Sharon Worcester

The progression to systemic lupus in this patient is a “fascinating example of the spectrum of clinical presentation and chronicity in systemic lupus erythematosus,” Dr. Sheilagh Maguiness said at a meeting of the Society for Pediatric Dermatology.

Although neither the boy nor his mother reported his history of disease at birth or infancy—and in fact initially denied any such history or related family history—a chance consultation with Dr. Ilona Frieden of the University of California, San Francisco, who was familiar with the patient and had reported on the case in 1998, shed light on his condition.

He was born to a 22-year-old mother at 35 weeks' gestation with a widespread rash consisting of reticulate atrophic plaques, hyperpigmentation, desquamation, and alopecia.

Hematologic abnormalities at that time included pancytopenia; positive antinuclear antibodies (ANA); and negative Ro, La, and anticardiolipin antibody titres. The mother also had positive ANA and was negative for Ro/La, said Dr. Maguiness, also of the university.

A skin biopsy shortly after birth revealed atrophic epidermis with areas of vacuolar interface dermatitis and increased mucin. Direct immunofluorescence showed granular IgG at the dermoepidermal junction, and the diagnosis of congenital lupus erythematosus was made, she said.

The patient's early disease course included three hospitalizations during infancy for inguinal hernia repair, respiratory distress, and exacerbation of cutaneous lesions. During the final hospitalization, the patient's ANA remained positive and double-stranded DNA became positive. He improved gradually after treatment with intravenous immunoglobulin, and had no evidence of recurrent disease at a follow-up visit at age 5 years. He was lost to follow-up until presenting at age 15.

At that time, he had an extensive rash and several other symptoms, including arthritis, headaches, and high blood pressure.

“He had widespread, hyperpigmented, annular, atrophic, hyperkeratotic lesions over sun-exposed areas,” Dr. Maguiness said, noting he also had diffuse alopecia.

There was an unusual background of hypo- and depigmentation over his trunk, which, according to the patient, had been present since birth but looked like partially treated vitiligo, she said.

Multiple investigations revealed strongly positive ANA, anti-Ro/La antibodies, positive small nuclear ribonucleoproteins, and renal involvement. A biopsy indicated class II lupus nephritis.

A biopsy of the upper outer arm that was taken to confirm the diagnosis showed an acute interface dermatitis with vacuolar changes, necrotic keratinocytes, parakeratosis, and a positive direct immunofluorescence, leading to the diagnosis of SLE with extensive cutaneous involvement.

The patient was hospitalized and treated with pulse Solu-Medrol, hydroxychloroquine, antihypertensives, and topical steroids, Dr. Maguiness noted.

His renal disease has remained stable, but the cutaneous aspect of his disease has been difficult to control despite immunosuppression, she said.

Mainly, the patient has had discoid and subacute cutaneous lupus erythematosus-type lesions. In December, however, he experienced a cutaneous exacerbation with more target lesions, despite having no history of herpes simplex infection. He had violaceous plaques with some desquamation and involvement of the palms and soles. His mucous membranes were clear.

Another biopsy from his trunk at this presentation showed vacuolar interface dermatitis with subdermal clefting and numerous necrotic keratinocytes, which could be consistent with either bullous lupus erythematosus or bullous erythema multiforme.

Direct immunofluorescence in this exacerbation was negative (previously it was positive), suggesting a diagnosis of Rowell's syndrome, which “very basically is erythema multiforme occurring in the setting of systemic lupus,” she said.

“Our patient's case … raises interesting questions about this congenital presentation of lupus. It is unusual for patients with typical neonatal lupus to develop SLE later on. This case makes one wonder if maybe that we should be questioning the sole role of maternal autoantibodies in this patient's case of congenital lupus. Perhaps he had some endogenous predisposition to develop lupus. This is the first patient we have observed with the clinical presentation of congenital, neonatal, and infantile lupus progressing to systemic lupus erythematosus as a teenager,” Dr. Maguiness said.

Discoid, hyperkeratotic, and hyperpig-mented plaques are seen on teen's face.

Biopsy shows interface dermatitis, necrotic keratinocytes, and subepidermal clefting. Photos courtesy Dr. Sheilagh Maguiness

The progression to systemic lupus in this patient is a “fascinating example of the spectrum of clinical presentation and chronicity in systemic lupus erythematosus,” Dr. Sheilagh Maguiness said at a meeting of the Society for Pediatric Dermatology.

Although neither the boy nor his mother reported his history of disease at birth or infancy—and in fact initially denied any such history or related family history—a chance consultation with Dr. Ilona Frieden of the University of California, San Francisco, who was familiar with the patient and had reported on the case in 1998, shed light on his condition.

He was born to a 22-year-old mother at 35 weeks' gestation with a widespread rash consisting of reticulate atrophic plaques, hyperpigmentation, desquamation, and alopecia.

Hematologic abnormalities at that time included pancytopenia; positive antinuclear antibodies (ANA); and negative Ro, La, and anticardiolipin antibody titres. The mother also had positive ANA and was negative for Ro/La, said Dr. Maguiness, also of the university.

A skin biopsy shortly after birth revealed atrophic epidermis with areas of vacuolar interface dermatitis and increased mucin. Direct immunofluorescence showed granular IgG at the dermoepidermal junction, and the diagnosis of congenital lupus erythematosus was made, she said.

The patient's early disease course included three hospitalizations during infancy for inguinal hernia repair, respiratory distress, and exacerbation of cutaneous lesions. During the final hospitalization, the patient's ANA remained positive and double-stranded DNA became positive. He improved gradually after treatment with intravenous immunoglobulin, and had no evidence of recurrent disease at a follow-up visit at age 5 years. He was lost to follow-up until presenting at age 15.

At that time, he had an extensive rash and several other symptoms, including arthritis, headaches, and high blood pressure.

“He had widespread, hyperpigmented, annular, atrophic, hyperkeratotic lesions over sun-exposed areas,” Dr. Maguiness said, noting he also had diffuse alopecia.

There was an unusual background of hypo- and depigmentation over his trunk, which, according to the patient, had been present since birth but looked like partially treated vitiligo, she said.

Multiple investigations revealed strongly positive ANA, anti-Ro/La antibodies, positive small nuclear ribonucleoproteins, and renal involvement. A biopsy indicated class II lupus nephritis.

A biopsy of the upper outer arm that was taken to confirm the diagnosis showed an acute interface dermatitis with vacuolar changes, necrotic keratinocytes, parakeratosis, and a positive direct immunofluorescence, leading to the diagnosis of SLE with extensive cutaneous involvement.

The patient was hospitalized and treated with pulse Solu-Medrol, hydroxychloroquine, antihypertensives, and topical steroids, Dr. Maguiness noted.

His renal disease has remained stable, but the cutaneous aspect of his disease has been difficult to control despite immunosuppression, she said.

Mainly, the patient has had discoid and subacute cutaneous lupus erythematosus-type lesions. In December, however, he experienced a cutaneous exacerbation with more target lesions, despite having no history of herpes simplex infection. He had violaceous plaques with some desquamation and involvement of the palms and soles. His mucous membranes were clear.

Another biopsy from his trunk at this presentation showed vacuolar interface dermatitis with subdermal clefting and numerous necrotic keratinocytes, which could be consistent with either bullous lupus erythematosus or bullous erythema multiforme.

Direct immunofluorescence in this exacerbation was negative (previously it was positive), suggesting a diagnosis of Rowell's syndrome, which “very basically is erythema multiforme occurring in the setting of systemic lupus,” she said.

“Our patient's case … raises interesting questions about this congenital presentation of lupus. It is unusual for patients with typical neonatal lupus to develop SLE later on. This case makes one wonder if maybe that we should be questioning the sole role of maternal autoantibodies in this patient's case of congenital lupus. Perhaps he had some endogenous predisposition to develop lupus. This is the first patient we have observed with the clinical presentation of congenital, neonatal, and infantile lupus progressing to systemic lupus erythematosus as a teenager,” Dr. Maguiness said.

Discoid, hyperkeratotic, and hyperpig-mented plaques are seen on teen's face.

Biopsy shows interface dermatitis, necrotic keratinocytes, and subepidermal clefting. Photos courtesy Dr. Sheilagh Maguiness

The progression to systemic lupus in this patient is a “fascinating example of the spectrum of clinical presentation and chronicity in systemic lupus erythematosus,” Dr. Sheilagh Maguiness said at a meeting of the Society for Pediatric Dermatology.

Although neither the boy nor his mother reported his history of disease at birth or infancy—and in fact initially denied any such history or related family history—a chance consultation with Dr. Ilona Frieden of the University of California, San Francisco, who was familiar with the patient and had reported on the case in 1998, shed light on his condition.

He was born to a 22-year-old mother at 35 weeks' gestation with a widespread rash consisting of reticulate atrophic plaques, hyperpigmentation, desquamation, and alopecia.

Hematologic abnormalities at that time included pancytopenia; positive antinuclear antibodies (ANA); and negative Ro, La, and anticardiolipin antibody titres. The mother also had positive ANA and was negative for Ro/La, said Dr. Maguiness, also of the university.

A skin biopsy shortly after birth revealed atrophic epidermis with areas of vacuolar interface dermatitis and increased mucin. Direct immunofluorescence showed granular IgG at the dermoepidermal junction, and the diagnosis of congenital lupus erythematosus was made, she said.

The patient's early disease course included three hospitalizations during infancy for inguinal hernia repair, respiratory distress, and exacerbation of cutaneous lesions. During the final hospitalization, the patient's ANA remained positive and double-stranded DNA became positive. He improved gradually after treatment with intravenous immunoglobulin, and had no evidence of recurrent disease at a follow-up visit at age 5 years. He was lost to follow-up until presenting at age 15.

At that time, he had an extensive rash and several other symptoms, including arthritis, headaches, and high blood pressure.

“He had widespread, hyperpigmented, annular, atrophic, hyperkeratotic lesions over sun-exposed areas,” Dr. Maguiness said, noting he also had diffuse alopecia.

There was an unusual background of hypo- and depigmentation over his trunk, which, according to the patient, had been present since birth but looked like partially treated vitiligo, she said.

Multiple investigations revealed strongly positive ANA, anti-Ro/La antibodies, positive small nuclear ribonucleoproteins, and renal involvement. A biopsy indicated class II lupus nephritis.

A biopsy of the upper outer arm that was taken to confirm the diagnosis showed an acute interface dermatitis with vacuolar changes, necrotic keratinocytes, parakeratosis, and a positive direct immunofluorescence, leading to the diagnosis of SLE with extensive cutaneous involvement.

The patient was hospitalized and treated with pulse Solu-Medrol, hydroxychloroquine, antihypertensives, and topical steroids, Dr. Maguiness noted.

His renal disease has remained stable, but the cutaneous aspect of his disease has been difficult to control despite immunosuppression, she said.

Mainly, the patient has had discoid and subacute cutaneous lupus erythematosus-type lesions. In December, however, he experienced a cutaneous exacerbation with more target lesions, despite having no history of herpes simplex infection. He had violaceous plaques with some desquamation and involvement of the palms and soles. His mucous membranes were clear.

Another biopsy from his trunk at this presentation showed vacuolar interface dermatitis with subdermal clefting and numerous necrotic keratinocytes, which could be consistent with either bullous lupus erythematosus or bullous erythema multiforme.

Direct immunofluorescence in this exacerbation was negative (previously it was positive), suggesting a diagnosis of Rowell's syndrome, which “very basically is erythema multiforme occurring in the setting of systemic lupus,” she said.

“Our patient's case … raises interesting questions about this congenital presentation of lupus. It is unusual for patients with typical neonatal lupus to develop SLE later on. This case makes one wonder if maybe that we should be questioning the sole role of maternal autoantibodies in this patient's case of congenital lupus. Perhaps he had some endogenous predisposition to develop lupus. This is the first patient we have observed with the clinical presentation of congenital, neonatal, and infantile lupus progressing to systemic lupus erythematosus as a teenager,” Dr. Maguiness said.

Discoid, hyperkeratotic, and hyperpig-mented plaques are seen on teen's face.

Biopsy shows interface dermatitis, necrotic keratinocytes, and subepidermal clefting. Photos courtesy Dr. Sheilagh Maguiness

NEW ORLEANS — Differential prophylactic aspirin use may contribute to racial disparities in stroke mortality, but does not appear to play a role in geographic disparities, according to findings from a cohort of patients in the ongoing Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Nearly 17,000 adults, aged 45 years and older, participated in this segment of the REGARDS study, which included a computer-assisted telephone survey that inquired about patterns of prophylactic aspirin use, a follow-up home visit for a brief medical evaluation including blood pressure measurement and blood sampling within 2 weeks of the survey. Follow-up telephone interviews were conducted every 6 months thereafter regarding events and changes in cognitive function, Virginia Howard, M.S.P.H., explained at International Stroke Conference 2008, sponsored by the American Stroke Association.

Patients who self-reported a history of heart disease, stroke, or aspirin use for pain relief, and patients in whom aspirin use could not be determined, were excluded from the analysis.

Overall, about 31% of participants used aspirin prophylactically, with slightly higher rates in the “stroke belt” of the Southeastern United States, compared with the rest of the country. Oversampling was done in the stroke belt because of the higher stroke rates in that region, explained Ms. Howard of the department of epidemiology at the University of Alabama at Birmingham.

Men were significantly more likely than women to use aspirin prophylactically, and white participants were significantly more likely than blacks to use aspirin prophylactically (see box). There was also a trend toward increasing use with advancing age, she said.

Aspirin use also was higher among those with higher income levels and among those with the highest educational levels.

There was little difference in usage patterns at other educational levels, however. Additionally, aspirin use was higher among smokers, particularly past smokers, and in those with hypertension, diabetes, and/or dyslipidemia.

The investigators also analyzed aspirin dosages, comparing use of 75 mg with use of 325 mg. No geographic or age differences were noted in regard to dose, but the use of the lower dose was more common in white participants, women, and those with higher socioeconomic status. No differences in dose were noted according to risk factors.

Overall, “we found that prophylactic aspirin use was remarkably common in this cohort,” Ms. Howard said.

“Related to our primary goals, we did find that prophylactic aspirin use was higher among whites than African Americans, so this raises the possibility that this could be contributing to racial disparities in stroke mortality.”

However, counter to the investigators' hypothesis, the disparity in prophylactic aspirin use does not appear to contribute to the excess mortality in the stroke belt, as use was more common in that region compared with the rest of the nation, she said.

Ms. Howard noted that she had no financial conflicts of interest. However, the lead investigator for this portion of the REGARD study, Dr. Stephen P. Glasser who is also with the university, was a clinical site principal investigator for a previous trial sponsored by Bayer Healthcare.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Differential prophylactic aspirin use may contribute to racial disparities in stroke mortality, but does not appear to play a role in geographic disparities, according to findings from a cohort of patients in the ongoing Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Nearly 17,000 adults, aged 45 years and older, participated in this segment of the REGARDS study, which included a computer-assisted telephone survey that inquired about patterns of prophylactic aspirin use, a follow-up home visit for a brief medical evaluation including blood pressure measurement and blood sampling within 2 weeks of the survey. Follow-up telephone interviews were conducted every 6 months thereafter regarding events and changes in cognitive function, Virginia Howard, M.S.P.H., explained at International Stroke Conference 2008, sponsored by the American Stroke Association.

Patients who self-reported a history of heart disease, stroke, or aspirin use for pain relief, and patients in whom aspirin use could not be determined, were excluded from the analysis.

Overall, about 31% of participants used aspirin prophylactically, with slightly higher rates in the “stroke belt” of the Southeastern United States, compared with the rest of the country. Oversampling was done in the stroke belt because of the higher stroke rates in that region, explained Ms. Howard of the department of epidemiology at the University of Alabama at Birmingham.

Men were significantly more likely than women to use aspirin prophylactically, and white participants were significantly more likely than blacks to use aspirin prophylactically (see box). There was also a trend toward increasing use with advancing age, she said.

Aspirin use also was higher among those with higher income levels and among those with the highest educational levels.

There was little difference in usage patterns at other educational levels, however. Additionally, aspirin use was higher among smokers, particularly past smokers, and in those with hypertension, diabetes, and/or dyslipidemia.

The investigators also analyzed aspirin dosages, comparing use of 75 mg with use of 325 mg. No geographic or age differences were noted in regard to dose, but the use of the lower dose was more common in white participants, women, and those with higher socioeconomic status. No differences in dose were noted according to risk factors.

Overall, “we found that prophylactic aspirin use was remarkably common in this cohort,” Ms. Howard said.

“Related to our primary goals, we did find that prophylactic aspirin use was higher among whites than African Americans, so this raises the possibility that this could be contributing to racial disparities in stroke mortality.”

However, counter to the investigators' hypothesis, the disparity in prophylactic aspirin use does not appear to contribute to the excess mortality in the stroke belt, as use was more common in that region compared with the rest of the nation, she said.

Ms. Howard noted that she had no financial conflicts of interest. However, the lead investigator for this portion of the REGARD study, Dr. Stephen P. Glasser who is also with the university, was a clinical site principal investigator for a previous trial sponsored by Bayer Healthcare.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Differential prophylactic aspirin use may contribute to racial disparities in stroke mortality, but does not appear to play a role in geographic disparities, according to findings from a cohort of patients in the ongoing Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Nearly 17,000 adults, aged 45 years and older, participated in this segment of the REGARDS study, which included a computer-assisted telephone survey that inquired about patterns of prophylactic aspirin use, a follow-up home visit for a brief medical evaluation including blood pressure measurement and blood sampling within 2 weeks of the survey. Follow-up telephone interviews were conducted every 6 months thereafter regarding events and changes in cognitive function, Virginia Howard, M.S.P.H., explained at International Stroke Conference 2008, sponsored by the American Stroke Association.

Patients who self-reported a history of heart disease, stroke, or aspirin use for pain relief, and patients in whom aspirin use could not be determined, were excluded from the analysis.

Overall, about 31% of participants used aspirin prophylactically, with slightly higher rates in the “stroke belt” of the Southeastern United States, compared with the rest of the country. Oversampling was done in the stroke belt because of the higher stroke rates in that region, explained Ms. Howard of the department of epidemiology at the University of Alabama at Birmingham.

Men were significantly more likely than women to use aspirin prophylactically, and white participants were significantly more likely than blacks to use aspirin prophylactically (see box). There was also a trend toward increasing use with advancing age, she said.

Aspirin use also was higher among those with higher income levels and among those with the highest educational levels.

There was little difference in usage patterns at other educational levels, however. Additionally, aspirin use was higher among smokers, particularly past smokers, and in those with hypertension, diabetes, and/or dyslipidemia.

The investigators also analyzed aspirin dosages, comparing use of 75 mg with use of 325 mg. No geographic or age differences were noted in regard to dose, but the use of the lower dose was more common in white participants, women, and those with higher socioeconomic status. No differences in dose were noted according to risk factors.

Overall, “we found that prophylactic aspirin use was remarkably common in this cohort,” Ms. Howard said.

“Related to our primary goals, we did find that prophylactic aspirin use was higher among whites than African Americans, so this raises the possibility that this could be contributing to racial disparities in stroke mortality.”

However, counter to the investigators' hypothesis, the disparity in prophylactic aspirin use does not appear to contribute to the excess mortality in the stroke belt, as use was more common in that region compared with the rest of the nation, she said.

Ms. Howard noted that she had no financial conflicts of interest. However, the lead investigator for this portion of the REGARD study, Dr. Stephen P. Glasser who is also with the university, was a clinical site principal investigator for a previous trial sponsored by Bayer Healthcare.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS – Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS–a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks–were included in the analysis.

The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10 mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Study participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

These preliminary results did not give enough information to determine the reason for the existence of the “stroke belt,” and Dr. Tsivgoulis didn't speculate on that in his presentation.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The finding of a linear and cross-sectional association between higher diastolic blood pressure and impaired cognitive status suggests that the careful monitoring and control of elevated blood pressure could contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

NEW ORLEANS – Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS–a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks–were included in the analysis.

The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10 mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Study participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

These preliminary results did not give enough information to determine the reason for the existence of the “stroke belt,” and Dr. Tsivgoulis didn't speculate on that in his presentation.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The finding of a linear and cross-sectional association between higher diastolic blood pressure and impaired cognitive status suggests that the careful monitoring and control of elevated blood pressure could contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

NEW ORLEANS – Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS–a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks–were included in the analysis.

The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10 mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Study participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

These preliminary results did not give enough information to determine the reason for the existence of the “stroke belt,” and Dr. Tsivgoulis didn't speculate on that in his presentation.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The finding of a linear and cross-sectional association between higher diastolic blood pressure and impaired cognitive status suggests that the careful monitoring and control of elevated blood pressure could contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

TAMPA — An experimental vaccine against human papillomavirus appeared to have therapeutic potential in a study of 20 women with HPV-16 positive vulvar intraepithelial neoplasia.

Treatment with the vaccine resulted in important T-cell responses in most patients after two vaccinations in the phase II study of women with histologically proven vulvar intraepithelial neoplasia (VIN). At 3 months, clinical efficacy was apparent in more than 50% of patients, and a complete response occurred in 25%, Dr. Gemma G. Kenter reported at the annual meeting of the Society of Gynecologic Oncologists.

The vaccine's design is based on long, overlapping peptides that cover the complete amino acid sequence of the HPV-16 E6 and E7 oncogenic proteins. Patients in the study were vaccinated four times at 3-week intervals. Interferon-gamma enzyme-linked immunospot (ELISPOT) analysis indicated that nearly all of the patients mounted a T-cell response to multiple regions of HPV-16 E6, and 75% did so against HPV-16 E7. These oncogenes represent the best targets for therapeutic vaccination, said Dr. Kenter of Leiden University (the Netherlands) Medical Center.

The natural HPV-specific E6 and E7 immune response is different in healthy patients than in infected patients, and proliferation assays in this study showed that the T-cell reactivity that was demonstrated is associated with the production of IFN-gamma and interleukin-5, similar to the cytokine profile of the HPV-16-specific memory T-cell responses observed in healthy individuals, Dr. Kenter explained.

A local immune response, namely infiltration of both the vaccination site and/or the VIN lesion by HPV-16-specific Th1 and Th2 cells, also was demonstrated.

The findings are encouraging, because HPV infection is common in young, sexually active individuals, and although most will clear the infection without developing clinical disease, some people experience a failure of the immune system in controlling the virus, and in these patients, malignancy can develop. The current study followed a phase I study in which the vaccine was found to elicit a strong HPV-16-specific T-cell response in 35 patients with end-stage cervical cancer, with no toxicity greater than grade 2 occurring.

"To our surprise, even in this patient group with end-stage disease, vaccination induced a strong type I immune response," Dr. Kenter said. A response to the E6 oncogene occurred in 90% of the patients, and a response to E7 occurred in 70%.

TAMPA — An experimental vaccine against human papillomavirus appeared to have therapeutic potential in a study of 20 women with HPV-16 positive vulvar intraepithelial neoplasia.

Treatment with the vaccine resulted in important T-cell responses in most patients after two vaccinations in the phase II study of women with histologically proven vulvar intraepithelial neoplasia (VIN). At 3 months, clinical efficacy was apparent in more than 50% of patients, and a complete response occurred in 25%, Dr. Gemma G. Kenter reported at the annual meeting of the Society of Gynecologic Oncologists.

The vaccine's design is based on long, overlapping peptides that cover the complete amino acid sequence of the HPV-16 E6 and E7 oncogenic proteins. Patients in the study were vaccinated four times at 3-week intervals. Interferon-gamma enzyme-linked immunospot (ELISPOT) analysis indicated that nearly all of the patients mounted a T-cell response to multiple regions of HPV-16 E6, and 75% did so against HPV-16 E7. These oncogenes represent the best targets for therapeutic vaccination, said Dr. Kenter of Leiden University (the Netherlands) Medical Center.

The natural HPV-specific E6 and E7 immune response is different in healthy patients than in infected patients, and proliferation assays in this study showed that the T-cell reactivity that was demonstrated is associated with the production of IFN-gamma and interleukin-5, similar to the cytokine profile of the HPV-16-specific memory T-cell responses observed in healthy individuals, Dr. Kenter explained.

A local immune response, namely infiltration of both the vaccination site and/or the VIN lesion by HPV-16-specific Th1 and Th2 cells, also was demonstrated.

The findings are encouraging, because HPV infection is common in young, sexually active individuals, and although most will clear the infection without developing clinical disease, some people experience a failure of the immune system in controlling the virus, and in these patients, malignancy can develop. The current study followed a phase I study in which the vaccine was found to elicit a strong HPV-16-specific T-cell response in 35 patients with end-stage cervical cancer, with no toxicity greater than grade 2 occurring.

"To our surprise, even in this patient group with end-stage disease, vaccination induced a strong type I immune response," Dr. Kenter said. A response to the E6 oncogene occurred in 90% of the patients, and a response to E7 occurred in 70%.

TAMPA — An experimental vaccine against human papillomavirus appeared to have therapeutic potential in a study of 20 women with HPV-16 positive vulvar intraepithelial neoplasia.

Treatment with the vaccine resulted in important T-cell responses in most patients after two vaccinations in the phase II study of women with histologically proven vulvar intraepithelial neoplasia (VIN). At 3 months, clinical efficacy was apparent in more than 50% of patients, and a complete response occurred in 25%, Dr. Gemma G. Kenter reported at the annual meeting of the Society of Gynecologic Oncologists.

The vaccine's design is based on long, overlapping peptides that cover the complete amino acid sequence of the HPV-16 E6 and E7 oncogenic proteins. Patients in the study were vaccinated four times at 3-week intervals. Interferon-gamma enzyme-linked immunospot (ELISPOT) analysis indicated that nearly all of the patients mounted a T-cell response to multiple regions of HPV-16 E6, and 75% did so against HPV-16 E7. These oncogenes represent the best targets for therapeutic vaccination, said Dr. Kenter of Leiden University (the Netherlands) Medical Center.

The natural HPV-specific E6 and E7 immune response is different in healthy patients than in infected patients, and proliferation assays in this study showed that the T-cell reactivity that was demonstrated is associated with the production of IFN-gamma and interleukin-5, similar to the cytokine profile of the HPV-16-specific memory T-cell responses observed in healthy individuals, Dr. Kenter explained.

A local immune response, namely infiltration of both the vaccination site and/or the VIN lesion by HPV-16-specific Th1 and Th2 cells, also was demonstrated.

The findings are encouraging, because HPV infection is common in young, sexually active individuals, and although most will clear the infection without developing clinical disease, some people experience a failure of the immune system in controlling the virus, and in these patients, malignancy can develop. The current study followed a phase I study in which the vaccine was found to elicit a strong HPV-16-specific T-cell response in 35 patients with end-stage cervical cancer, with no toxicity greater than grade 2 occurring.

"To our surprise, even in this patient group with end-stage disease, vaccination induced a strong type I immune response," Dr. Kenter said. A response to the E6 oncogene occurred in 90% of the patients, and a response to E7 occurred in 70%.

TAMPA — The Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of human papillomavirus, data from an extended follow-up study show.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase, Dr. Diane Harper reported at the annual meeting of the Society of Gynecologic Oncologists.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and 8-fold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

"This is an amazing result that bodes well for women's protection against cervical cancer," she commented in an interview, explaining that "there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers."

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18.

There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Efficacy was 72% against CIN2+ lesions independent of HPV status (5 vs. 17 cases in the vaccine and placebo groups, respectively). This is higher than the anticipated 50% based on the literature regarding the number of cases caused by the various types of HPV. Substantial cross-protection was maintained during the follow-up against incident infection with oncogenic HPV types 45 and 31, neither of which is covered by the vaccine.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide "a significant possible reduction in disease."

This is particularly noteworthy given the long follow-up, Dr. Harper said. That more than 90% of the original cohort was maintained for the follow-up study is "truly an amazing testament to the women who felt so strongly that these studies need to be done and are willing to continue to be followed for another 3 years up to 9.5 years," she added.

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said that she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honorarium from both companies for consultations and speaking fees.

'This is an amazing result that bodes wellfor women's protection against cervical cancer.' DR. HARPER

TAMPA — The Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of human papillomavirus, data from an extended follow-up study show.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase, Dr. Diane Harper reported at the annual meeting of the Society of Gynecologic Oncologists.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and 8-fold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

"This is an amazing result that bodes well for women's protection against cervical cancer," she commented in an interview, explaining that "there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers."

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18.

There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Efficacy was 72% against CIN2+ lesions independent of HPV status (5 vs. 17 cases in the vaccine and placebo groups, respectively). This is higher than the anticipated 50% based on the literature regarding the number of cases caused by the various types of HPV. Substantial cross-protection was maintained during the follow-up against incident infection with oncogenic HPV types 45 and 31, neither of which is covered by the vaccine.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide "a significant possible reduction in disease."

This is particularly noteworthy given the long follow-up, Dr. Harper said. That more than 90% of the original cohort was maintained for the follow-up study is "truly an amazing testament to the women who felt so strongly that these studies need to be done and are willing to continue to be followed for another 3 years up to 9.5 years," she added.

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said that she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honorarium from both companies for consultations and speaking fees.

'This is an amazing result that bodes wellfor women's protection against cervical cancer.' DR. HARPER

TAMPA — The Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of human papillomavirus, data from an extended follow-up study show.

The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 15–25 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase, Dr. Diane Harper reported at the annual meeting of the Society of Gynecologic Oncologists.

The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.

One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 years—with sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and 8-fold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.

"This is an amazing result that bodes well for women's protection against cervical cancer," she commented in an interview, explaining that "there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers."

The antibodies are abundant and waiting to neutralize an infection, she said.

Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18.

There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.

Efficacy was 72% against CIN2+ lesions independent of HPV status (5 vs. 17 cases in the vaccine and placebo groups, respectively). This is higher than the anticipated 50% based on the literature regarding the number of cases caused by the various types of HPV. Substantial cross-protection was maintained during the follow-up against incident infection with oncogenic HPV types 45 and 31, neither of which is covered by the vaccine.

Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide "a significant possible reduction in disease."

This is particularly noteworthy given the long follow-up, Dr. Harper said. That more than 90% of the original cohort was maintained for the follow-up study is "truly an amazing testament to the women who felt so strongly that these studies need to be done and are willing to continue to be followed for another 3 years up to 9.5 years," she added.

Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.

Dr. Harper said that she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarix—and for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honorarium from both companies for consultations and speaking fees.

'This is an amazing result that bodes wellfor women's protection against cervical cancer.' DR. HARPER

KISSIMMEE, FLA. — Body contouring using an external focused ultrasound device and a device that uses infrared light, bipolar radiofrequency energy, and mechanical massage is more effective than is ultrasound alone for treating localized fat, a study suggests. The combination approach also requires fewer treatments to achieve similar results, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Over 15 months, 198 patients—mostly women aged 24–52 years—were treated for localized fat, including 54 who were treated with UltraShape Ltd.'s Contour I ultrasound device and 144 who were treated with the Contour I in combination with Syneron Medical Ltd.'s VelaSmooth device.

Patients received up to three ultrasound treatment sessions targeting localized fat on the abdomen, flanks, and/or outer thighs—most patients received treatments on multiple areas during each session—followed immediately by a VelaSmooth treatment. VelaSmooth also was used weekly between ultrasound treatments, said Dr. Mazzi, who is in private practice in Verona, Italy.

During the study period, 1,082 ultrasound treatments (an average of 20 per patient) and 1,164 combination ultrasound and VelaSmooth treatments (8 per patient) were performed.

The outer thighs were the most commonly treated area (44% of treatments), followed by the abdomen (33% of treatments) and flanks (23% of patients), he noted.

An average circumference reduction of 4 cm per patient was noted after the last treatment with ultrasound plus VelaSmooth, versus 3 cm after the last treatment with ultrasound alone. Better results with fewer treatments were seen in the abdomen and flanks, whereas upper thighs with sclerotic fat tissue typically required more treatments to obtain satisfactory results, said Dr. Mazzi, who received honoraria from Syneron.

Side effects were comparable in both groups, with minor discomfort reported in 23% of patients; mild and transient erythema reported by 76%; and burning reported in 1%.

These treatments are indicated for the patient with a body mass index below 29 kg/m

The treatments are not intended for weight loss or for treating cellulite or skin laxity, although Dr. Mazzi believes the combined approach used in this study appears to result in improved skin tightening.

The Contour I device is used in Europe and Canada but is not yet approved for use in the United States. Approval by the Food and Drug Administration is anticipated later this year, he said.

A 45-year-old woman is shown before undergoing combination therapy to treat localized fat on her outer thighs (left). She is shown again after undergoing one treatment with ultrasound plus four treatments with VelaSmooth (right). Photos courtesy Dr. Luigi Mazzi

KISSIMMEE, FLA. — Body contouring using an external focused ultrasound device and a device that uses infrared light, bipolar radiofrequency energy, and mechanical massage is more effective than is ultrasound alone for treating localized fat, a study suggests. The combination approach also requires fewer treatments to achieve similar results, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Over 15 months, 198 patients—mostly women aged 24–52 years—were treated for localized fat, including 54 who were treated with UltraShape Ltd.'s Contour I ultrasound device and 144 who were treated with the Contour I in combination with Syneron Medical Ltd.'s VelaSmooth device.

Patients received up to three ultrasound treatment sessions targeting localized fat on the abdomen, flanks, and/or outer thighs—most patients received treatments on multiple areas during each session—followed immediately by a VelaSmooth treatment. VelaSmooth also was used weekly between ultrasound treatments, said Dr. Mazzi, who is in private practice in Verona, Italy.

During the study period, 1,082 ultrasound treatments (an average of 20 per patient) and 1,164 combination ultrasound and VelaSmooth treatments (8 per patient) were performed.

The outer thighs were the most commonly treated area (44% of treatments), followed by the abdomen (33% of treatments) and flanks (23% of patients), he noted.

An average circumference reduction of 4 cm per patient was noted after the last treatment with ultrasound plus VelaSmooth, versus 3 cm after the last treatment with ultrasound alone. Better results with fewer treatments were seen in the abdomen and flanks, whereas upper thighs with sclerotic fat tissue typically required more treatments to obtain satisfactory results, said Dr. Mazzi, who received honoraria from Syneron.

Side effects were comparable in both groups, with minor discomfort reported in 23% of patients; mild and transient erythema reported by 76%; and burning reported in 1%.

These treatments are indicated for the patient with a body mass index below 29 kg/m

The treatments are not intended for weight loss or for treating cellulite or skin laxity, although Dr. Mazzi believes the combined approach used in this study appears to result in improved skin tightening.

The Contour I device is used in Europe and Canada but is not yet approved for use in the United States. Approval by the Food and Drug Administration is anticipated later this year, he said.

A 45-year-old woman is shown before undergoing combination therapy to treat localized fat on her outer thighs (left). She is shown again after undergoing one treatment with ultrasound plus four treatments with VelaSmooth (right). Photos courtesy Dr. Luigi Mazzi

KISSIMMEE, FLA. — Body contouring using an external focused ultrasound device and a device that uses infrared light, bipolar radiofrequency energy, and mechanical massage is more effective than is ultrasound alone for treating localized fat, a study suggests. The combination approach also requires fewer treatments to achieve similar results, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Over 15 months, 198 patients—mostly women aged 24–52 years—were treated for localized fat, including 54 who were treated with UltraShape Ltd.'s Contour I ultrasound device and 144 who were treated with the Contour I in combination with Syneron Medical Ltd.'s VelaSmooth device.

Patients received up to three ultrasound treatment sessions targeting localized fat on the abdomen, flanks, and/or outer thighs—most patients received treatments on multiple areas during each session—followed immediately by a VelaSmooth treatment. VelaSmooth also was used weekly between ultrasound treatments, said Dr. Mazzi, who is in private practice in Verona, Italy.

During the study period, 1,082 ultrasound treatments (an average of 20 per patient) and 1,164 combination ultrasound and VelaSmooth treatments (8 per patient) were performed.

The outer thighs were the most commonly treated area (44% of treatments), followed by the abdomen (33% of treatments) and flanks (23% of patients), he noted.

An average circumference reduction of 4 cm per patient was noted after the last treatment with ultrasound plus VelaSmooth, versus 3 cm after the last treatment with ultrasound alone. Better results with fewer treatments were seen in the abdomen and flanks, whereas upper thighs with sclerotic fat tissue typically required more treatments to obtain satisfactory results, said Dr. Mazzi, who received honoraria from Syneron.

Side effects were comparable in both groups, with minor discomfort reported in 23% of patients; mild and transient erythema reported by 76%; and burning reported in 1%.

These treatments are indicated for the patient with a body mass index below 29 kg/m

The treatments are not intended for weight loss or for treating cellulite or skin laxity, although Dr. Mazzi believes the combined approach used in this study appears to result in improved skin tightening.

The Contour I device is used in Europe and Canada but is not yet approved for use in the United States. Approval by the Food and Drug Administration is anticipated later this year, he said.

A 45-year-old woman is shown before undergoing combination therapy to treat localized fat on her outer thighs (left). She is shown again after undergoing one treatment with ultrasound plus four treatments with VelaSmooth (right). Photos courtesy Dr. Luigi Mazzi

KISSIMMEE, FLA. — Laser lipolysis using a 1,064-nm Nd:YAG laser has been shown to be effective—and is safer than traditional liposuction—according to the results of two studies.

Few complications have occurred with SmartLipo laser lipolysis (Cynosure Inc.), a fat-melting and skin-tightening device that was approved by the Food and Drug Administration in 2006 for the treatment of localized fat deposits, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Dr. Mazzi of Verona, Italy, reported his 4-year experience using the laser on 386 patients aged 18–55.

The patients—mostly women (82%)—underwent an average of three treatments in a variety of areas, including the arms, flanks, abdomen, inner and outer thighs, and inner knees.

Only two serious complications occurred, both superficial burns. Swelling and ecchymosis occurred often; they are considered normal after treatment, however, and regress within 8–10 days.

Dr. Mazzi said that in addition to localized fat, larger areas of adiposity can be treated using SmartLipo, but suction of the emulsified fat tissue in these cases is imperative, and the safety outcomes when suction is used are similar to those seen with traditional liposuction.

Dr. Mazzi said that he had no financial interest related to the SmartLipo technology.

SmartLipo is indeed exceedingly safe, agreed Dr. Bruce E. Katz, who reported on his experience using the technology in patients aged 17–77 years who underwent SmartLipo laser lipolysis over an 18-month period.

The review showed that 3 of the 537 patients experienced minor skin burns, all of which healed with no permanent sequelae, for a complication rate of less than 1%, said Dr. Katz of Juva Skin & Laser Center, New York. The complication rate in this review of cases was much lower than that reported in the literature for traditional liposuction.

Only 3% of patients underwent touch-up procedures, compared with about 10%–12% of those undergoing traditional liposuction, noted Dr. Katz. "Most importantly, there were no major complications."

Most patients underwent treatment of the abdomen, hips, and/or thighs, said Dr. Katz, who receives consulting fees from El.En Engineering, a major Cynosure shareholder.

The SmartLipo device uses a small, 1-mm cannula, which causes less trauma than is associated with traditional liposuction. A 300-mcm optic fiber is inserted into the cannula and energy is then delivered using a 150-microsecond pulse duration.

Other advantages of SmartLipo include the fat emulsion and skin tightening that occur with the procedure, which is indicated for small areas of local adiposities, and in areas where liposuction would be indicated, but where skin laxity might be worsened by the fat removal.

A number of studies have demonstrated efficacy, ease of use, and other benefits with the minimally invasive SmartLipo procedure, including reduced trauma to tissues, less blood loss, and greater postoperative comfort, compared with traditional liposuction, said Dr. Katz.

A patient is shown before laser lipolysis therapy (left) and 8 months after undergoing two separate treatments with the SmartLipo device (right). Photos courtesy Dr. Luigi Mazzi

KISSIMMEE, FLA. — Laser lipolysis using a 1,064-nm Nd:YAG laser has been shown to be effective—and is safer than traditional liposuction—according to the results of two studies.

Few complications have occurred with SmartLipo laser lipolysis (Cynosure Inc.), a fat-melting and skin-tightening device that was approved by the Food and Drug Administration in 2006 for the treatment of localized fat deposits, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Dr. Mazzi of Verona, Italy, reported his 4-year experience using the laser on 386 patients aged 18–55.

The patients—mostly women (82%)—underwent an average of three treatments in a variety of areas, including the arms, flanks, abdomen, inner and outer thighs, and inner knees.

Only two serious complications occurred, both superficial burns. Swelling and ecchymosis occurred often; they are considered normal after treatment, however, and regress within 8–10 days.

Dr. Mazzi said that in addition to localized fat, larger areas of adiposity can be treated using SmartLipo, but suction of the emulsified fat tissue in these cases is imperative, and the safety outcomes when suction is used are similar to those seen with traditional liposuction.

Dr. Mazzi said that he had no financial interest related to the SmartLipo technology.

SmartLipo is indeed exceedingly safe, agreed Dr. Bruce E. Katz, who reported on his experience using the technology in patients aged 17–77 years who underwent SmartLipo laser lipolysis over an 18-month period.

The review showed that 3 of the 537 patients experienced minor skin burns, all of which healed with no permanent sequelae, for a complication rate of less than 1%, said Dr. Katz of Juva Skin & Laser Center, New York. The complication rate in this review of cases was much lower than that reported in the literature for traditional liposuction.

Only 3% of patients underwent touch-up procedures, compared with about 10%–12% of those undergoing traditional liposuction, noted Dr. Katz. "Most importantly, there were no major complications."

Most patients underwent treatment of the abdomen, hips, and/or thighs, said Dr. Katz, who receives consulting fees from El.En Engineering, a major Cynosure shareholder.

The SmartLipo device uses a small, 1-mm cannula, which causes less trauma than is associated with traditional liposuction. A 300-mcm optic fiber is inserted into the cannula and energy is then delivered using a 150-microsecond pulse duration.

Other advantages of SmartLipo include the fat emulsion and skin tightening that occur with the procedure, which is indicated for small areas of local adiposities, and in areas where liposuction would be indicated, but where skin laxity might be worsened by the fat removal.

A number of studies have demonstrated efficacy, ease of use, and other benefits with the minimally invasive SmartLipo procedure, including reduced trauma to tissues, less blood loss, and greater postoperative comfort, compared with traditional liposuction, said Dr. Katz.

A patient is shown before laser lipolysis therapy (left) and 8 months after undergoing two separate treatments with the SmartLipo device (right). Photos courtesy Dr. Luigi Mazzi

KISSIMMEE, FLA. — Laser lipolysis using a 1,064-nm Nd:YAG laser has been shown to be effective—and is safer than traditional liposuction—according to the results of two studies.

Few complications have occurred with SmartLipo laser lipolysis (Cynosure Inc.), a fat-melting and skin-tightening device that was approved by the Food and Drug Administration in 2006 for the treatment of localized fat deposits, Dr. Luigi Mazzi reported at the annual meeting of the American Society for Laser Medicine and Surgery.

Dr. Mazzi of Verona, Italy, reported his 4-year experience using the laser on 386 patients aged 18–55.

The patients—mostly women (82%)—underwent an average of three treatments in a variety of areas, including the arms, flanks, abdomen, inner and outer thighs, and inner knees.

Only two serious complications occurred, both superficial burns. Swelling and ecchymosis occurred often; they are considered normal after treatment, however, and regress within 8–10 days.

Dr. Mazzi said that in addition to localized fat, larger areas of adiposity can be treated using SmartLipo, but suction of the emulsified fat tissue in these cases is imperative, and the safety outcomes when suction is used are similar to those seen with traditional liposuction.

Dr. Mazzi said that he had no financial interest related to the SmartLipo technology.

SmartLipo is indeed exceedingly safe, agreed Dr. Bruce E. Katz, who reported on his experience using the technology in patients aged 17–77 years who underwent SmartLipo laser lipolysis over an 18-month period.

The review showed that 3 of the 537 patients experienced minor skin burns, all of which healed with no permanent sequelae, for a complication rate of less than 1%, said Dr. Katz of Juva Skin & Laser Center, New York. The complication rate in this review of cases was much lower than that reported in the literature for traditional liposuction.

Only 3% of patients underwent touch-up procedures, compared with about 10%–12% of those undergoing traditional liposuction, noted Dr. Katz. "Most importantly, there were no major complications."

Most patients underwent treatment of the abdomen, hips, and/or thighs, said Dr. Katz, who receives consulting fees from El.En Engineering, a major Cynosure shareholder.

The SmartLipo device uses a small, 1-mm cannula, which causes less trauma than is associated with traditional liposuction. A 300-mcm optic fiber is inserted into the cannula and energy is then delivered using a 150-microsecond pulse duration.

Other advantages of SmartLipo include the fat emulsion and skin tightening that occur with the procedure, which is indicated for small areas of local adiposities, and in areas where liposuction would be indicated, but where skin laxity might be worsened by the fat removal.

A number of studies have demonstrated efficacy, ease of use, and other benefits with the minimally invasive SmartLipo procedure, including reduced trauma to tissues, less blood loss, and greater postoperative comfort, compared with traditional liposuction, said Dr. Katz.

A patient is shown before laser lipolysis therapy (left) and 8 months after undergoing two separate treatments with the SmartLipo device (right). Photos courtesy Dr. Luigi Mazzi

NEW ORLEANS — Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS—a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks—were included in the analysis. The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10-mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The findings suggest that careful monitoring and control of elevated blood pressure may contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

NEW ORLEANS — Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS—a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks—were included in the analysis. The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10-mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The findings suggest that careful monitoring and control of elevated blood pressure may contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

NEW ORLEANS — Increased diastolic blood pressure levels are associated with cognitive impairment, findings from the Reasons for Geographic and Racial Differences in Stroke study suggest.

More than 27,800 participants from REGARDS—a long-term, ongoing study designed to investigate the reasons why stroke-related mortality is more common in portions of the southeastern United States (the “stroke belt”) and among blacks—were included in the analysis. The patients were evaluated in an effort to identify associations between blood pressure indices and cognitive function, as well as any potential interactions between blood pressure indices and age in cognitive function, and any possible racial differences in the relationship between blood pressure and cognition, Dr. Georgios Tsivgoulis, lead author in this portion of the study, reported at the International Stroke Conference 2008.

Findings from previous studies have been conflicting in regard to such interactions, but in this very large cohort of patients, the relationship between diastolic blood pressure levels and cognitive impairment persisted even after adjusting for a host of demographic characteristics, environmental factors, vascular risk factors, health behaviors, and depressive symptoms (odds ratio, 1.08 per 10-mm Hg change for cognitive impairment with increased diastolic blood pressure), said Dr. Tsivgoulis of the University of Alabama at Birmingham.

No interactions were seen between blood pressure and age in impaired cognitive function, nor were racial differences noted in the associations between blood pressure and cognitive status, he said at the conference, which was sponsored by the American Stroke Association.

Participants were at least 45 years of age (mean age, 66 years in the current cohort), and lived in various areas across the United States, with oversampling in the stroke belt. Whites and blacks, as well as men and women, were equally represented.

Cognitive status was assessed using the 6-item screen derived from the Mini-Mental State Examination. Patients with a score of 4 or less were considered to have cognitive impairment. Cognitive status was validated against other cognitive measures for the diagnosis of dementia, and depression was assessed using the Center for Epidemiologic Studies Depression 4-item scale.

The findings suggest that careful monitoring and control of elevated blood pressure may contribute to the preservation of cognitive function, Dr. Tsivgoulis concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke.

NEW ORLEANS — A novel clot removal device appears safe and effective for revascularizing patients with acute ischemic stroke secondary to large vessel occlusion, according to results of a multicenter study of 125 acute stroke patients.

Of those patients in a prospective, single-arm trial designed to assess the safety and efficacy of the Penumbra System (Penumbra Inc.), 82% were successfully revascularized. Successful revascularization—the primary end point in the study—was defined as a change from a Thrombosis in Myocardial Infarction (TIMI) risk score of 0 or 1 to a score of 2 or 3 following treatment with the device, Dr. Cameron McDougall reported at International Stroke Conference 2008.

The Penumbra System comprises multiple device options, including a reperfusion catheter for aspirating clots, a separator designed to allow the reperfusion catheter to aspirate continually, and a thrombus removal ring designed to grasp and capture calcified clots that are not aspirated. The operator selects the appropriate device platform based on the nature of the thrombotic occlusion and the angio-architecture of the target vessel.

In the current trial (the Penumbra Stroke Trial), TIMI 2 or 3 revascularization scores were achieved in 81% of patients using only the aspiration device platform; only one patient required use of the extraction (clot grasping) device, for a revascularization rate of 82% when both were used, Dr. McDougall of Barrow Neurological Institute, Phoenix, reported.

A favorable outcome, defined as either a 4-point improvement on the National Institutes of Health Stroke Scale (NIHSS) at discharge, a 10-point improvement on the NIHSS (or a score of 0–1) at discharge, or a 90-day modified Rankin Scale score of 2 or less, occurred in 58%, 27%, and 25% of patients, respectively. Better outcomes occurred in those with a baseline NIHSS score of 20 or less, compared with those with higher scores (see graphic). All-cause mortality was 26% at 30 days, and 33% at 90 days.

The trend for improved outcome with revascularization was consistent across all neurologic functional measures, noted Dr. McDougall, who had no financial or other relationships to disclose.

The device also proved safe, he said at the conference, which was sponsored by the American Stroke Association.

Four procedural serious adverse events were reported in four patients, but none were attributed to the device, and no device malfunctions or breakage occurred. A total of 35 patients (28%) had intracranial hemorrhage at 24 hours, including 14 (11%) who were symptomatic.

Patients in the trial had a mean age of 63 years, baseline NIHSS scores of at least 8, and presented within 8 hours of symptom onset. Those who presented within 3 hours of symptom onset had to be ineligible for, or refractory to recombinant tissue-type plasminogen activator (rTPA) therapy to be enrolled.

The target vessel was the internal carotid artery in 18% of patients, the middle cerebral artery in 70%, the vertebrobasilar artery in 9%, and another vessel in 3%.

The median time to arterial puncture from the time of symptom onset was 4 hours, and the median time to revascularization was 45 minutes.

Serious adverse events that occurred in study participants included two perforations, and two intracerebral hemorrhages, including one that was a result of perforation, for a serious adverse event rate of 3%.

Compared with historic controls from a trial of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) clot retrieval device—as established prior to the Penumbra Stroke trial—the outcomes with the Penumbra System were superior (82% vs. 48% recanalization rates).

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — A novel clot removal device appears safe and effective for revascularizing patients with acute ischemic stroke secondary to large vessel occlusion, according to results of a multicenter study of 125 acute stroke patients.

Of those patients in a prospective, single-arm trial designed to assess the safety and efficacy of the Penumbra System (Penumbra Inc.), 82% were successfully revascularized. Successful revascularization—the primary end point in the study—was defined as a change from a Thrombosis in Myocardial Infarction (TIMI) risk score of 0 or 1 to a score of 2 or 3 following treatment with the device, Dr. Cameron McDougall reported at International Stroke Conference 2008.

The Penumbra System comprises multiple device options, including a reperfusion catheter for aspirating clots, a separator designed to allow the reperfusion catheter to aspirate continually, and a thrombus removal ring designed to grasp and capture calcified clots that are not aspirated. The operator selects the appropriate device platform based on the nature of the thrombotic occlusion and the angio-architecture of the target vessel.

In the current trial (the Penumbra Stroke Trial), TIMI 2 or 3 revascularization scores were achieved in 81% of patients using only the aspiration device platform; only one patient required use of the extraction (clot grasping) device, for a revascularization rate of 82% when both were used, Dr. McDougall of Barrow Neurological Institute, Phoenix, reported.

A favorable outcome, defined as either a 4-point improvement on the National Institutes of Health Stroke Scale (NIHSS) at discharge, a 10-point improvement on the NIHSS (or a score of 0–1) at discharge, or a 90-day modified Rankin Scale score of 2 or less, occurred in 58%, 27%, and 25% of patients, respectively. Better outcomes occurred in those with a baseline NIHSS score of 20 or less, compared with those with higher scores (see graphic). All-cause mortality was 26% at 30 days, and 33% at 90 days.

The trend for improved outcome with revascularization was consistent across all neurologic functional measures, noted Dr. McDougall, who had no financial or other relationships to disclose.

The device also proved safe, he said at the conference, which was sponsored by the American Stroke Association.

Four procedural serious adverse events were reported in four patients, but none were attributed to the device, and no device malfunctions or breakage occurred. A total of 35 patients (28%) had intracranial hemorrhage at 24 hours, including 14 (11%) who were symptomatic.

Patients in the trial had a mean age of 63 years, baseline NIHSS scores of at least 8, and presented within 8 hours of symptom onset. Those who presented within 3 hours of symptom onset had to be ineligible for, or refractory to recombinant tissue-type plasminogen activator (rTPA) therapy to be enrolled.

The target vessel was the internal carotid artery in 18% of patients, the middle cerebral artery in 70%, the vertebrobasilar artery in 9%, and another vessel in 3%.

The median time to arterial puncture from the time of symptom onset was 4 hours, and the median time to revascularization was 45 minutes.

Serious adverse events that occurred in study participants included two perforations, and two intracerebral hemorrhages, including one that was a result of perforation, for a serious adverse event rate of 3%.

Compared with historic controls from a trial of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) clot retrieval device—as established prior to the Penumbra Stroke trial—the outcomes with the Penumbra System were superior (82% vs. 48% recanalization rates).

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — A novel clot removal device appears safe and effective for revascularizing patients with acute ischemic stroke secondary to large vessel occlusion, according to results of a multicenter study of 125 acute stroke patients.

Of those patients in a prospective, single-arm trial designed to assess the safety and efficacy of the Penumbra System (Penumbra Inc.), 82% were successfully revascularized. Successful revascularization—the primary end point in the study—was defined as a change from a Thrombosis in Myocardial Infarction (TIMI) risk score of 0 or 1 to a score of 2 or 3 following treatment with the device, Dr. Cameron McDougall reported at International Stroke Conference 2008.

The Penumbra System comprises multiple device options, including a reperfusion catheter for aspirating clots, a separator designed to allow the reperfusion catheter to aspirate continually, and a thrombus removal ring designed to grasp and capture calcified clots that are not aspirated. The operator selects the appropriate device platform based on the nature of the thrombotic occlusion and the angio-architecture of the target vessel.

In the current trial (the Penumbra Stroke Trial), TIMI 2 or 3 revascularization scores were achieved in 81% of patients using only the aspiration device platform; only one patient required use of the extraction (clot grasping) device, for a revascularization rate of 82% when both were used, Dr. McDougall of Barrow Neurological Institute, Phoenix, reported.

A favorable outcome, defined as either a 4-point improvement on the National Institutes of Health Stroke Scale (NIHSS) at discharge, a 10-point improvement on the NIHSS (or a score of 0–1) at discharge, or a 90-day modified Rankin Scale score of 2 or less, occurred in 58%, 27%, and 25% of patients, respectively. Better outcomes occurred in those with a baseline NIHSS score of 20 or less, compared with those with higher scores (see graphic). All-cause mortality was 26% at 30 days, and 33% at 90 days.

The trend for improved outcome with revascularization was consistent across all neurologic functional measures, noted Dr. McDougall, who had no financial or other relationships to disclose.

The device also proved safe, he said at the conference, which was sponsored by the American Stroke Association.

Four procedural serious adverse events were reported in four patients, but none were attributed to the device, and no device malfunctions or breakage occurred. A total of 35 patients (28%) had intracranial hemorrhage at 24 hours, including 14 (11%) who were symptomatic.

Patients in the trial had a mean age of 63 years, baseline NIHSS scores of at least 8, and presented within 8 hours of symptom onset. Those who presented within 3 hours of symptom onset had to be ineligible for, or refractory to recombinant tissue-type plasminogen activator (rTPA) therapy to be enrolled.

The target vessel was the internal carotid artery in 18% of patients, the middle cerebral artery in 70%, the vertebrobasilar artery in 9%, and another vessel in 3%.

The median time to arterial puncture from the time of symptom onset was 4 hours, and the median time to revascularization was 45 minutes.

Serious adverse events that occurred in study participants included two perforations, and two intracerebral hemorrhages, including one that was a result of perforation, for a serious adverse event rate of 3%.

Compared with historic controls from a trial of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) clot retrieval device—as established prior to the Penumbra Stroke trial—the outcomes with the Penumbra System were superior (82% vs. 48% recanalization rates).

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS – Donepezil had no effect on cognitive impairment in a recent study of patients with vascular dementia, but the acetylcholinesterase inhibitor was associated with significant improvement on several measures of executive function, Dr. Martin Dichgans reported at International Stroke Conference 2008.

Cholinergic deficits might contribute to cognitive impairment in vascular dementia, and donepezil has been shown to improve measures of functioning, but because most trials of the drug include patients with Alzheimer's disease, it is difficult to determine whether the effects of the drug result from improvements in cognition or improvement in the Alzheimer's disease.

For the current study, 168 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) were included in the randomized double-blind study, which was a phase II proof of concept study. CADASIL is an early-onset form of subcortical ischemic vascular dementia that is unlikely to overlap with Alzheimer's disease, making it a condition well suited for testing the effects of donepezil on cognitive functioning, said Dr. Dichgans of Ludwig-Maximilians University, Munich.

Patients received 5 mg of donepezil or placebo daily for the first 6 weeks of the 18-week trial, then 10 mg daily thereafter; the primary end point was a change from baseline in Vascular-Alzheimer's Disease Assessment Scale-Cognitive subscale (V-ADAS-cog) score, said Dr. Dichgans, who serves as a consultant for Eisai Co., which makes donepezil and sponsored the study.

There was no statistically significant difference between the treatment and placebo groups in regard to the change from baseline V-ADAS-cog scores, but a significant difference was noted between the groups on Trail Making Test part A (TMT A) time and Trail Making Test part B (TMT B) time, which assess the time required to perform specific tasks, and on the Executive Interview (EXIT25), which assesses executive cognitive function. (See box.)

A trend toward improvement on the clock drawing tests CLOX 1 and CLOX 2 scores–which measure executive cognitive function deficits and posterior cortical impairment, respectively–was also seen in the treatment group, compared with the placebo group, Dr. Dichgans said at the conference, which was sponsored by the American Stroke Association.

For the treatment group, CLOX1 score improved from baseline by 0.76, compared with 0.09 for placebo. For the CLOX2 group, treated patients' score improved by 0.52 from baseline, versus 0.05 for patients on placebo.

Clinical relevance of findings on processing speed is unknown, he noted.

Patients in the study had a mean age of 55 years. Inclusion criteria included a baseline score of 10-27 on the Mini-Mental State Exam or a TMT B score that was 1.5 standard deviations below the mean after adjusting for age and education.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS – Donepezil had no effect on cognitive impairment in a recent study of patients with vascular dementia, but the acetylcholinesterase inhibitor was associated with significant improvement on several measures of executive function, Dr. Martin Dichgans reported at International Stroke Conference 2008.

Cholinergic deficits might contribute to cognitive impairment in vascular dementia, and donepezil has been shown to improve measures of functioning, but because most trials of the drug include patients with Alzheimer's disease, it is difficult to determine whether the effects of the drug result from improvements in cognition or improvement in the Alzheimer's disease.

For the current study, 168 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) were included in the randomized double-blind study, which was a phase II proof of concept study. CADASIL is an early-onset form of subcortical ischemic vascular dementia that is unlikely to overlap with Alzheimer's disease, making it a condition well suited for testing the effects of donepezil on cognitive functioning, said Dr. Dichgans of Ludwig-Maximilians University, Munich.

Patients received 5 mg of donepezil or placebo daily for the first 6 weeks of the 18-week trial, then 10 mg daily thereafter; the primary end point was a change from baseline in Vascular-Alzheimer's Disease Assessment Scale-Cognitive subscale (V-ADAS-cog) score, said Dr. Dichgans, who serves as a consultant for Eisai Co., which makes donepezil and sponsored the study.

There was no statistically significant difference between the treatment and placebo groups in regard to the change from baseline V-ADAS-cog scores, but a significant difference was noted between the groups on Trail Making Test part A (TMT A) time and Trail Making Test part B (TMT B) time, which assess the time required to perform specific tasks, and on the Executive Interview (EXIT25), which assesses executive cognitive function. (See box.)

A trend toward improvement on the clock drawing tests CLOX 1 and CLOX 2 scores–which measure executive cognitive function deficits and posterior cortical impairment, respectively–was also seen in the treatment group, compared with the placebo group, Dr. Dichgans said at the conference, which was sponsored by the American Stroke Association.

For the treatment group, CLOX1 score improved from baseline by 0.76, compared with 0.09 for placebo. For the CLOX2 group, treated patients' score improved by 0.52 from baseline, versus 0.05 for patients on placebo.

Clinical relevance of findings on processing speed is unknown, he noted.

Patients in the study had a mean age of 55 years. Inclusion criteria included a baseline score of 10-27 on the Mini-Mental State Exam or a TMT B score that was 1.5 standard deviations below the mean after adjusting for age and education.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS – Donepezil had no effect on cognitive impairment in a recent study of patients with vascular dementia, but the acetylcholinesterase inhibitor was associated with significant improvement on several measures of executive function, Dr. Martin Dichgans reported at International Stroke Conference 2008.

Cholinergic deficits might contribute to cognitive impairment in vascular dementia, and donepezil has been shown to improve measures of functioning, but because most trials of the drug include patients with Alzheimer's disease, it is difficult to determine whether the effects of the drug result from improvements in cognition or improvement in the Alzheimer's disease.

For the current study, 168 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) were included in the randomized double-blind study, which was a phase II proof of concept study. CADASIL is an early-onset form of subcortical ischemic vascular dementia that is unlikely to overlap with Alzheimer's disease, making it a condition well suited for testing the effects of donepezil on cognitive functioning, said Dr. Dichgans of Ludwig-Maximilians University, Munich.

Patients received 5 mg of donepezil or placebo daily for the first 6 weeks of the 18-week trial, then 10 mg daily thereafter; the primary end point was a change from baseline in Vascular-Alzheimer's Disease Assessment Scale-Cognitive subscale (V-ADAS-cog) score, said Dr. Dichgans, who serves as a consultant for Eisai Co., which makes donepezil and sponsored the study.

There was no statistically significant difference between the treatment and placebo groups in regard to the change from baseline V-ADAS-cog scores, but a significant difference was noted between the groups on Trail Making Test part A (TMT A) time and Trail Making Test part B (TMT B) time, which assess the time required to perform specific tasks, and on the Executive Interview (EXIT25), which assesses executive cognitive function. (See box.)

A trend toward improvement on the clock drawing tests CLOX 1 and CLOX 2 scores–which measure executive cognitive function deficits and posterior cortical impairment, respectively–was also seen in the treatment group, compared with the placebo group, Dr. Dichgans said at the conference, which was sponsored by the American Stroke Association.

For the treatment group, CLOX1 score improved from baseline by 0.76, compared with 0.09 for placebo. For the CLOX2 group, treated patients' score improved by 0.52 from baseline, versus 0.05 for patients on placebo.

Clinical relevance of findings on processing speed is unknown, he noted.

Patients in the study had a mean age of 55 years. Inclusion criteria included a baseline score of 10-27 on the Mini-Mental State Exam or a TMT B score that was 1.5 standard deviations below the mean after adjusting for age and education.

ELSEVIER GLOBAL MEDICAL NEWS