitamin D depletion remained in significantly fewer of the patients who received the extra weekly dose, compared with those who received placebo (14% vs. 85%, respectively). Noncompliance accounted for continued vitamin D depletion in three patients who were supposed to take 50,000 IU each week.

Secondary hyperparathyroidism continued to occur in about 40% of patients in both groups. Bone turnover markers increased to similar levels in the groups.

After 1 year, patients who were treated weekly with 50,000 IU vitamin D lost significantly less BMD in the hip than did placebo-treated patients (8% vs. 12%, respectively), which suggests that vitamin D “attenuates this bone loss,” said Dr. Carlin, who reported no conflicts of interest.

A significantly greater proportion of hypertensive patients who received extra vitamin D resolved their hypertension than did those who received placebo (75% vs. 32%, respectively).

These results corroborate those from another study in which Dr. Carlin and his associates found that hypertension resolved in a significantly higher percentage of hypertensive patients with adequate vitamin D levels than in those with vitamin D depletion (61% vs. 42%) (Am. J. Surg. 2008;195:349–52).

In addition to giving daily calcium and vitamin D supplements to all gastric bypass patients, Dr. Carlin and his coinvestigators now recommend giving weekly 50,000 IU doses of vitamin D to patients with vitamin D depletion after gastric bypass.

In gastric bypass patients, poor mixing of bile salts at the Roux limb anastomosis leads to malabsorption of fat-soluble vitamins, such as vitamin D. This problem is compounded by the fact that the major site of vitamin D-dependent calcium absorption occurs in the duodenal proximal jejunal bypass. The body compensates for this resulting lack of calcium absorption by elevating levels of parathyroid hormone, which takes calcium from bones, Dr. Carlin said.

NATIONAL HARBOR, MD. — Vitamin D depletion in morbidly obese women who undergo laparoscopic Roux-en-Y gastric bypass can be resolved within about 3 months after starting weekly pharmacologic doses of the vitamin, according to the findings of a randomized trial.

Weekly oral dosing of 50,000 IU 25-hydroxyvitamin D also appeared to slow the rate of decline in bone mineral density (BMD) of the hip as well as increase the rate of hypertension resolution, Dr. Arthur M. Carlin reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Low levels of vitamin D have been implicated in the pathophysiology of hypertension, diabetes, cancer, osteoarthritis, and autoimmune diseases, Dr. Carlin said.

In one of several previous reports about vitamin D depletion in gastric bypass patients from Dr. Carlin and his coinvestigators at Henry Ford Hospital, Detroit, patients had a 60% prevalence of vitamin D depletion before surgery, based on serum concentrations of 20 ng/mL or less of 25-hydroxyvitamin D (Surg. Obes. Relat. Dis. 2006;2:98–103).

When the investigators began supplementing bariatric patients postoperatively with 1,500 mg calcium and 800 IU vitamin D, they saw a 20% rise in mean serum vitamin D levels from 20 to 24 ng/mL; the percentage of their patients with vitamin D depletion dropped from 53% to 44% (Surg. Obes. Relat. Dis. 2006;2:638–42).

During 2005–2006, Dr. Carlin and his colleagues randomized 60 morbidly obese women to either a weekly oral dose of 50,000 IU vitamin D or placebo. All of the patients received daily supplements of 1,500 mg calcium and 800 IU vitamin D.

After 1 year, weekly receipt of 50,000 IU vitamin D raised patients' mean serum vitamin D concentration to 38 ng/mL, which was significantly higher than a mean level of 15 ng/mL in placebo-treated patients. The patients reached the mean of 38 ng/mL after 3 months and it remained steady throughout the rest of the year.

Vitamin D depletion remained in significantly fewer of the patients who received the extra weekly dose, compared with those who received placebo (14% vs. 85%, respectively). Noncompliance accounted for continued vitamin D depletion in three patients who were supposed to take 50,000 IU each week.

Secondary hyperparathyroidism continued to occur in about 40% of patients in both groups. Bone turnover markers increased to similar levels in the groups.

After 1 year, patients who were treated weekly with 50,000 IU vitamin D lost significantly less BMD in the hip than did placebo-treated patients (8% vs. 12%, respectively), which suggests that vitamin D “attenuates this bone loss,” said Dr. Carlin, who reported no conflicts of interest.

A significantly greater proportion of hypertensive patients who received extra vitamin D resolved their hypertension than did those who received placebo (75% vs. 32%, respectively).

These results corroborate those from another study in which Dr. Carlin and his associates found that hypertension resolved in a significantly higher percentage of hypertensive patients with adequate vitamin D levels than in those with vitamin D depletion (61% vs. 42%) (Am. J. Surg. 2008;195:349–52).

In addition to giving daily calcium and vitamin D supplements to all gastric bypass patients, Dr. Carlin and his coinvestigators now recommend giving weekly 50,000 IU doses of vitamin D to patients with vitamin D depletion after gastric bypass.

In gastric bypass patients, poor mixing of bile salts at the Roux limb anastomosis leads to malabsorption of fat-soluble vitamins, such as vitamin D. This problem is compounded by the fact that the major site of vitamin D-dependent calcium absorption occurs in the duodenal proximal jejunal bypass. The body compensates for this resulting lack of calcium absorption by elevating levels of parathyroid hormone, which takes calcium from bones, Dr. Carlin said.

NATIONAL HARBOR, MD. — Vitamin D depletion in morbidly obese women who undergo laparoscopic Roux-en-Y gastric bypass can be resolved within about 3 months after starting weekly pharmacologic doses of the vitamin, according to the findings of a randomized trial.

Weekly oral dosing of 50,000 IU 25-hydroxyvitamin D also appeared to slow the rate of decline in bone mineral density (BMD) of the hip as well as increase the rate of hypertension resolution, Dr. Arthur M. Carlin reported at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Low levels of vitamin D have been implicated in the pathophysiology of hypertension, diabetes, cancer, osteoarthritis, and autoimmune diseases, Dr. Carlin said.

In one of several previous reports about vitamin D depletion in gastric bypass patients from Dr. Carlin and his coinvestigators at Henry Ford Hospital, Detroit, patients had a 60% prevalence of vitamin D depletion before surgery, based on serum concentrations of 20 ng/mL or less of 25-hydroxyvitamin D (Surg. Obes. Relat. Dis. 2006;2:98–103).

When the investigators began supplementing bariatric patients postoperatively with 1,500 mg calcium and 800 IU vitamin D, they saw a 20% rise in mean serum vitamin D levels from 20 to 24 ng/mL; the percentage of their patients with vitamin D depletion dropped from 53% to 44% (Surg. Obes. Relat. Dis. 2006;2:638–42).

During 2005–2006, Dr. Carlin and his colleagues randomized 60 morbidly obese women to either a weekly oral dose of 50,000 IU vitamin D or placebo. All of the patients received daily supplements of 1,500 mg calcium and 800 IU vitamin D.

After 1 year, weekly receipt of 50,000 IU vitamin D raised patients' mean serum vitamin D concentration to 38 ng/mL, which was significantly higher than a mean level of 15 ng/mL in placebo-treated patients. The patients reached the mean of 38 ng/mL after 3 months and it remained steady throughout the rest of the year.

Vitamin D depletion remained in significantly fewer of the patients who received the extra weekly dose, compared with those who received placebo (14% vs. 85%, respectively). Noncompliance accounted for continued vitamin D depletion in three patients who were supposed to take 50,000 IU each week.

Secondary hyperparathyroidism continued to occur in about 40% of patients in both groups. Bone turnover markers increased to similar levels in the groups.

After 1 year, patients who were treated weekly with 50,000 IU vitamin D lost significantly less BMD in the hip than did placebo-treated patients (8% vs. 12%, respectively), which suggests that vitamin D “attenuates this bone loss,” said Dr. Carlin, who reported no conflicts of interest.

A significantly greater proportion of hypertensive patients who received extra vitamin D resolved their hypertension than did those who received placebo (75% vs. 32%, respectively).

These results corroborate those from another study in which Dr. Carlin and his associates found that hypertension resolved in a significantly higher percentage of hypertensive patients with adequate vitamin D levels than in those with vitamin D depletion (61% vs. 42%) (Am. J. Surg. 2008;195:349–52).

In addition to giving daily calcium and vitamin D supplements to all gastric bypass patients, Dr. Carlin and his coinvestigators now recommend giving weekly 50,000 IU doses of vitamin D to patients with vitamin D depletion after gastric bypass.

In gastric bypass patients, poor mixing of bile salts at the Roux limb anastomosis leads to malabsorption of fat-soluble vitamins, such as vitamin D. This problem is compounded by the fact that the major site of vitamin D-dependent calcium absorption occurs in the duodenal proximal jejunal bypass. The body compensates for this resulting lack of calcium absorption by elevating levels of parathyroid hormone, which takes calcium from bones, Dr. Carlin said.