Kerri Wachter

Major Finding: Conventional risk factors accounted for 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, George Howard, Dr.P.H., reported at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence in blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It is estimated that stroke mortality is 40% greater in blacks than in whites, he noted. “These are massive differences in mortality.”

Study participants have been selected from a commercially available list and were recruited by mail and telephone. The researchers use a computer-assisted telephone interview that includes cardiovascular disease history. This is followed by a home visit for venipuncture, ECG, and physical measures.

Participants are followed at 6-month intervals for stroke surveillance. Suspected events are adjudicated centrally. Currently, there are 352 events among 26,610 participants, who were stroke and/or TIA free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk in blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence in blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard said.

Major Finding: Conventional risk factors accounted for 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, George Howard, Dr.P.H., reported at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence in blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It is estimated that stroke mortality is 40% greater in blacks than in whites, he noted. “These are massive differences in mortality.”

Study participants have been selected from a commercially available list and were recruited by mail and telephone. The researchers use a computer-assisted telephone interview that includes cardiovascular disease history. This is followed by a home visit for venipuncture, ECG, and physical measures.

Participants are followed at 6-month intervals for stroke surveillance. Suspected events are adjudicated centrally. Currently, there are 352 events among 26,610 participants, who were stroke and/or TIA free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk in blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence in blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard said.

Major Finding: Conventional risk factors accounted for 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, George Howard, Dr.P.H., reported at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence in blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It is estimated that stroke mortality is 40% greater in blacks than in whites, he noted. “These are massive differences in mortality.”

Study participants have been selected from a commercially available list and were recruited by mail and telephone. The researchers use a computer-assisted telephone interview that includes cardiovascular disease history. This is followed by a home visit for venipuncture, ECG, and physical measures.

Participants are followed at 6-month intervals for stroke surveillance. Suspected events are adjudicated centrally. Currently, there are 352 events among 26,610 participants, who were stroke and/or TIA free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk in blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence in blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard said.

WASHINGTON — Tamoxifen and raloxifene offer women at high risk of developing breast cancer two effective options to prevent the disease, based on 8 years of follow-up data for more than 19,000 women in the STAR trial.

While tamoxifen proved significantly more effective in preventing invasive breast cancer, there was no significant difference between the two drugs in preventing noninvasive breast cancer. And raloxifene (Evista) had significantly less toxicity, including endometrial cancer, thromboembolic complications, and cataracts.

“These data are good news for postmenopausal women who want to reduce their risk of breast cancer,” said Dr. D. Lawrence Wickerham, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP). “The important message is that both [drugs] are options. The decision is a shared one between the patient and her physician.”

Dr. Wickerham presented the latest results for the Study of Tamoxifen and Raloxifene (STAR) trial during a late-breaker session at the annual meeting of the American Association for Cancer Research. The results were also published in the journal Cancer Prevention Research (April 19, 2010; doi: 10.1158/1940-6207.CAPR-10-0076).

Oncologists at the meeting expressed frustration that more women at high risk are not on the drugs, given the proven efficacy of the two selective estrogen receptor modulators (SERMs) in preventing breast cancer.

“I have to ask, why aren't the results of the BCPT [breast cancer prevention trial] and STAR trials more vigorously applied in clinical practice?” said Dr. Gabriel N. Hortobagyi, who was the discussant.

Dr. Wickerham echoed this frustration during a press conference. “I see women each week, at a high risk of breast cancer, and I will end up telling one or two of them… all too often…that they have breast cancer. I'd love for that part of my job to go away. These data are a step in that direction” said Dr. Wickerham, chief of the cancer genetics and prevention section at Allegheny General Hospital in Pittsburgh. The randomized, double-blind federally funded STAR trial included women at least 35 years of age with a 5-year predicted breast cancer risk of at least 1.66% (based on a modified version of the Gail model). Researchers from the NSABP randomized 19, 747 women to receive either tamoxifen or raloxifene (JAMA 2006;295:2742-51).

The update includes 19,490 women—9,736 on tamoxifen and 9,754 on raloxifene. The differences in numbers are due to a combination of loss during follow-up or follow-up data becoming available for women who were lost to follow-up in the original report. Women on tamoxifen received 20 mg/day and those on raloxifene received 60 mg/day.

At an average follow-up of 8 years, the relative risk of invasive breast cancer on raloxifene, compared with tamoxifen was 1.24, which was significant (P = .01). Both drugs reduced the risk of invasive breast cancer by roughly 50% in the original report (median follow-up 47 months).

“We have estimated, however, that this difference in the raloxifene-treated group represents 76% of tamoxifen's chemopreventative benefit, which translates into at 38% reduction in invasive breast cancers,” Dr. Wickerham said.

In the 2006 report, raloxifene (81 events) did not appear to be as effective as tamoxifen (57 events) in preventing noninvasive breast cancer (P = .052). “Now with additional follow-up, those differences have narrowed,” he said. At 8 years, there was no statistical significance between the two groups with a risk ratio of 1.22 (P = .12). The relative risk of 1.22 favors tamoxifen, but raloxifene preserves 78% of the chemopreventative benefit of tamoxifen. This translates to raloxifene preventing 39% of noninvasive breast cancers.

Raloxifene maintained its toxicity advantage. The relative risk of uterine cancers with raloxifene vs. tamoxifen was 0.55. There also were twice as many hysterectomies for benign disease in the tamoxifen group. This was due in part to an 80% increase in hyperplasia of the endometrium that occurred in women on tamoxifen, Dr. Wickerham said.

Both drugs increase the risk of thromboembolic complications, but there were significantly fewer (P = .007) of these events in women on raloxifene (154), compared with tamoxifen (202).

Dr. Hortobagyi, director of the breast cancer research program at the University of Texas M.D. Anderson Cancer Center in Houston, identified factors that may be responsible for limited use of tamoxifen and raloxifene for prevention. He cited misinformation about the drugs, fears about toxicities, limited high-risk prediction tools, lack of a marker or measurement to monitor for risk reduction, cost, and insufficient public and professional education about the drugs.

“There is no perfect drug. Certainly in other areas of preventive medicine, there seems to be greater tolerance for adverse effects for effective preventative interventions,” he said, noting discrepancy between what is considered acceptable risk for other preventative drugs and SERMs. For example, drugs used to prevent hypertension and coronary artery disease have more and more serious adverse events than SERMs, he said.

“The challenge today is how to communicate to the public to enhance the utilization of SERMs and reduce further the incidence of breast cancer,” he said.

Disclosures: The study was supported by the National Cancer Institute. Dr. Wickerham reported that he has consulted for Eli Lilly.

'These data are good news for postmenopausal women who want to reduce their risk of breast cancer.'

Source DR. WICKERHAM

'The challenge today is how to communicate to the public to enhance the utilization of SERMs.'

Source DR. HORTOBAGYI

WASHINGTON — Tamoxifen and raloxifene offer women at high risk of developing breast cancer two effective options to prevent the disease, based on 8 years of follow-up data for more than 19,000 women in the STAR trial.

While tamoxifen proved significantly more effective in preventing invasive breast cancer, there was no significant difference between the two drugs in preventing noninvasive breast cancer. And raloxifene (Evista) had significantly less toxicity, including endometrial cancer, thromboembolic complications, and cataracts.

“These data are good news for postmenopausal women who want to reduce their risk of breast cancer,” said Dr. D. Lawrence Wickerham, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP). “The important message is that both [drugs] are options. The decision is a shared one between the patient and her physician.”

Dr. Wickerham presented the latest results for the Study of Tamoxifen and Raloxifene (STAR) trial during a late-breaker session at the annual meeting of the American Association for Cancer Research. The results were also published in the journal Cancer Prevention Research (April 19, 2010; doi: 10.1158/1940-6207.CAPR-10-0076).

Oncologists at the meeting expressed frustration that more women at high risk are not on the drugs, given the proven efficacy of the two selective estrogen receptor modulators (SERMs) in preventing breast cancer.

“I have to ask, why aren't the results of the BCPT [breast cancer prevention trial] and STAR trials more vigorously applied in clinical practice?” said Dr. Gabriel N. Hortobagyi, who was the discussant.

Dr. Wickerham echoed this frustration during a press conference. “I see women each week, at a high risk of breast cancer, and I will end up telling one or two of them… all too often…that they have breast cancer. I'd love for that part of my job to go away. These data are a step in that direction” said Dr. Wickerham, chief of the cancer genetics and prevention section at Allegheny General Hospital in Pittsburgh. The randomized, double-blind federally funded STAR trial included women at least 35 years of age with a 5-year predicted breast cancer risk of at least 1.66% (based on a modified version of the Gail model). Researchers from the NSABP randomized 19, 747 women to receive either tamoxifen or raloxifene (JAMA 2006;295:2742-51).

The update includes 19,490 women—9,736 on tamoxifen and 9,754 on raloxifene. The differences in numbers are due to a combination of loss during follow-up or follow-up data becoming available for women who were lost to follow-up in the original report. Women on tamoxifen received 20 mg/day and those on raloxifene received 60 mg/day.

At an average follow-up of 8 years, the relative risk of invasive breast cancer on raloxifene, compared with tamoxifen was 1.24, which was significant (P = .01). Both drugs reduced the risk of invasive breast cancer by roughly 50% in the original report (median follow-up 47 months).

“We have estimated, however, that this difference in the raloxifene-treated group represents 76% of tamoxifen's chemopreventative benefit, which translates into at 38% reduction in invasive breast cancers,” Dr. Wickerham said.

In the 2006 report, raloxifene (81 events) did not appear to be as effective as tamoxifen (57 events) in preventing noninvasive breast cancer (P = .052). “Now with additional follow-up, those differences have narrowed,” he said. At 8 years, there was no statistical significance between the two groups with a risk ratio of 1.22 (P = .12). The relative risk of 1.22 favors tamoxifen, but raloxifene preserves 78% of the chemopreventative benefit of tamoxifen. This translates to raloxifene preventing 39% of noninvasive breast cancers.

Raloxifene maintained its toxicity advantage. The relative risk of uterine cancers with raloxifene vs. tamoxifen was 0.55. There also were twice as many hysterectomies for benign disease in the tamoxifen group. This was due in part to an 80% increase in hyperplasia of the endometrium that occurred in women on tamoxifen, Dr. Wickerham said.

Both drugs increase the risk of thromboembolic complications, but there were significantly fewer (P = .007) of these events in women on raloxifene (154), compared with tamoxifen (202).

Dr. Hortobagyi, director of the breast cancer research program at the University of Texas M.D. Anderson Cancer Center in Houston, identified factors that may be responsible for limited use of tamoxifen and raloxifene for prevention. He cited misinformation about the drugs, fears about toxicities, limited high-risk prediction tools, lack of a marker or measurement to monitor for risk reduction, cost, and insufficient public and professional education about the drugs.

“There is no perfect drug. Certainly in other areas of preventive medicine, there seems to be greater tolerance for adverse effects for effective preventative interventions,” he said, noting discrepancy between what is considered acceptable risk for other preventative drugs and SERMs. For example, drugs used to prevent hypertension and coronary artery disease have more and more serious adverse events than SERMs, he said.

“The challenge today is how to communicate to the public to enhance the utilization of SERMs and reduce further the incidence of breast cancer,” he said.

Disclosures: The study was supported by the National Cancer Institute. Dr. Wickerham reported that he has consulted for Eli Lilly.

'These data are good news for postmenopausal women who want to reduce their risk of breast cancer.'

Source DR. WICKERHAM

'The challenge today is how to communicate to the public to enhance the utilization of SERMs.'

Source DR. HORTOBAGYI

WASHINGTON — Tamoxifen and raloxifene offer women at high risk of developing breast cancer two effective options to prevent the disease, based on 8 years of follow-up data for more than 19,000 women in the STAR trial.

While tamoxifen proved significantly more effective in preventing invasive breast cancer, there was no significant difference between the two drugs in preventing noninvasive breast cancer. And raloxifene (Evista) had significantly less toxicity, including endometrial cancer, thromboembolic complications, and cataracts.

“These data are good news for postmenopausal women who want to reduce their risk of breast cancer,” said Dr. D. Lawrence Wickerham, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP). “The important message is that both [drugs] are options. The decision is a shared one between the patient and her physician.”

Dr. Wickerham presented the latest results for the Study of Tamoxifen and Raloxifene (STAR) trial during a late-breaker session at the annual meeting of the American Association for Cancer Research. The results were also published in the journal Cancer Prevention Research (April 19, 2010; doi: 10.1158/1940-6207.CAPR-10-0076).

Oncologists at the meeting expressed frustration that more women at high risk are not on the drugs, given the proven efficacy of the two selective estrogen receptor modulators (SERMs) in preventing breast cancer.

“I have to ask, why aren't the results of the BCPT [breast cancer prevention trial] and STAR trials more vigorously applied in clinical practice?” said Dr. Gabriel N. Hortobagyi, who was the discussant.

Dr. Wickerham echoed this frustration during a press conference. “I see women each week, at a high risk of breast cancer, and I will end up telling one or two of them… all too often…that they have breast cancer. I'd love for that part of my job to go away. These data are a step in that direction” said Dr. Wickerham, chief of the cancer genetics and prevention section at Allegheny General Hospital in Pittsburgh. The randomized, double-blind federally funded STAR trial included women at least 35 years of age with a 5-year predicted breast cancer risk of at least 1.66% (based on a modified version of the Gail model). Researchers from the NSABP randomized 19, 747 women to receive either tamoxifen or raloxifene (JAMA 2006;295:2742-51).

The update includes 19,490 women—9,736 on tamoxifen and 9,754 on raloxifene. The differences in numbers are due to a combination of loss during follow-up or follow-up data becoming available for women who were lost to follow-up in the original report. Women on tamoxifen received 20 mg/day and those on raloxifene received 60 mg/day.

At an average follow-up of 8 years, the relative risk of invasive breast cancer on raloxifene, compared with tamoxifen was 1.24, which was significant (P = .01). Both drugs reduced the risk of invasive breast cancer by roughly 50% in the original report (median follow-up 47 months).

“We have estimated, however, that this difference in the raloxifene-treated group represents 76% of tamoxifen's chemopreventative benefit, which translates into at 38% reduction in invasive breast cancers,” Dr. Wickerham said.

In the 2006 report, raloxifene (81 events) did not appear to be as effective as tamoxifen (57 events) in preventing noninvasive breast cancer (P = .052). “Now with additional follow-up, those differences have narrowed,” he said. At 8 years, there was no statistical significance between the two groups with a risk ratio of 1.22 (P = .12). The relative risk of 1.22 favors tamoxifen, but raloxifene preserves 78% of the chemopreventative benefit of tamoxifen. This translates to raloxifene preventing 39% of noninvasive breast cancers.

Raloxifene maintained its toxicity advantage. The relative risk of uterine cancers with raloxifene vs. tamoxifen was 0.55. There also were twice as many hysterectomies for benign disease in the tamoxifen group. This was due in part to an 80% increase in hyperplasia of the endometrium that occurred in women on tamoxifen, Dr. Wickerham said.

Both drugs increase the risk of thromboembolic complications, but there were significantly fewer (P = .007) of these events in women on raloxifene (154), compared with tamoxifen (202).

Dr. Hortobagyi, director of the breast cancer research program at the University of Texas M.D. Anderson Cancer Center in Houston, identified factors that may be responsible for limited use of tamoxifen and raloxifene for prevention. He cited misinformation about the drugs, fears about toxicities, limited high-risk prediction tools, lack of a marker or measurement to monitor for risk reduction, cost, and insufficient public and professional education about the drugs.

“There is no perfect drug. Certainly in other areas of preventive medicine, there seems to be greater tolerance for adverse effects for effective preventative interventions,” he said, noting discrepancy between what is considered acceptable risk for other preventative drugs and SERMs. For example, drugs used to prevent hypertension and coronary artery disease have more and more serious adverse events than SERMs, he said.

“The challenge today is how to communicate to the public to enhance the utilization of SERMs and reduce further the incidence of breast cancer,” he said.

Disclosures: The study was supported by the National Cancer Institute. Dr. Wickerham reported that he has consulted for Eli Lilly.

'These data are good news for postmenopausal women who want to reduce their risk of breast cancer.'

Source DR. WICKERHAM

'The challenge today is how to communicate to the public to enhance the utilization of SERMs.'

Source DR. HORTOBAGYI

Major Finding: 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection are estimated to have occurred worldwide in children younger than 5 years in 2005. Mortality related to the infection was estimated to be 66,000-199,000.

Data Source: Systematic review of 36 incidence studies, including 10 unpublished studies.

Disclosures: The World Health Organization and Bill & Melinda Gates Foundation funded the study.

An estimated 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection occurred worldwide in children younger than 5 years of age in 2005, based on results of the first study to take a global view of this deadly infection.

The systematic review and meta-analysis used published and unpublished incidence and mortality data for respiratory syncytial virus (RSV)–associated acute lower respiratory infection (ALRI) in both industrialized and developing countries.

The researchers estimated that, worldwide, 3.4 million young children developed RSV-associated severe ALRI necessitating hospital admission and 66,000-199,000 children younger than 5 years of age died from the infection. A total of 99% of these deaths occurred in developing countries, reported Dr. Harish Nair and his coauthors (Lancet April 16 [doi:10.1016/S0140-6736(10)60206-1]).

The authors pointed out that “substantial uncertainty surrounds case fatality ratio estimates from developing countries. To that end, the researchers calculated three estimates of RSV-associated ALRI fatalities to assess the upper and lower bounds, yielding the 66,000-199,000 range.

The incidence of RSV-associated ALRI in developing nations was twice that for industrialized nations. “This estimate represents roughly 22% of all episodes of ALRI in young children,” wrote Dr. Nair, a public health sciences doctoral student at the University of Edinburgh, and colleagues.

In an accompanying commentary, Dr. Caroline Breese Hall, professor of pediatrics and infectious diseases at the University of Rochester (N.Y.), highlighted the importance of the study. The researchers “provide the best current estimates of the global under-5 burden of RSV-associated acute lower respiratory tract infections, and convincingly posit the virus as the foremost cause of all lower respiratory-tract infections in young children worldwide” (Lancet April 16 [doi:10.1016/S0140-6736(10)60401-1]).

The researchers started by performing a systematic literature review using a combination of search terms, manual searching of online journals, and scanning reference lists of identified citations. Studies were limited to those from January 1995 to June 2009. In addition, the researchers “invited the participation of researchers who had done similar studies resulting in unpublished data or supplementary data from published work.”

As inclusion criteria, the researchers chose to use ALRI and severe ALRI, including bronchiolitis and pneumonia. ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall with fast breathing for age. Severe ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall (with or without fast breathing for age) that required hospitalization.

Dr. Nair and his associates identified 36 studies with suitable data: 19 published population-based studies, 7 published studies based on hospital discharge records and laboratory diagnosis reports, and 10 unpublished population-based studies. The researchers noted that few studies reported data for the full age range (0-5 years).

Dr. Nair reported that he has no relevant financial relationships, but several of his coauthors reported receiving grant funding and/or honoraria from various vaccine manufacturers. Dr. Hall reported that she has received consultation fees and grant support from MedImmune Inc.

Major Finding: 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection are estimated to have occurred worldwide in children younger than 5 years in 2005. Mortality related to the infection was estimated to be 66,000-199,000.

Data Source: Systematic review of 36 incidence studies, including 10 unpublished studies.

Disclosures: The World Health Organization and Bill & Melinda Gates Foundation funded the study.

An estimated 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection occurred worldwide in children younger than 5 years of age in 2005, based on results of the first study to take a global view of this deadly infection.

The systematic review and meta-analysis used published and unpublished incidence and mortality data for respiratory syncytial virus (RSV)–associated acute lower respiratory infection (ALRI) in both industrialized and developing countries.

The researchers estimated that, worldwide, 3.4 million young children developed RSV-associated severe ALRI necessitating hospital admission and 66,000-199,000 children younger than 5 years of age died from the infection. A total of 99% of these deaths occurred in developing countries, reported Dr. Harish Nair and his coauthors (Lancet April 16 [doi:10.1016/S0140-6736(10)60206-1]).

The authors pointed out that “substantial uncertainty surrounds case fatality ratio estimates from developing countries. To that end, the researchers calculated three estimates of RSV-associated ALRI fatalities to assess the upper and lower bounds, yielding the 66,000-199,000 range.

The incidence of RSV-associated ALRI in developing nations was twice that for industrialized nations. “This estimate represents roughly 22% of all episodes of ALRI in young children,” wrote Dr. Nair, a public health sciences doctoral student at the University of Edinburgh, and colleagues.

In an accompanying commentary, Dr. Caroline Breese Hall, professor of pediatrics and infectious diseases at the University of Rochester (N.Y.), highlighted the importance of the study. The researchers “provide the best current estimates of the global under-5 burden of RSV-associated acute lower respiratory tract infections, and convincingly posit the virus as the foremost cause of all lower respiratory-tract infections in young children worldwide” (Lancet April 16 [doi:10.1016/S0140-6736(10)60401-1]).

The researchers started by performing a systematic literature review using a combination of search terms, manual searching of online journals, and scanning reference lists of identified citations. Studies were limited to those from January 1995 to June 2009. In addition, the researchers “invited the participation of researchers who had done similar studies resulting in unpublished data or supplementary data from published work.”

As inclusion criteria, the researchers chose to use ALRI and severe ALRI, including bronchiolitis and pneumonia. ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall with fast breathing for age. Severe ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall (with or without fast breathing for age) that required hospitalization.

Dr. Nair and his associates identified 36 studies with suitable data: 19 published population-based studies, 7 published studies based on hospital discharge records and laboratory diagnosis reports, and 10 unpublished population-based studies. The researchers noted that few studies reported data for the full age range (0-5 years).

Dr. Nair reported that he has no relevant financial relationships, but several of his coauthors reported receiving grant funding and/or honoraria from various vaccine manufacturers. Dr. Hall reported that she has received consultation fees and grant support from MedImmune Inc.

Major Finding: 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection are estimated to have occurred worldwide in children younger than 5 years in 2005. Mortality related to the infection was estimated to be 66,000-199,000.

Data Source: Systematic review of 36 incidence studies, including 10 unpublished studies.

Disclosures: The World Health Organization and Bill & Melinda Gates Foundation funded the study.

An estimated 33.8 million new episodes of respiratory syncytial virus–associated acute lower respiratory infection occurred worldwide in children younger than 5 years of age in 2005, based on results of the first study to take a global view of this deadly infection.

The systematic review and meta-analysis used published and unpublished incidence and mortality data for respiratory syncytial virus (RSV)–associated acute lower respiratory infection (ALRI) in both industrialized and developing countries.

The researchers estimated that, worldwide, 3.4 million young children developed RSV-associated severe ALRI necessitating hospital admission and 66,000-199,000 children younger than 5 years of age died from the infection. A total of 99% of these deaths occurred in developing countries, reported Dr. Harish Nair and his coauthors (Lancet April 16 [doi:10.1016/S0140-6736(10)60206-1]).

The authors pointed out that “substantial uncertainty surrounds case fatality ratio estimates from developing countries. To that end, the researchers calculated three estimates of RSV-associated ALRI fatalities to assess the upper and lower bounds, yielding the 66,000-199,000 range.

The incidence of RSV-associated ALRI in developing nations was twice that for industrialized nations. “This estimate represents roughly 22% of all episodes of ALRI in young children,” wrote Dr. Nair, a public health sciences doctoral student at the University of Edinburgh, and colleagues.

In an accompanying commentary, Dr. Caroline Breese Hall, professor of pediatrics and infectious diseases at the University of Rochester (N.Y.), highlighted the importance of the study. The researchers “provide the best current estimates of the global under-5 burden of RSV-associated acute lower respiratory tract infections, and convincingly posit the virus as the foremost cause of all lower respiratory-tract infections in young children worldwide” (Lancet April 16 [doi:10.1016/S0140-6736(10)60401-1]).

The researchers started by performing a systematic literature review using a combination of search terms, manual searching of online journals, and scanning reference lists of identified citations. Studies were limited to those from January 1995 to June 2009. In addition, the researchers “invited the participation of researchers who had done similar studies resulting in unpublished data or supplementary data from published work.”

As inclusion criteria, the researchers chose to use ALRI and severe ALRI, including bronchiolitis and pneumonia. ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall with fast breathing for age. Severe ALRI was considered the presence of cough or difficulty breathing with indrawing of the lower chest wall (with or without fast breathing for age) that required hospitalization.

Dr. Nair and his associates identified 36 studies with suitable data: 19 published population-based studies, 7 published studies based on hospital discharge records and laboratory diagnosis reports, and 10 unpublished population-based studies. The researchers noted that few studies reported data for the full age range (0-5 years).

Dr. Nair reported that he has no relevant financial relationships, but several of his coauthors reported receiving grant funding and/or honoraria from various vaccine manufacturers. Dr. Hall reported that she has received consultation fees and grant support from MedImmune Inc.

Major Finding: 11.3% of individuals classified as low risk and 12.8% of individuals classified as intermediate risk using the Framingham Risk Score had an abnormal ankle brachial index.

Data Source: A multicenter cross-sectional study of 822 individuals conducted in conjunction with a national free public PAD screening program conducted at 23 sites during 2007-2009.

Disclosures: Dr. Dhanghana reported that he has no relevant financial relationships.

TAMPA — More than 10% of patients with low to intermediate risk for coronary heart disease have an abnormal ankle brachial index, putting them at a higher risk for myocardial infarction and coronary death than predicted by conventional measures.

In a study of 822 individuals screened for peripheral artery disease (PAD), 11% of those with a low-risk Framingham Risk Score (FRS) for coronary disease and 13% of those with an intermediate-risk score had an abnormal ankle brachial index (ABI).

Abnormal ABI has been associated with increased risk of coronary heart disease events and mortality, even in individuals at low to intermediate CHD risk (JAMA 2008;300:197-208).

However, prevalence estimates of abnormal ABI among older screening populations with low-intermediate FRS have not been reported previously, Dr. Raj Dhangana said at the annual meeting of the Society of Interventional Radiology.

“The prevalence of abnormal ABI is high, even in those a without high Framingham Risk Score. … The use of abnormal ABI in screening has the potential to improve risk prediction,” according to Dr. Dhangana.

The findings are good news, given that at least 60% of CHD events occur in individuals who were not known to be at high risk (BMJ 2003;327:1267). In fact, almost two-thirds of events occur in individuals who are either at low or intermediate risk using the FRS (Am. Heart J. 2002;144:95-100).

The use of ABI for screening could help improve risk prediction for CHD, said Dr. Dhangana, a research fellow at Rhode Island Hospital in Providence.

The researchers analyzed data from the PEDAL Study (Population-Based Examinations to Determine Ankle-Brachial Index)—a multicenter, cross-sectional study conducted at 23 sites of the Legs for Life national free public PAD screening program in 2007-2009.

Patients were included in the analysis if they were at least age 18 years and if their ABI and FRS variables were available. Those with a history of diabetes, CHD, stroke, or athero- sclerotic vascular disease were excluded.

The FRS was calculated for each participant to determine 10-year risk of CHD. Based on their FRS, patients were stratified into three risk categories: low (less than 6%), intermediate (6%-19%), and high (at least 20%). An abnormal ABI was defined as less than 0.9 and/or greater than 1.4 in either leg.

A low FRS was observed in 256 individuals (31%), and 414 (50%) had an intermediate risk, Dr. Dhangana said.

Risk prediction could be improved if abnormal ABI is used in screening.

Source Society of Interventional Radiology/www.SIRweb.org

Major Finding: 11.3% of individuals classified as low risk and 12.8% of individuals classified as intermediate risk using the Framingham Risk Score had an abnormal ankle brachial index.

Data Source: A multicenter cross-sectional study of 822 individuals conducted in conjunction with a national free public PAD screening program conducted at 23 sites during 2007-2009.

Disclosures: Dr. Dhanghana reported that he has no relevant financial relationships.

TAMPA — More than 10% of patients with low to intermediate risk for coronary heart disease have an abnormal ankle brachial index, putting them at a higher risk for myocardial infarction and coronary death than predicted by conventional measures.

In a study of 822 individuals screened for peripheral artery disease (PAD), 11% of those with a low-risk Framingham Risk Score (FRS) for coronary disease and 13% of those with an intermediate-risk score had an abnormal ankle brachial index (ABI).

Abnormal ABI has been associated with increased risk of coronary heart disease events and mortality, even in individuals at low to intermediate CHD risk (JAMA 2008;300:197-208).

However, prevalence estimates of abnormal ABI among older screening populations with low-intermediate FRS have not been reported previously, Dr. Raj Dhangana said at the annual meeting of the Society of Interventional Radiology.

“The prevalence of abnormal ABI is high, even in those a without high Framingham Risk Score. … The use of abnormal ABI in screening has the potential to improve risk prediction,” according to Dr. Dhangana.

The findings are good news, given that at least 60% of CHD events occur in individuals who were not known to be at high risk (BMJ 2003;327:1267). In fact, almost two-thirds of events occur in individuals who are either at low or intermediate risk using the FRS (Am. Heart J. 2002;144:95-100).

The use of ABI for screening could help improve risk prediction for CHD, said Dr. Dhangana, a research fellow at Rhode Island Hospital in Providence.

The researchers analyzed data from the PEDAL Study (Population-Based Examinations to Determine Ankle-Brachial Index)—a multicenter, cross-sectional study conducted at 23 sites of the Legs for Life national free public PAD screening program in 2007-2009.

Patients were included in the analysis if they were at least age 18 years and if their ABI and FRS variables were available. Those with a history of diabetes, CHD, stroke, or athero- sclerotic vascular disease were excluded.

The FRS was calculated for each participant to determine 10-year risk of CHD. Based on their FRS, patients were stratified into three risk categories: low (less than 6%), intermediate (6%-19%), and high (at least 20%). An abnormal ABI was defined as less than 0.9 and/or greater than 1.4 in either leg.

A low FRS was observed in 256 individuals (31%), and 414 (50%) had an intermediate risk, Dr. Dhangana said.

Risk prediction could be improved if abnormal ABI is used in screening.

Source Society of Interventional Radiology/www.SIRweb.org

Major Finding: 11.3% of individuals classified as low risk and 12.8% of individuals classified as intermediate risk using the Framingham Risk Score had an abnormal ankle brachial index.

Data Source: A multicenter cross-sectional study of 822 individuals conducted in conjunction with a national free public PAD screening program conducted at 23 sites during 2007-2009.

Disclosures: Dr. Dhanghana reported that he has no relevant financial relationships.

TAMPA — More than 10% of patients with low to intermediate risk for coronary heart disease have an abnormal ankle brachial index, putting them at a higher risk for myocardial infarction and coronary death than predicted by conventional measures.

In a study of 822 individuals screened for peripheral artery disease (PAD), 11% of those with a low-risk Framingham Risk Score (FRS) for coronary disease and 13% of those with an intermediate-risk score had an abnormal ankle brachial index (ABI).

Abnormal ABI has been associated with increased risk of coronary heart disease events and mortality, even in individuals at low to intermediate CHD risk (JAMA 2008;300:197-208).

However, prevalence estimates of abnormal ABI among older screening populations with low-intermediate FRS have not been reported previously, Dr. Raj Dhangana said at the annual meeting of the Society of Interventional Radiology.

“The prevalence of abnormal ABI is high, even in those a without high Framingham Risk Score. … The use of abnormal ABI in screening has the potential to improve risk prediction,” according to Dr. Dhangana.

The findings are good news, given that at least 60% of CHD events occur in individuals who were not known to be at high risk (BMJ 2003;327:1267). In fact, almost two-thirds of events occur in individuals who are either at low or intermediate risk using the FRS (Am. Heart J. 2002;144:95-100).

The use of ABI for screening could help improve risk prediction for CHD, said Dr. Dhangana, a research fellow at Rhode Island Hospital in Providence.

The researchers analyzed data from the PEDAL Study (Population-Based Examinations to Determine Ankle-Brachial Index)—a multicenter, cross-sectional study conducted at 23 sites of the Legs for Life national free public PAD screening program in 2007-2009.

Patients were included in the analysis if they were at least age 18 years and if their ABI and FRS variables were available. Those with a history of diabetes, CHD, stroke, or athero- sclerotic vascular disease were excluded.

The FRS was calculated for each participant to determine 10-year risk of CHD. Based on their FRS, patients were stratified into three risk categories: low (less than 6%), intermediate (6%-19%), and high (at least 20%). An abnormal ABI was defined as less than 0.9 and/or greater than 1.4 in either leg.

A low FRS was observed in 256 individuals (31%), and 414 (50%) had an intermediate risk, Dr. Dhangana said.

Risk prediction could be improved if abnormal ABI is used in screening.

Source Society of Interventional Radiology/www.SIRweb.org

GAITHERSBURG, MD. — Cancer therapies targeting specific genetic mutations could be required to have corresponding validated diagnostic tests before the therapies can gain approval in the United States, judging by the 7–1 vote of a Food and Drug Administration advisory committee.

The Oncologic Drugs Advisory Committee agreed with the agency that a validated test for the Bcr-Abl T3151 mutation is required before omacetaxine mepesuccinate (Omapro)—a drug targeting that mutation—can be considered for approval.

ChemGenex Pharmaceuticals, a company with offices in Australia and Menlo Park, Calif., is seeking approval of omacetaxine for the treatment of adults with chronic myeloid leukemia (CML) after failure on prior therapy with imatinib (Gleevec) and with the Bcr-Abl T3151 mutation.

ChemGenex announced later that it had received a complete response letter from the FDA, which did not ask for a new trial or data on additional patients. The company said that it hoped to meet with the FDA to address the issues raised by the advisory committee.

The vote is an important one in light of the growing number of therapies targeting specific genetic mutations. ODAC chair Dr. S. Gail Eckhardt noted that the indication for this drug is molecularly defined—failure on imatinib and the T3151 mutation—and that the question of related diagnostic tests will come up more frequently. Dr. Eckhardt is head of medical oncology at the University of Colorado in Denver.

The T3151 mutation is thought to be a marker of tyrosine kinase inhibitor resistance. Patients with the mutation do not respond to any of the three approved therapies for CML and have a poor prognosis. T3151 mutation testing is available at a number of laboratories but is not standardized among facilities.

Omacetaxine, a new molecular entity and first in a class of cephalotaxines, is a synthetic formulation of homoharringtonine, a drug isolated from the evergreen tree Cephalotaxus in China.

The application to the FDA was based on the response rates in a single-arm trial in 66 patients deemed to have the T3151 mutation. In the open-label phase II dosing study CML-202, patients were given subcutaneous omacetaxine 1.25 mg/m

Patients in chronic, accelerated, or myeloid blast phases of CML were included in the study.

Prior imatinib therapy had to have failed, and the T3151 mutation had to be identified and confirmed prior to study enrollment.

Study end points included major cytogenetic response or complete hematologic response for patients with chronic phase CML and overall hematologic response (complete hematologic response, no evidence of leukemia, return to chronic phase) for patients in the accelerated or blast phases.

The study included 40 patients in the chronic phase, 16 in the accelerated phase, and 10 in the blast phase.

All of the patients were determined to have the T3151 mutation, but only 43 had central laboratory confirmation of T3151 status, meaning that roughly a third of the patients failed to meet at least one of the study criteria.

Perhaps more importantly, 10 patients who were initially identified as having the T3151 mutation were later determined by the central laboratories not to have the mutation.

The agency's primary concern was the use of multiple assay methods for the detection of T3151 mutation without any bridging studies between the tests to assess reliability, reproducibility, and concordance of results.

“The lack of having a uniform in vitro diagnostic test creates uncertainty about patient selection both in this trial and, more importantly, in a post-approval setting,” the agency wrote in its charge to the committee.

The majority of panel members expressed the same concerns.

The agency also expressed concern that the results of a small, single-arm incomplete efficacy trial were insufficient for approval, given uncertainty in response determination and duration, and uncertainty of the clinical meaningfulness of response rates.

Among patients in the chronic phase, 25% had a major cytogenetic response with 6-month duration, and 85% had a complete hematologic response with 10-month duration.

Among those in the accelerated phase, 37% had an overall hematologic response with a 7-month duration.

Among those in the blast phase, 30% had an overall hematologic response with a 2-month duration.

However, several committee members noted that the numbers of patients, particularly in the accelerated and blast groups, were too small for meaningful analysis.

Disclosures: Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting.

GAITHERSBURG, MD. — Cancer therapies targeting specific genetic mutations could be required to have corresponding validated diagnostic tests before the therapies can gain approval in the United States, judging by the 7–1 vote of a Food and Drug Administration advisory committee.

The Oncologic Drugs Advisory Committee agreed with the agency that a validated test for the Bcr-Abl T3151 mutation is required before omacetaxine mepesuccinate (Omapro)—a drug targeting that mutation—can be considered for approval.

ChemGenex Pharmaceuticals, a company with offices in Australia and Menlo Park, Calif., is seeking approval of omacetaxine for the treatment of adults with chronic myeloid leukemia (CML) after failure on prior therapy with imatinib (Gleevec) and with the Bcr-Abl T3151 mutation.

ChemGenex announced later that it had received a complete response letter from the FDA, which did not ask for a new trial or data on additional patients. The company said that it hoped to meet with the FDA to address the issues raised by the advisory committee.

The vote is an important one in light of the growing number of therapies targeting specific genetic mutations. ODAC chair Dr. S. Gail Eckhardt noted that the indication for this drug is molecularly defined—failure on imatinib and the T3151 mutation—and that the question of related diagnostic tests will come up more frequently. Dr. Eckhardt is head of medical oncology at the University of Colorado in Denver.

The T3151 mutation is thought to be a marker of tyrosine kinase inhibitor resistance. Patients with the mutation do not respond to any of the three approved therapies for CML and have a poor prognosis. T3151 mutation testing is available at a number of laboratories but is not standardized among facilities.

Omacetaxine, a new molecular entity and first in a class of cephalotaxines, is a synthetic formulation of homoharringtonine, a drug isolated from the evergreen tree Cephalotaxus in China.

The application to the FDA was based on the response rates in a single-arm trial in 66 patients deemed to have the T3151 mutation. In the open-label phase II dosing study CML-202, patients were given subcutaneous omacetaxine 1.25 mg/m

Patients in chronic, accelerated, or myeloid blast phases of CML were included in the study.

Prior imatinib therapy had to have failed, and the T3151 mutation had to be identified and confirmed prior to study enrollment.

Study end points included major cytogenetic response or complete hematologic response for patients with chronic phase CML and overall hematologic response (complete hematologic response, no evidence of leukemia, return to chronic phase) for patients in the accelerated or blast phases.

The study included 40 patients in the chronic phase, 16 in the accelerated phase, and 10 in the blast phase.

All of the patients were determined to have the T3151 mutation, but only 43 had central laboratory confirmation of T3151 status, meaning that roughly a third of the patients failed to meet at least one of the study criteria.

Perhaps more importantly, 10 patients who were initially identified as having the T3151 mutation were later determined by the central laboratories not to have the mutation.

The agency's primary concern was the use of multiple assay methods for the detection of T3151 mutation without any bridging studies between the tests to assess reliability, reproducibility, and concordance of results.

“The lack of having a uniform in vitro diagnostic test creates uncertainty about patient selection both in this trial and, more importantly, in a post-approval setting,” the agency wrote in its charge to the committee.

The majority of panel members expressed the same concerns.

The agency also expressed concern that the results of a small, single-arm incomplete efficacy trial were insufficient for approval, given uncertainty in response determination and duration, and uncertainty of the clinical meaningfulness of response rates.

Among patients in the chronic phase, 25% had a major cytogenetic response with 6-month duration, and 85% had a complete hematologic response with 10-month duration.

Among those in the accelerated phase, 37% had an overall hematologic response with a 7-month duration.

Among those in the blast phase, 30% had an overall hematologic response with a 2-month duration.

However, several committee members noted that the numbers of patients, particularly in the accelerated and blast groups, were too small for meaningful analysis.

Disclosures: Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting.

GAITHERSBURG, MD. — Cancer therapies targeting specific genetic mutations could be required to have corresponding validated diagnostic tests before the therapies can gain approval in the United States, judging by the 7–1 vote of a Food and Drug Administration advisory committee.

The Oncologic Drugs Advisory Committee agreed with the agency that a validated test for the Bcr-Abl T3151 mutation is required before omacetaxine mepesuccinate (Omapro)—a drug targeting that mutation—can be considered for approval.

ChemGenex Pharmaceuticals, a company with offices in Australia and Menlo Park, Calif., is seeking approval of omacetaxine for the treatment of adults with chronic myeloid leukemia (CML) after failure on prior therapy with imatinib (Gleevec) and with the Bcr-Abl T3151 mutation.

ChemGenex announced later that it had received a complete response letter from the FDA, which did not ask for a new trial or data on additional patients. The company said that it hoped to meet with the FDA to address the issues raised by the advisory committee.

The vote is an important one in light of the growing number of therapies targeting specific genetic mutations. ODAC chair Dr. S. Gail Eckhardt noted that the indication for this drug is molecularly defined—failure on imatinib and the T3151 mutation—and that the question of related diagnostic tests will come up more frequently. Dr. Eckhardt is head of medical oncology at the University of Colorado in Denver.

The T3151 mutation is thought to be a marker of tyrosine kinase inhibitor resistance. Patients with the mutation do not respond to any of the three approved therapies for CML and have a poor prognosis. T3151 mutation testing is available at a number of laboratories but is not standardized among facilities.

Omacetaxine, a new molecular entity and first in a class of cephalotaxines, is a synthetic formulation of homoharringtonine, a drug isolated from the evergreen tree Cephalotaxus in China.

The application to the FDA was based on the response rates in a single-arm trial in 66 patients deemed to have the T3151 mutation. In the open-label phase II dosing study CML-202, patients were given subcutaneous omacetaxine 1.25 mg/m

Patients in chronic, accelerated, or myeloid blast phases of CML were included in the study.

Prior imatinib therapy had to have failed, and the T3151 mutation had to be identified and confirmed prior to study enrollment.

Study end points included major cytogenetic response or complete hematologic response for patients with chronic phase CML and overall hematologic response (complete hematologic response, no evidence of leukemia, return to chronic phase) for patients in the accelerated or blast phases.

The study included 40 patients in the chronic phase, 16 in the accelerated phase, and 10 in the blast phase.

All of the patients were determined to have the T3151 mutation, but only 43 had central laboratory confirmation of T3151 status, meaning that roughly a third of the patients failed to meet at least one of the study criteria.

Perhaps more importantly, 10 patients who were initially identified as having the T3151 mutation were later determined by the central laboratories not to have the mutation.

The agency's primary concern was the use of multiple assay methods for the detection of T3151 mutation without any bridging studies between the tests to assess reliability, reproducibility, and concordance of results.

“The lack of having a uniform in vitro diagnostic test creates uncertainty about patient selection both in this trial and, more importantly, in a post-approval setting,” the agency wrote in its charge to the committee.

The majority of panel members expressed the same concerns.

The agency also expressed concern that the results of a small, single-arm incomplete efficacy trial were insufficient for approval, given uncertainty in response determination and duration, and uncertainty of the clinical meaningfulness of response rates.

Among patients in the chronic phase, 25% had a major cytogenetic response with 6-month duration, and 85% had a complete hematologic response with 10-month duration.

Among those in the accelerated phase, 37% had an overall hematologic response with a 7-month duration.

Among those in the blast phase, 30% had an overall hematologic response with a 2-month duration.

However, several committee members noted that the numbers of patients, particularly in the accelerated and blast groups, were too small for meaningful analysis.

Disclosures: Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting.

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005.

In the oldest age groups, “there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The researchers identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices, and by a sampling of nursing homes and physician offices.<The medical record abstract for each potential case was reviewed by a study physician.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population, using U.S. Census population data.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference, which was sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

Regarding risk factors, both diabetes and coronary heart disease significantly increased between 1995 and 2005 in those aged 20-44. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years<[pn

Disclosures: The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela and his coinvestigators reported no relevant financial relationships.

Go to youtube.com/ElsGlobalMedicalNews

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005.

In the oldest age groups, “there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The researchers identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices, and by a sampling of nursing homes and physician offices.<The medical record abstract for each potential case was reviewed by a study physician.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population, using U.S. Census population data.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference, which was sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

Regarding risk factors, both diabetes and coronary heart disease significantly increased between 1995 and 2005 in those aged 20-44. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years<[pn

Disclosures: The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela and his coinvestigators reported no relevant financial relationships.

Go to youtube.com/ElsGlobalMedicalNews

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005.

In the oldest age groups, “there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The researchers identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices, and by a sampling of nursing homes and physician offices.<The medical record abstract for each potential case was reviewed by a study physician.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population, using U.S. Census population data.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference, which was sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

Regarding risk factors, both diabetes and coronary heart disease significantly increased between 1995 and 2005 in those aged 20-44. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years<[pn

Disclosures: The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela and his coinvestigators reported no relevant financial relationships.

Go to youtube.com/ElsGlobalMedicalNews

Major Finding: Cilostazol reduced the risk of secondary stroke by 25.7%, compared with aspirin.

Data Source: A postmarketing study of 2,757 noncardioembolic stroke patients.

Disclosures: The study was sponsored by Otsuka Pharma, which makes cilostazol. Dr. Shinohara reported that he has received speaking fees from several pharmaceutical companies, including Otsuka, and is a consultant to Schering-Plough KK and Pfizer Japan.

SAN ANTONIO — The antiplatelet drug cilostazol appears to surpass aspirin in secondary stroke prevention with less risk of bleeding, based on the results of a Japanese study of more than 2,700 stroke patients.

Cilostazol (Pletal) significantly reduced the risk of symptomatic stroke by a quarter (25.7%), compared with aspirin in the Cilostazol Stroke Prevention Study 2 (CSPS-2), Dr. Yukito Shinohara said at the International Stroke Conference.

There were 82 symptomatic strokes among patients on cilostazol, compared with 119 in patients on aspirin, as determined by clinical assessment and CT/MRI. Symptomatic stroke (cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage) was the study's primary end point.

Not only do the results show the noninferiority of cilostazol to aspirin for secondary stroke prevention, but the drug is also significantly more effective than aspirin for preventing recurrent stroke, said Dr. Shinohara, who is a neurologist at Tachikawa Hospital in Tokyo.

“Cilostazol is recommended as an option for the prevention of stroke recurrence in noncardioembolic stroke patients who can tolerate long-term administration of this drug.”

Cilostazol is a phosphodiesterase III inhibitor and is approved in the United States for the reduction of symptoms of intermittent claudication. While the mechanism of action is not fully understood, the drug reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, collagen, arachidonic acid, epinephrine, and shear stress.

In the study, 2,757 noncardioembolic stroke patients were randomized to receive either 100 mg cilostazol twice daily or 81 mg aspirin once daily. Patients were treated for 1-5 years.

Secondary end points included cerebral infarction, ischemic cerebrovascular disorder, and death from any cause.

The efficacy and safety analyses included 1,337 patients on cilostazol and 1,335 on aspirin. The groups had comparable baseline characteristics.

Cilostazol also reduced the secondary end points, compared with aspirin, but the differences did not reach significance.

However, cilostazol did reduce the risk of a cluster of secondary events by 20%. The cluster included cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack, angina pectoris, myocardial infarction, heart failure, and hemorrhage requiring hospitalization. The combined number of these cluster events was 138 for those on cilostazol and 186 for those on aspirin.

Patients on cilostazol also had significantly fewer bleeding events—23, compared with 57 for those on aspirin.

Headache, diarrhea, palpitations, dizziness, and tachycardia each occurred significantly more often among patients on cilostazol. However, hypertension and constipation occurred significantly more often among patients on aspirin.

Discontinuation because of drug-related adverse events occurred in 20% of patients on cilostazol, compared with 12% in patients on aspirin.

Major Finding: Cilostazol reduced the risk of secondary stroke by 25.7%, compared with aspirin.

Data Source: A postmarketing study of 2,757 noncardioembolic stroke patients.

Disclosures: The study was sponsored by Otsuka Pharma, which makes cilostazol. Dr. Shinohara reported that he has received speaking fees from several pharmaceutical companies, including Otsuka, and is a consultant to Schering-Plough KK and Pfizer Japan.

SAN ANTONIO — The antiplatelet drug cilostazol appears to surpass aspirin in secondary stroke prevention with less risk of bleeding, based on the results of a Japanese study of more than 2,700 stroke patients.

Cilostazol (Pletal) significantly reduced the risk of symptomatic stroke by a quarter (25.7%), compared with aspirin in the Cilostazol Stroke Prevention Study 2 (CSPS-2), Dr. Yukito Shinohara said at the International Stroke Conference.

There were 82 symptomatic strokes among patients on cilostazol, compared with 119 in patients on aspirin, as determined by clinical assessment and CT/MRI. Symptomatic stroke (cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage) was the study's primary end point.

Not only do the results show the noninferiority of cilostazol to aspirin for secondary stroke prevention, but the drug is also significantly more effective than aspirin for preventing recurrent stroke, said Dr. Shinohara, who is a neurologist at Tachikawa Hospital in Tokyo.

“Cilostazol is recommended as an option for the prevention of stroke recurrence in noncardioembolic stroke patients who can tolerate long-term administration of this drug.”

Cilostazol is a phosphodiesterase III inhibitor and is approved in the United States for the reduction of symptoms of intermittent claudication. While the mechanism of action is not fully understood, the drug reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, collagen, arachidonic acid, epinephrine, and shear stress.

In the study, 2,757 noncardioembolic stroke patients were randomized to receive either 100 mg cilostazol twice daily or 81 mg aspirin once daily. Patients were treated for 1-5 years.

Secondary end points included cerebral infarction, ischemic cerebrovascular disorder, and death from any cause.

The efficacy and safety analyses included 1,337 patients on cilostazol and 1,335 on aspirin. The groups had comparable baseline characteristics.

Cilostazol also reduced the secondary end points, compared with aspirin, but the differences did not reach significance.

However, cilostazol did reduce the risk of a cluster of secondary events by 20%. The cluster included cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack, angina pectoris, myocardial infarction, heart failure, and hemorrhage requiring hospitalization. The combined number of these cluster events was 138 for those on cilostazol and 186 for those on aspirin.

Patients on cilostazol also had significantly fewer bleeding events—23, compared with 57 for those on aspirin.

Headache, diarrhea, palpitations, dizziness, and tachycardia each occurred significantly more often among patients on cilostazol. However, hypertension and constipation occurred significantly more often among patients on aspirin.

Discontinuation because of drug-related adverse events occurred in 20% of patients on cilostazol, compared with 12% in patients on aspirin.

Major Finding: Cilostazol reduced the risk of secondary stroke by 25.7%, compared with aspirin.

Data Source: A postmarketing study of 2,757 noncardioembolic stroke patients.

Disclosures: The study was sponsored by Otsuka Pharma, which makes cilostazol. Dr. Shinohara reported that he has received speaking fees from several pharmaceutical companies, including Otsuka, and is a consultant to Schering-Plough KK and Pfizer Japan.

SAN ANTONIO — The antiplatelet drug cilostazol appears to surpass aspirin in secondary stroke prevention with less risk of bleeding, based on the results of a Japanese study of more than 2,700 stroke patients.

Cilostazol (Pletal) significantly reduced the risk of symptomatic stroke by a quarter (25.7%), compared with aspirin in the Cilostazol Stroke Prevention Study 2 (CSPS-2), Dr. Yukito Shinohara said at the International Stroke Conference.

There were 82 symptomatic strokes among patients on cilostazol, compared with 119 in patients on aspirin, as determined by clinical assessment and CT/MRI. Symptomatic stroke (cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage) was the study's primary end point.

Not only do the results show the noninferiority of cilostazol to aspirin for secondary stroke prevention, but the drug is also significantly more effective than aspirin for preventing recurrent stroke, said Dr. Shinohara, who is a neurologist at Tachikawa Hospital in Tokyo.

“Cilostazol is recommended as an option for the prevention of stroke recurrence in noncardioembolic stroke patients who can tolerate long-term administration of this drug.”

Cilostazol is a phosphodiesterase III inhibitor and is approved in the United States for the reduction of symptoms of intermittent claudication. While the mechanism of action is not fully understood, the drug reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, collagen, arachidonic acid, epinephrine, and shear stress.

In the study, 2,757 noncardioembolic stroke patients were randomized to receive either 100 mg cilostazol twice daily or 81 mg aspirin once daily. Patients were treated for 1-5 years.

Secondary end points included cerebral infarction, ischemic cerebrovascular disorder, and death from any cause.

The efficacy and safety analyses included 1,337 patients on cilostazol and 1,335 on aspirin. The groups had comparable baseline characteristics.

Cilostazol also reduced the secondary end points, compared with aspirin, but the differences did not reach significance.

However, cilostazol did reduce the risk of a cluster of secondary events by 20%. The cluster included cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack, angina pectoris, myocardial infarction, heart failure, and hemorrhage requiring hospitalization. The combined number of these cluster events was 138 for those on cilostazol and 186 for those on aspirin.

Patients on cilostazol also had significantly fewer bleeding events—23, compared with 57 for those on aspirin.

Headache, diarrhea, palpitations, dizziness, and tachycardia each occurred significantly more often among patients on cilostazol. However, hypertension and constipation occurred significantly more often among patients on aspirin.

Discontinuation because of drug-related adverse events occurred in 20% of patients on cilostazol, compared with 12% in patients on aspirin.

Major Finding: Conventional risk factors accounted for only 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, reported George Howard, Dr.P.H., at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence among blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It's estimated that blacks have a 40% greater stroke mortality rate than do whites, he noted. This difference is comparable to all blacks having hypertension and diabetes and no whites having either risk factor, Dr. Howard said. “These are massive differences in mortality.”

Study participants were selected from a commercially available list and were recruited by mail and telephone. The researchers used a computer-assisted telephone interview that includes cardiovascular disease history. Thisiwas followed by a home visit for venipuncture, ECG, and physical measures.

Participants were followed at 6-month intervals for stroke surveillance. Suspected eventsawere adjudicated centrally. Currently, therearere 352 events among 26,610 participants, who were stroke- and/or TIA-free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk of blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence among blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard observed.

The researchers plan to look for other explanations for the racial differences seen in stroke incidence. They speculate that blacks may have more severe and/or earlier development of risk factors. There may also be nonconventional factors at play.

Major Finding: Conventional risk factors accounted for only 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, reported George Howard, Dr.P.H., at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence among blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It's estimated that blacks have a 40% greater stroke mortality rate than do whites, he noted. This difference is comparable to all blacks having hypertension and diabetes and no whites having either risk factor, Dr. Howard said. “These are massive differences in mortality.”

Study participants were selected from a commercially available list and were recruited by mail and telephone. The researchers used a computer-assisted telephone interview that includes cardiovascular disease history. Thisiwas followed by a home visit for venipuncture, ECG, and physical measures.

Participants were followed at 6-month intervals for stroke surveillance. Suspected eventsawere adjudicated centrally. Currently, therearere 352 events among 26,610 participants, who were stroke- and/or TIA-free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk of blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence among blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard observed.

The researchers plan to look for other explanations for the racial differences seen in stroke incidence. They speculate that blacks may have more severe and/or earlier development of risk factors. There may also be nonconventional factors at play.

Major Finding: Conventional risk factors accounted for only 13% of the excess incidence of stroke among blacks, whereas the addition of socioeconomic status to the analysis accounted for 23%.

Data Source: A population-based study of more than 30,000 white and black participants.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Howard reported that he has no relevant financial relationships.

SAN ANTONIO — Although large racial differences in conventional risk factors for cerebrovascular disease and socioeconomic factors exist, these differences do not fully account for the greater incidence of stroke that is seen in blacks.

In a proportional hazards mediation analysis, at age 45 years the addition of conventional risk factors accounted for 13% of the excess incidence among blacks, reported George Howard, Dr.P.H., at the annual International Stroke Conference. The addition of socioeconomic status to the analysis accounts for 23% of the excess incidence among blacks.

“The things that we tend to think about as largely driving the black-white differences account for less than a quarter of the differences that we're observing,” said Dr. Howard, chair of biostatistics at the University of Alabama at Birmingham.

The findings come from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, which involves a national cohort of 30,239 white and black participants.

“One of the great mysteries in stroke is the huge racial disparities in stroke mortality,” Dr. Howard said.

It's estimated that blacks have a 40% greater stroke mortality rate than do whites, he noted. This difference is comparable to all blacks having hypertension and diabetes and no whites having either risk factor, Dr. Howard said. “These are massive differences in mortality.”

Study participants were selected from a commercially available list and were recruited by mail and telephone. The researchers used a computer-assisted telephone interview that includes cardiovascular disease history. Thisiwas followed by a home visit for venipuncture, ECG, and physical measures.

Participants were followed at 6-month intervals for stroke surveillance. Suspected eventsawere adjudicated centrally. Currently, therearere 352 events among 26,610 participants, who were stroke- and/or TIA-free at baseline.

In this study, the researchers performed a proportional hazards mediation analysis, estimating the excess risk of blacks, adjusting for possible factors, and evaluating how much of the excess risk is accounted for by the inclusion of these factors.

The REGARDS population is generally reflective of the U.S. population. The assessed demographic factors included age, sex, and region. Risk factors included hypertension, diabetes, atrial fibrillation, dyslipidemia, previous MI, current smoking, alcohol use, and weekly exercise. Socioeconomic factors included education and income.

In terms of risk factors, 70% of blacks had hypertension, compared with 49% of whites. Likewise, 29% of blacks had diabetes, compared with 15% of whites.

A clear age effect has been observed as well, with a 300% stroke mortality rate for blacks younger than 65 years.

In this analysis, at age 65 the addition of risk factors accounted for 31% of the excess incidence among blacks. The addition of socioeconomic status accounts for 42% of the excess incidence among blacks.

“Depending on the age, these factors account for less than half of the racial disparity in incidence. So something else is accounting for the other half,” Dr. Howard observed.

The researchers plan to look for other explanations for the racial differences seen in stroke incidence. They speculate that blacks may have more severe and/or earlier development of risk factors. There may also be nonconventional factors at play.

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false-negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. To ensure that a malignant melanoma will eventually be found, both periodic total body examinations by a physician and regular patient self-examinations are key.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception: Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist, a partial biopsy not capturing the most diagnostically relevant part of the lesion, malignant melanoma being misdiagnosed as a dysplastic or spitz nevus, unrecognized desmoplastic malignant melanoma, and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed these common scenarios:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, Dr. Marghoob noted.

To track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. Dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” Dr. Marghoob said. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion that was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, Dr. Marghoob said.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For banal-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, Dr. Marghoob said.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Disclosures: Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Partial biopsies of this melanoma yielded results ranging from Clark's nevus to invasive melanoma.

Source Images courtesy Dr. Ashfaq A. Marghoob

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false-negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. To ensure that a malignant melanoma will eventually be found, both periodic total body examinations by a physician and regular patient self-examinations are key.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception: Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist, a partial biopsy not capturing the most diagnostically relevant part of the lesion, malignant melanoma being misdiagnosed as a dysplastic or spitz nevus, unrecognized desmoplastic malignant melanoma, and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed these common scenarios:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, Dr. Marghoob noted.

To track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. Dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” Dr. Marghoob said. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion that was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, Dr. Marghoob said.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For banal-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, Dr. Marghoob said.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Disclosures: Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Partial biopsies of this melanoma yielded results ranging from Clark's nevus to invasive melanoma.

Source Images courtesy Dr. Ashfaq A. Marghoob

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false-negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. To ensure that a malignant melanoma will eventually be found, both periodic total body examinations by a physician and regular patient self-examinations are key.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception: Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist, a partial biopsy not capturing the most diagnostically relevant part of the lesion, malignant melanoma being misdiagnosed as a dysplastic or spitz nevus, unrecognized desmoplastic malignant melanoma, and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed these common scenarios:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, Dr. Marghoob noted.

To track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. Dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” Dr. Marghoob said. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion that was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, Dr. Marghoob said.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For banal-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, Dr. Marghoob said.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Disclosures: Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Partial biopsies of this melanoma yielded results ranging from Clark's nevus to invasive melanoma.

Source Images courtesy Dr. Ashfaq A. Marghoob

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005. (See table for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in five counties. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, identify the subtype of stroke, and review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela said at the conference, sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

They looked at the prevalence of risk factors using data from population-based telephone surveys of the region that were linked to the three study periods and were performed in 1995, 2000, and 2001.

Among those aged 20-44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years.

The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela reported that he and his coinvestigators have no relevant financial relationships.

Ischemic strokes outnumbered hemorrhagic strokes in those aged younger than 45.

Source DR. KISSELA

Source Elsevier Global Medical News

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005. (See table for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in five counties. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, identify the subtype of stroke, and review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela said at the conference, sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

They looked at the prevalence of risk factors using data from population-based telephone surveys of the region that were linked to the three study periods and were performed in 1995, 2000, and 2001.

Among those aged 20-44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years.

The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela reported that he and his coinvestigators have no relevant financial relationships.

Ischemic strokes outnumbered hemorrhagic strokes in those aged younger than 45.

Source DR. KISSELA

Source Elsevier Global Medical News

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993-1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993-1994 to 5.5% in 1999 and to 7.3% in 2005. (See table for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in five counties. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, identify the subtype of stroke, and review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. Stroke was defined as a focal neurologic deficit referable to a vascular territory and lasting longer than 24 hours. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000.

There were 1,907 strokes in 1993-1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela said at the conference, sponsored by the American Heart Association.

One possible explanation for increasing strokes among younger age groups might be an increase in hemorrhagic strokes. However, when the researchers looked at this, they found that ischemic strokes outnumbered hemorrhagic strokes (intracranial and subarachnoid hemorrhage) in those aged younger than 45 years in all three time periods, and even seemed to increase in 2005.

They looked at the prevalence of risk factors using data from population-based telephone surveys of the region that were linked to the three study periods and were performed in 1995, 2000, and 2001.

Among those aged 20-44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45-54 years.

The study is funded by the National Institute of Neurological Disorders and Stroke. Dr. Kissela reported that he and his coinvestigators have no relevant financial relationships.

Ischemic strokes outnumbered hemorrhagic strokes in those aged younger than 45.

Source DR. KISSELA

Source Elsevier Global Medical News