Kerri Wachter

Clinical MRI studies are typically performed with 1.5-tesla (T) magnets, though the use of 3-T systems is becoming more common. The use of ultrahigh-field-strength MRI—using 7-T magnets—remains largely the domain of major research facilities such as New York University.

Dr. Yulin Ge, a radiologist at New York University, New York, and his colleagues have been using 7-T MRI to further their understanding of the pathophysiology of multiple sclerosis.

There are two main advantages to high-field MRI over imaging with conventional field-strength magnets. The higher signal intensity-to-noise ratio (SNR) that can be achieved with a stronger magnet strength allows for greater resolution, which in turn can improve the detection of lesions. Lesion counts may be 45% greater using a 4T system with better appreciation of tissue heterogeneity within lesions as compared with a 1.5-T system.

Separately, higher field strength also boosts susceptibility effects. Magnetic susceptibility is the degree of magnetization of a material in response to an applied magnetic field. Oxyhemoglobin in arterial blood has no substantial magnetic properties, but deoxyhemoglobin, which is present in the draining veins after the oxygen has been unloaded in the tissues, is strongly paramagnetic. It can thus serve as an intrinsic paramagnetic contrast agent, the effect of which is increased with greater field strength. This in turn improves the examination of microscopic venous structures, brain iron, and microbleeds. “So venous structures can be shown very well on high-field MRI,” Dr. Ge said in an interview.

The researchers have been able to directly see small vascular abnormalities—mainly small venous structures—at a very early stage of MS. “These findings have never been shown on conventional MR,” he said. High-field MRI detects these changes before the blood-brain barrier breakdown that can be seen on conventional MRI.

The MS lesions appear to be centered on a small venule. “We can see the abnormal signals on and around the venous wall,” Dr. Ge said. “And the lesion developed along the veins—along the venous course in the initial stage of development can be clearly seen on 7T MRI.” These findings may be direct in vivo evidence of the vascular pathogenesis of lesions, he added. While it takes only 6 minutes to perform such susceptibility-sensitive imaging, slices are 2 mm thick with pixel resolution of 0.2x0.2 mm

These vascular abnormalities are “not seen in one or two lesions but in many lesions,” he said (as shown in image A). The number of lesions with vascular abnormalities that can be detected “gives you a very important indication of disease activity beyond the resolution of conventional MRI.”

Gadolinium-enhancing lesions currently are considered the first detectable MR abnormalities in MS patients. However, the fact that vascular abnormalities detected using ultrahigh-field MRI can be seen even earlier “has important implications for treatment,” said Dr. Ge.

High-field-strength MRI might allow physicians to track the early disease activity and the effectiveness of treatments. This is particularly important now that disease-modifying therapies are available.

The immunomodulatory drugs—interferon β-1a IM (Avonex), interferon β-1b SC (Betaseron) glatiramer acetate SC (Copaxone), or interferon β-1a SC (Rebif) are approved for and are currently used in the United States as first-line therapies for MS to prevent relapses or disease progression.

Newer compounds approved by the Food and Drug Administration for use in MS include mitoxantrone (Novantrone) and natalizumab (Tysabri). Last year, natalizumab was reintroduced for the treatment of relapsing forms of MS with a black box warning about the risk of progressive multifocal leukoencephalopathy associated with treatment. The drug had previously been voluntarily suspended from the market following the development of PML in three patients treated with the drug (two for MS and one for Crohn's disease).

Ultra-high-field MRI shows an intimate relationship between lesions and centered small veins (arrows), suggesting a primarily vascular pathogenesis of MS lesions. Photos courtesy Dr. Yulin Ge

Clinical MRI studies are typically performed with 1.5-tesla (T) magnets, though the use of 3-T systems is becoming more common. The use of ultrahigh-field-strength MRI—using 7-T magnets—remains largely the domain of major research facilities such as New York University.

Dr. Yulin Ge, a radiologist at New York University, New York, and his colleagues have been using 7-T MRI to further their understanding of the pathophysiology of multiple sclerosis.

There are two main advantages to high-field MRI over imaging with conventional field-strength magnets. The higher signal intensity-to-noise ratio (SNR) that can be achieved with a stronger magnet strength allows for greater resolution, which in turn can improve the detection of lesions. Lesion counts may be 45% greater using a 4T system with better appreciation of tissue heterogeneity within lesions as compared with a 1.5-T system.

Separately, higher field strength also boosts susceptibility effects. Magnetic susceptibility is the degree of magnetization of a material in response to an applied magnetic field. Oxyhemoglobin in arterial blood has no substantial magnetic properties, but deoxyhemoglobin, which is present in the draining veins after the oxygen has been unloaded in the tissues, is strongly paramagnetic. It can thus serve as an intrinsic paramagnetic contrast agent, the effect of which is increased with greater field strength. This in turn improves the examination of microscopic venous structures, brain iron, and microbleeds. “So venous structures can be shown very well on high-field MRI,” Dr. Ge said in an interview.

The researchers have been able to directly see small vascular abnormalities—mainly small venous structures—at a very early stage of MS. “These findings have never been shown on conventional MR,” he said. High-field MRI detects these changes before the blood-brain barrier breakdown that can be seen on conventional MRI.

The MS lesions appear to be centered on a small venule. “We can see the abnormal signals on and around the venous wall,” Dr. Ge said. “And the lesion developed along the veins—along the venous course in the initial stage of development can be clearly seen on 7T MRI.” These findings may be direct in vivo evidence of the vascular pathogenesis of lesions, he added. While it takes only 6 minutes to perform such susceptibility-sensitive imaging, slices are 2 mm thick with pixel resolution of 0.2x0.2 mm

These vascular abnormalities are “not seen in one or two lesions but in many lesions,” he said (as shown in image A). The number of lesions with vascular abnormalities that can be detected “gives you a very important indication of disease activity beyond the resolution of conventional MRI.”

Gadolinium-enhancing lesions currently are considered the first detectable MR abnormalities in MS patients. However, the fact that vascular abnormalities detected using ultrahigh-field MRI can be seen even earlier “has important implications for treatment,” said Dr. Ge.

High-field-strength MRI might allow physicians to track the early disease activity and the effectiveness of treatments. This is particularly important now that disease-modifying therapies are available.

The immunomodulatory drugs—interferon β-1a IM (Avonex), interferon β-1b SC (Betaseron) glatiramer acetate SC (Copaxone), or interferon β-1a SC (Rebif) are approved for and are currently used in the United States as first-line therapies for MS to prevent relapses or disease progression.

Newer compounds approved by the Food and Drug Administration for use in MS include mitoxantrone (Novantrone) and natalizumab (Tysabri). Last year, natalizumab was reintroduced for the treatment of relapsing forms of MS with a black box warning about the risk of progressive multifocal leukoencephalopathy associated with treatment. The drug had previously been voluntarily suspended from the market following the development of PML in three patients treated with the drug (two for MS and one for Crohn's disease).

Ultra-high-field MRI shows an intimate relationship between lesions and centered small veins (arrows), suggesting a primarily vascular pathogenesis of MS lesions. Photos courtesy Dr. Yulin Ge

Clinical MRI studies are typically performed with 1.5-tesla (T) magnets, though the use of 3-T systems is becoming more common. The use of ultrahigh-field-strength MRI—using 7-T magnets—remains largely the domain of major research facilities such as New York University.

Dr. Yulin Ge, a radiologist at New York University, New York, and his colleagues have been using 7-T MRI to further their understanding of the pathophysiology of multiple sclerosis.

There are two main advantages to high-field MRI over imaging with conventional field-strength magnets. The higher signal intensity-to-noise ratio (SNR) that can be achieved with a stronger magnet strength allows for greater resolution, which in turn can improve the detection of lesions. Lesion counts may be 45% greater using a 4T system with better appreciation of tissue heterogeneity within lesions as compared with a 1.5-T system.

Separately, higher field strength also boosts susceptibility effects. Magnetic susceptibility is the degree of magnetization of a material in response to an applied magnetic field. Oxyhemoglobin in arterial blood has no substantial magnetic properties, but deoxyhemoglobin, which is present in the draining veins after the oxygen has been unloaded in the tissues, is strongly paramagnetic. It can thus serve as an intrinsic paramagnetic contrast agent, the effect of which is increased with greater field strength. This in turn improves the examination of microscopic venous structures, brain iron, and microbleeds. “So venous structures can be shown very well on high-field MRI,” Dr. Ge said in an interview.

The researchers have been able to directly see small vascular abnormalities—mainly small venous structures—at a very early stage of MS. “These findings have never been shown on conventional MR,” he said. High-field MRI detects these changes before the blood-brain barrier breakdown that can be seen on conventional MRI.

The MS lesions appear to be centered on a small venule. “We can see the abnormal signals on and around the venous wall,” Dr. Ge said. “And the lesion developed along the veins—along the venous course in the initial stage of development can be clearly seen on 7T MRI.” These findings may be direct in vivo evidence of the vascular pathogenesis of lesions, he added. While it takes only 6 minutes to perform such susceptibility-sensitive imaging, slices are 2 mm thick with pixel resolution of 0.2x0.2 mm

These vascular abnormalities are “not seen in one or two lesions but in many lesions,” he said (as shown in image A). The number of lesions with vascular abnormalities that can be detected “gives you a very important indication of disease activity beyond the resolution of conventional MRI.”

Gadolinium-enhancing lesions currently are considered the first detectable MR abnormalities in MS patients. However, the fact that vascular abnormalities detected using ultrahigh-field MRI can be seen even earlier “has important implications for treatment,” said Dr. Ge.

High-field-strength MRI might allow physicians to track the early disease activity and the effectiveness of treatments. This is particularly important now that disease-modifying therapies are available.

The immunomodulatory drugs—interferon β-1a IM (Avonex), interferon β-1b SC (Betaseron) glatiramer acetate SC (Copaxone), or interferon β-1a SC (Rebif) are approved for and are currently used in the United States as first-line therapies for MS to prevent relapses or disease progression.

Newer compounds approved by the Food and Drug Administration for use in MS include mitoxantrone (Novantrone) and natalizumab (Tysabri). Last year, natalizumab was reintroduced for the treatment of relapsing forms of MS with a black box warning about the risk of progressive multifocal leukoencephalopathy associated with treatment. The drug had previously been voluntarily suspended from the market following the development of PML in three patients treated with the drug (two for MS and one for Crohn's disease).

Ultra-high-field MRI shows an intimate relationship between lesions and centered small veins (arrows), suggesting a primarily vascular pathogenesis of MS lesions. Photos courtesy Dr. Yulin Ge

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

WASHINGTON — Whether to use a cardiac-focused CT protocol or a triple rule-out approach for assessing acute chest pain in the emergency department depends to some degree on what your clinical suspicions are, said Dr. Charles S. White at the annual meeting of the Society of Cardiovascular Computed Tomography.

“The question here is: Do you want to focus just on the coronaries, or do you want to expand the search and look for those 85% of other causes … that we might be able to detect with the triple rule out?” said Dr. White, chief of thoracic radiology at the University of Maryland Medical Center in Baltimore.

In the cardiac-focused CT approach, the field of view is limited to the area of the coronary arteries and therefore offers better spatial resolution of these vessels than the triple rule-out approach. This approach takes about 8 seconds on average and uses less radiation and contrast. The scanning direction is craniocaudal.

With the triple rule-out approach, the intent is to image the entire thorax, allowing visualization not only of the coronary arteries but the aorta and the pulmonary arteries. This approach allows evaluation for coronary artery disease, pulmonary embolism, and aortic dissection—earning it the triple rule-out moniker.

The trade-off for this expanded field of view is decreased spatial resolution, compared with the cardiac-focused approach. This approach involves a longer scan time (15 seconds) and involves greater radiation doses and more contrast than the cardiac-focused approach does. To minimize the chance of motion defects associated with a longer scan time, the scan is performed caudocranially. Motion is not as great a concern in the upper thorax, which is imaged last.

“The bottom line, I think, in terms of protocol between cardiac and triple rule out is that it depends on your level or suspicion that the cause of chest pain might be pulmonary embolism,” said Dr. White. “When you have some level of suspicion of a pulmonary embolism, a triple rule-out study may be appropriate. If you don't, then a dedicated CT [angiography] would be the way to go.”

In the University of Maryland Medical Center's ED, “We are generally still doing triple rule-out protocols,” said Dr. White. Cardiac-only studies can be ordered by emergency physicians as well. However, in their experience, most triple rule-out patients (75%) have calcium scores of zero or close to it. Roughly 15% have significant stenosis.

There are a number of challenges associated with using the triple rule-out protocol. Getting patient cooperation can be difficult. When using 64-slice CT, however, it's not crucial to get the heart rate down below 90 beats per minute. “As long as it's a stable heart rate, a 64-slice scanner will generally get you fairly good images,” said Dr. White.

Cost also is an issue with the triple rule-out approach, as is the greater radiation dose. The amount of technical labor required also is a concern. The ideal option is to have an in-house service to read the images on a 24-hour, 7-day a week basis.

However, industry is increasingly offering options to allow for off-hour coverage, such as the ability of radiologists and cardiologists to do preliminary reviews of images wherever they are.

“The bottom line is that about 50% of studies are negative. Off-hours, those patients are fairly easy to read … and you can probably send them home,” said Dr. White. The images of the remaining patients are evaluated further the next morning.

Dr. White disclosed that he has received research support from Phillips Medical Systems.

WASHINGTON — Whether to use a cardiac-focused CT protocol or a triple rule-out approach for assessing acute chest pain in the emergency department depends to some degree on what your clinical suspicions are, said Dr. Charles S. White at the annual meeting of the Society of Cardiovascular Computed Tomography.

“The question here is: Do you want to focus just on the coronaries, or do you want to expand the search and look for those 85% of other causes … that we might be able to detect with the triple rule out?” said Dr. White, chief of thoracic radiology at the University of Maryland Medical Center in Baltimore.

In the cardiac-focused CT approach, the field of view is limited to the area of the coronary arteries and therefore offers better spatial resolution of these vessels than the triple rule-out approach. This approach takes about 8 seconds on average and uses less radiation and contrast. The scanning direction is craniocaudal.

With the triple rule-out approach, the intent is to image the entire thorax, allowing visualization not only of the coronary arteries but the aorta and the pulmonary arteries. This approach allows evaluation for coronary artery disease, pulmonary embolism, and aortic dissection—earning it the triple rule-out moniker.

The trade-off for this expanded field of view is decreased spatial resolution, compared with the cardiac-focused approach. This approach involves a longer scan time (15 seconds) and involves greater radiation doses and more contrast than the cardiac-focused approach does. To minimize the chance of motion defects associated with a longer scan time, the scan is performed caudocranially. Motion is not as great a concern in the upper thorax, which is imaged last.

“The bottom line, I think, in terms of protocol between cardiac and triple rule out is that it depends on your level or suspicion that the cause of chest pain might be pulmonary embolism,” said Dr. White. “When you have some level of suspicion of a pulmonary embolism, a triple rule-out study may be appropriate. If you don't, then a dedicated CT [angiography] would be the way to go.”

In the University of Maryland Medical Center's ED, “We are generally still doing triple rule-out protocols,” said Dr. White. Cardiac-only studies can be ordered by emergency physicians as well. However, in their experience, most triple rule-out patients (75%) have calcium scores of zero or close to it. Roughly 15% have significant stenosis.

There are a number of challenges associated with using the triple rule-out protocol. Getting patient cooperation can be difficult. When using 64-slice CT, however, it's not crucial to get the heart rate down below 90 beats per minute. “As long as it's a stable heart rate, a 64-slice scanner will generally get you fairly good images,” said Dr. White.

Cost also is an issue with the triple rule-out approach, as is the greater radiation dose. The amount of technical labor required also is a concern. The ideal option is to have an in-house service to read the images on a 24-hour, 7-day a week basis.

However, industry is increasingly offering options to allow for off-hour coverage, such as the ability of radiologists and cardiologists to do preliminary reviews of images wherever they are.

“The bottom line is that about 50% of studies are negative. Off-hours, those patients are fairly easy to read … and you can probably send them home,” said Dr. White. The images of the remaining patients are evaluated further the next morning.

Dr. White disclosed that he has received research support from Phillips Medical Systems.

WASHINGTON — Whether to use a cardiac-focused CT protocol or a triple rule-out approach for assessing acute chest pain in the emergency department depends to some degree on what your clinical suspicions are, said Dr. Charles S. White at the annual meeting of the Society of Cardiovascular Computed Tomography.

“The question here is: Do you want to focus just on the coronaries, or do you want to expand the search and look for those 85% of other causes … that we might be able to detect with the triple rule out?” said Dr. White, chief of thoracic radiology at the University of Maryland Medical Center in Baltimore.

In the cardiac-focused CT approach, the field of view is limited to the area of the coronary arteries and therefore offers better spatial resolution of these vessels than the triple rule-out approach. This approach takes about 8 seconds on average and uses less radiation and contrast. The scanning direction is craniocaudal.

With the triple rule-out approach, the intent is to image the entire thorax, allowing visualization not only of the coronary arteries but the aorta and the pulmonary arteries. This approach allows evaluation for coronary artery disease, pulmonary embolism, and aortic dissection—earning it the triple rule-out moniker.

The trade-off for this expanded field of view is decreased spatial resolution, compared with the cardiac-focused approach. This approach involves a longer scan time (15 seconds) and involves greater radiation doses and more contrast than the cardiac-focused approach does. To minimize the chance of motion defects associated with a longer scan time, the scan is performed caudocranially. Motion is not as great a concern in the upper thorax, which is imaged last.

“The bottom line, I think, in terms of protocol between cardiac and triple rule out is that it depends on your level or suspicion that the cause of chest pain might be pulmonary embolism,” said Dr. White. “When you have some level of suspicion of a pulmonary embolism, a triple rule-out study may be appropriate. If you don't, then a dedicated CT [angiography] would be the way to go.”

In the University of Maryland Medical Center's ED, “We are generally still doing triple rule-out protocols,” said Dr. White. Cardiac-only studies can be ordered by emergency physicians as well. However, in their experience, most triple rule-out patients (75%) have calcium scores of zero or close to it. Roughly 15% have significant stenosis.

There are a number of challenges associated with using the triple rule-out protocol. Getting patient cooperation can be difficult. When using 64-slice CT, however, it's not crucial to get the heart rate down below 90 beats per minute. “As long as it's a stable heart rate, a 64-slice scanner will generally get you fairly good images,” said Dr. White.

Cost also is an issue with the triple rule-out approach, as is the greater radiation dose. The amount of technical labor required also is a concern. The ideal option is to have an in-house service to read the images on a 24-hour, 7-day a week basis.

However, industry is increasingly offering options to allow for off-hour coverage, such as the ability of radiologists and cardiologists to do preliminary reviews of images wherever they are.

“The bottom line is that about 50% of studies are negative. Off-hours, those patients are fairly easy to read … and you can probably send them home,” said Dr. White. The images of the remaining patients are evaluated further the next morning.

Dr. White disclosed that he has received research support from Phillips Medical Systems.

WASHINGTON — Coronary CT angiography appears to be a less expensive alternative to myocardial perfusion SPECT imaging as an initial diagnostic screen for coronary artery disease, according to an analysis of data from two large regional health plans presented at the annual meeting of the Society of Cardiovascular Computed Tomography.

The average 12-month downstream coronary artery disease-related cost for patients who underwent coronary CT angiography (CTA) as an initial screen for CAD was $1,716 lower per patient than for those who underwent SPECT, said Dr. James K. Min of Cornell University, New York. The average cost of a nuclear study ranged from $3,000 to $4,000.

“CT [angiography] may be a potential, cost-efficient alternative to SPECT for the initial evaluation of patients with suspected coronary artery disease,” said Dr. Min.

The researchers analyzed private payer data from two large regional health plans with more than 6.5 million members from 2002 to 2005. The database included membership information, pharmacy claims, and inpatient and outpatient service claims. The researchers identified patients who underwent CTA or MP SPECT imaging as an initial diagnostic screen for CAD. Information was collected for 1 year prior to and 1 year after the test.

Only patients without known CAD were included. These were patients who did not have any CAD-related procedure codes for the previous 12 months. CTA and MP SPECT claims included only those with coronary heart disease codes.

For each patient, the researchers calculated a cardiac risk score. The score was a weighted average of several risk factors, including use of digitalis, anticoagulants, antiplatelets, ACE inhibitors, β-blockers, antihypertensive medication, and antidiabetic medications, as well as other clinical cardiac conditions. The researchers also assessed each patient's overall health status using the Charleston Comorbidity Index.

Each patient in the CTA group was matched with four patients in the SPECT group based on age, sex, and cardiac risk score. Both groups had an average age of 51 years. About two-thirds of the patients in each group (68%) were women. The average cardiac risk score was 0.20 in the CTA group and 0.19 in the SPECT group.

A total of 1,833 patients were identified who had an initial diagnostic screen with CTA; they were matched with 7,332 patients who had SPECT imaging.

In addition to a cost difference for the two modalities, the researchers noted that the use of antiplatelet therapy was greater among SPECT patients after the initial diagnostic test. There was also a trend toward greater use of ACE inhibitors and statins in the SPECT group, though this did not achieve significance.

“In terms of follow-up diagnostic tests, patients who initially underwent CT angiography were more likely to undergo nuclear stress testing in the follow-up period, while patients who underwent nuclear stress testing were more likely to undergo invasive coronary angiography,” said Dr. Min. Looking at any diagnostic test, there was an 18% relative risk reduction in patients who underwent initial coronary evaluation with CT angiography.

The researchers also looked at clinical outcomes. Patients who underwent initial SPECT imaging had a higher rate of surgical or percutaneous interventions in the follow-up period compared with those who had CTA—1.2% compared with 0.4%, respectively. “CTA patients experienced lower rates of both hospitalization as well as angina or myocardial infarction,” said Dr. Min, who disclosed that he receives research support from GE Healthcare.

“From this we tentatively conclude that compared to MP SPECT patients, patients who underwent CT as an initial diagnostic test incurred lower 12-month total coronary disease-related costs,” he said.

CTA reveals severe, diffuse, mixed plaque in the left anterior descending artery.

Multidetector CT volume rendered image shows calcification in the LAD and RCA. Photos courtesy Dr. James K. Min

WASHINGTON — Coronary CT angiography appears to be a less expensive alternative to myocardial perfusion SPECT imaging as an initial diagnostic screen for coronary artery disease, according to an analysis of data from two large regional health plans presented at the annual meeting of the Society of Cardiovascular Computed Tomography.

The average 12-month downstream coronary artery disease-related cost for patients who underwent coronary CT angiography (CTA) as an initial screen for CAD was $1,716 lower per patient than for those who underwent SPECT, said Dr. James K. Min of Cornell University, New York. The average cost of a nuclear study ranged from $3,000 to $4,000.

“CT [angiography] may be a potential, cost-efficient alternative to SPECT for the initial evaluation of patients with suspected coronary artery disease,” said Dr. Min.

The researchers analyzed private payer data from two large regional health plans with more than 6.5 million members from 2002 to 2005. The database included membership information, pharmacy claims, and inpatient and outpatient service claims. The researchers identified patients who underwent CTA or MP SPECT imaging as an initial diagnostic screen for CAD. Information was collected for 1 year prior to and 1 year after the test.

Only patients without known CAD were included. These were patients who did not have any CAD-related procedure codes for the previous 12 months. CTA and MP SPECT claims included only those with coronary heart disease codes.

For each patient, the researchers calculated a cardiac risk score. The score was a weighted average of several risk factors, including use of digitalis, anticoagulants, antiplatelets, ACE inhibitors, β-blockers, antihypertensive medication, and antidiabetic medications, as well as other clinical cardiac conditions. The researchers also assessed each patient's overall health status using the Charleston Comorbidity Index.

Each patient in the CTA group was matched with four patients in the SPECT group based on age, sex, and cardiac risk score. Both groups had an average age of 51 years. About two-thirds of the patients in each group (68%) were women. The average cardiac risk score was 0.20 in the CTA group and 0.19 in the SPECT group.

A total of 1,833 patients were identified who had an initial diagnostic screen with CTA; they were matched with 7,332 patients who had SPECT imaging.

In addition to a cost difference for the two modalities, the researchers noted that the use of antiplatelet therapy was greater among SPECT patients after the initial diagnostic test. There was also a trend toward greater use of ACE inhibitors and statins in the SPECT group, though this did not achieve significance.

“In terms of follow-up diagnostic tests, patients who initially underwent CT angiography were more likely to undergo nuclear stress testing in the follow-up period, while patients who underwent nuclear stress testing were more likely to undergo invasive coronary angiography,” said Dr. Min. Looking at any diagnostic test, there was an 18% relative risk reduction in patients who underwent initial coronary evaluation with CT angiography.

The researchers also looked at clinical outcomes. Patients who underwent initial SPECT imaging had a higher rate of surgical or percutaneous interventions in the follow-up period compared with those who had CTA—1.2% compared with 0.4%, respectively. “CTA patients experienced lower rates of both hospitalization as well as angina or myocardial infarction,” said Dr. Min, who disclosed that he receives research support from GE Healthcare.

“From this we tentatively conclude that compared to MP SPECT patients, patients who underwent CT as an initial diagnostic test incurred lower 12-month total coronary disease-related costs,” he said.

CTA reveals severe, diffuse, mixed plaque in the left anterior descending artery.

Multidetector CT volume rendered image shows calcification in the LAD and RCA. Photos courtesy Dr. James K. Min

WASHINGTON — Coronary CT angiography appears to be a less expensive alternative to myocardial perfusion SPECT imaging as an initial diagnostic screen for coronary artery disease, according to an analysis of data from two large regional health plans presented at the annual meeting of the Society of Cardiovascular Computed Tomography.

The average 12-month downstream coronary artery disease-related cost for patients who underwent coronary CT angiography (CTA) as an initial screen for CAD was $1,716 lower per patient than for those who underwent SPECT, said Dr. James K. Min of Cornell University, New York. The average cost of a nuclear study ranged from $3,000 to $4,000.

“CT [angiography] may be a potential, cost-efficient alternative to SPECT for the initial evaluation of patients with suspected coronary artery disease,” said Dr. Min.

The researchers analyzed private payer data from two large regional health plans with more than 6.5 million members from 2002 to 2005. The database included membership information, pharmacy claims, and inpatient and outpatient service claims. The researchers identified patients who underwent CTA or MP SPECT imaging as an initial diagnostic screen for CAD. Information was collected for 1 year prior to and 1 year after the test.

Only patients without known CAD were included. These were patients who did not have any CAD-related procedure codes for the previous 12 months. CTA and MP SPECT claims included only those with coronary heart disease codes.

For each patient, the researchers calculated a cardiac risk score. The score was a weighted average of several risk factors, including use of digitalis, anticoagulants, antiplatelets, ACE inhibitors, β-blockers, antihypertensive medication, and antidiabetic medications, as well as other clinical cardiac conditions. The researchers also assessed each patient's overall health status using the Charleston Comorbidity Index.

Each patient in the CTA group was matched with four patients in the SPECT group based on age, sex, and cardiac risk score. Both groups had an average age of 51 years. About two-thirds of the patients in each group (68%) were women. The average cardiac risk score was 0.20 in the CTA group and 0.19 in the SPECT group.

A total of 1,833 patients were identified who had an initial diagnostic screen with CTA; they were matched with 7,332 patients who had SPECT imaging.

In addition to a cost difference for the two modalities, the researchers noted that the use of antiplatelet therapy was greater among SPECT patients after the initial diagnostic test. There was also a trend toward greater use of ACE inhibitors and statins in the SPECT group, though this did not achieve significance.

“In terms of follow-up diagnostic tests, patients who initially underwent CT angiography were more likely to undergo nuclear stress testing in the follow-up period, while patients who underwent nuclear stress testing were more likely to undergo invasive coronary angiography,” said Dr. Min. Looking at any diagnostic test, there was an 18% relative risk reduction in patients who underwent initial coronary evaluation with CT angiography.

The researchers also looked at clinical outcomes. Patients who underwent initial SPECT imaging had a higher rate of surgical or percutaneous interventions in the follow-up period compared with those who had CTA—1.2% compared with 0.4%, respectively. “CTA patients experienced lower rates of both hospitalization as well as angina or myocardial infarction,” said Dr. Min, who disclosed that he receives research support from GE Healthcare.

“From this we tentatively conclude that compared to MP SPECT patients, patients who underwent CT as an initial diagnostic test incurred lower 12-month total coronary disease-related costs,” he said.

CTA reveals severe, diffuse, mixed plaque in the left anterior descending artery.

Multidetector CT volume rendered image shows calcification in the LAD and RCA. Photos courtesy Dr. James K. Min

CHICAGO – Adding flaxseed to the diets of men with prostate cancer appears to slow tumor growth, according to data presented at the annual meeting of the American Society of Clinical Oncology.

In a study of 161 men with prostate cancer, those who consumed 30 g of ground flaxseed daily had significantly lower levels of the tumor proliferation markerMIB-1 than did men on their usual diet.

“Prostate cancer proliferation rates were significantly lower in men assigned to flaxseed supplementation,” said Wendy Demark-Wahnefried, Ph.D., a researcher in the school of nursing at Duke University, Durham, N.C.

Flaxseed is a rich source of lignans, which have been shown to affect androgen metabolism and have antimitotic, antiangiogenic, antioxidant, and estrogenic effects. Flaxseed also is a rich source of omega-3 fatty acids, which play a role in cell membrane function, inhibit protein kinase activity, and increase natural killer-cell activity. Previous studies have suggested, too, that a low-fat diet might help prevent prostate cancer.

The study included men with pathologically confirmed prostate cancer who were electing prostatectomy as their primary treatment. Their mean age was 59 years, and 70% were white. They had to be at least 21 days from scheduled surgery and not on neoadjuvant therapy. The men could not have started any new supplements (excluding multivitamins) during or within 3 months of the study period. Also, they could not use antibiotics during or 7 days prior to the study, because normal gut flora is necessary to process lignans.

The men were randomized to supplementation with flaxseed (40 patients), a low-fat diet (40), flaxseed plus a low-fat diet (40), or their usual diet (41). Men on their usual diet served as controls. Men receiving flaxseed supplementation (donated by Enreco Inc.) consumed 30 g of ground flaxseed daily. Men on a low-fat diet were limited to receiving less than 20% of daily calories from fat.

At baseline and immediately prior to surgery, blood, urine, and seminal fluid were collected, and the men completed questionnaires. Following surgery, prostatic tissue was analyzed. Men were stratified by race and combined Gleason score (classified as either above or below 7) so that the groups had similar representation of aggressive disease. Overall, 68% of men had a Gleason score of less than 7.

Men in all four groups followed their protocols for roughly 30 days. Adherence (confirmed by biomarkers) was high in the three intervention groups: almost 7 days per week. The attrition rate of 9% was due mainly to men deciding against surgery, or advancement of their surgery date.

Men in the flaxseed-only group and those in the combination flaxseed/low-fat diet group had significantly lower levels of MIB-1, indicating lower rates of tumor proliferation, expressed as the ratio of cancer cells that are actively dividing to those that are not dividing: 1.66 in the flaxseed group and 1.5 in the combination group, compared with 2.56 in the low-fat diet group and 3.23 in the control group. Other biomarkers that are associated with prostate cancer, including apoptosis and androgen metabolism, did differ significantly.

“Unfortunately, we did not see what we'd been able to find in our pilot studies, which was a reduction in testosterone levels and PSA [prostate-specific antigen] in our flaxseed groups,” Dr. Demark-Wahnefried said. “In our control group, the PSA and androgen levels really bottomed out. So there were no differences detected.”

The researchers had speculated that flaxseed might reduce cancer proliferation by altering androgen metabolism, she said. They hope to identify the mechanism in future studies.

There were no differences between the groups in terms of side effects.

Flaxseed might reduce cancer proliferation by altering androgen metabolism. DR. DEMARK-WAHNEFRIED

CHICAGO – Adding flaxseed to the diets of men with prostate cancer appears to slow tumor growth, according to data presented at the annual meeting of the American Society of Clinical Oncology.

In a study of 161 men with prostate cancer, those who consumed 30 g of ground flaxseed daily had significantly lower levels of the tumor proliferation markerMIB-1 than did men on their usual diet.

“Prostate cancer proliferation rates were significantly lower in men assigned to flaxseed supplementation,” said Wendy Demark-Wahnefried, Ph.D., a researcher in the school of nursing at Duke University, Durham, N.C.

Flaxseed is a rich source of lignans, which have been shown to affect androgen metabolism and have antimitotic, antiangiogenic, antioxidant, and estrogenic effects. Flaxseed also is a rich source of omega-3 fatty acids, which play a role in cell membrane function, inhibit protein kinase activity, and increase natural killer-cell activity. Previous studies have suggested, too, that a low-fat diet might help prevent prostate cancer.

The study included men with pathologically confirmed prostate cancer who were electing prostatectomy as their primary treatment. Their mean age was 59 years, and 70% were white. They had to be at least 21 days from scheduled surgery and not on neoadjuvant therapy. The men could not have started any new supplements (excluding multivitamins) during or within 3 months of the study period. Also, they could not use antibiotics during or 7 days prior to the study, because normal gut flora is necessary to process lignans.

The men were randomized to supplementation with flaxseed (40 patients), a low-fat diet (40), flaxseed plus a low-fat diet (40), or their usual diet (41). Men on their usual diet served as controls. Men receiving flaxseed supplementation (donated by Enreco Inc.) consumed 30 g of ground flaxseed daily. Men on a low-fat diet were limited to receiving less than 20% of daily calories from fat.

At baseline and immediately prior to surgery, blood, urine, and seminal fluid were collected, and the men completed questionnaires. Following surgery, prostatic tissue was analyzed. Men were stratified by race and combined Gleason score (classified as either above or below 7) so that the groups had similar representation of aggressive disease. Overall, 68% of men had a Gleason score of less than 7.

Men in all four groups followed their protocols for roughly 30 days. Adherence (confirmed by biomarkers) was high in the three intervention groups: almost 7 days per week. The attrition rate of 9% was due mainly to men deciding against surgery, or advancement of their surgery date.

Men in the flaxseed-only group and those in the combination flaxseed/low-fat diet group had significantly lower levels of MIB-1, indicating lower rates of tumor proliferation, expressed as the ratio of cancer cells that are actively dividing to those that are not dividing: 1.66 in the flaxseed group and 1.5 in the combination group, compared with 2.56 in the low-fat diet group and 3.23 in the control group. Other biomarkers that are associated with prostate cancer, including apoptosis and androgen metabolism, did differ significantly.

“Unfortunately, we did not see what we'd been able to find in our pilot studies, which was a reduction in testosterone levels and PSA [prostate-specific antigen] in our flaxseed groups,” Dr. Demark-Wahnefried said. “In our control group, the PSA and androgen levels really bottomed out. So there were no differences detected.”

The researchers had speculated that flaxseed might reduce cancer proliferation by altering androgen metabolism, she said. They hope to identify the mechanism in future studies.

There were no differences between the groups in terms of side effects.

Flaxseed might reduce cancer proliferation by altering androgen metabolism. DR. DEMARK-WAHNEFRIED

CHICAGO – Adding flaxseed to the diets of men with prostate cancer appears to slow tumor growth, according to data presented at the annual meeting of the American Society of Clinical Oncology.

In a study of 161 men with prostate cancer, those who consumed 30 g of ground flaxseed daily had significantly lower levels of the tumor proliferation markerMIB-1 than did men on their usual diet.

“Prostate cancer proliferation rates were significantly lower in men assigned to flaxseed supplementation,” said Wendy Demark-Wahnefried, Ph.D., a researcher in the school of nursing at Duke University, Durham, N.C.

Flaxseed is a rich source of lignans, which have been shown to affect androgen metabolism and have antimitotic, antiangiogenic, antioxidant, and estrogenic effects. Flaxseed also is a rich source of omega-3 fatty acids, which play a role in cell membrane function, inhibit protein kinase activity, and increase natural killer-cell activity. Previous studies have suggested, too, that a low-fat diet might help prevent prostate cancer.

The study included men with pathologically confirmed prostate cancer who were electing prostatectomy as their primary treatment. Their mean age was 59 years, and 70% were white. They had to be at least 21 days from scheduled surgery and not on neoadjuvant therapy. The men could not have started any new supplements (excluding multivitamins) during or within 3 months of the study period. Also, they could not use antibiotics during or 7 days prior to the study, because normal gut flora is necessary to process lignans.

The men were randomized to supplementation with flaxseed (40 patients), a low-fat diet (40), flaxseed plus a low-fat diet (40), or their usual diet (41). Men on their usual diet served as controls. Men receiving flaxseed supplementation (donated by Enreco Inc.) consumed 30 g of ground flaxseed daily. Men on a low-fat diet were limited to receiving less than 20% of daily calories from fat.

At baseline and immediately prior to surgery, blood, urine, and seminal fluid were collected, and the men completed questionnaires. Following surgery, prostatic tissue was analyzed. Men were stratified by race and combined Gleason score (classified as either above or below 7) so that the groups had similar representation of aggressive disease. Overall, 68% of men had a Gleason score of less than 7.

Men in all four groups followed their protocols for roughly 30 days. Adherence (confirmed by biomarkers) was high in the three intervention groups: almost 7 days per week. The attrition rate of 9% was due mainly to men deciding against surgery, or advancement of their surgery date.

Men in the flaxseed-only group and those in the combination flaxseed/low-fat diet group had significantly lower levels of MIB-1, indicating lower rates of tumor proliferation, expressed as the ratio of cancer cells that are actively dividing to those that are not dividing: 1.66 in the flaxseed group and 1.5 in the combination group, compared with 2.56 in the low-fat diet group and 3.23 in the control group. Other biomarkers that are associated with prostate cancer, including apoptosis and androgen metabolism, did differ significantly.

“Unfortunately, we did not see what we'd been able to find in our pilot studies, which was a reduction in testosterone levels and PSA [prostate-specific antigen] in our flaxseed groups,” Dr. Demark-Wahnefried said. “In our control group, the PSA and androgen levels really bottomed out. So there were no differences detected.”

The researchers had speculated that flaxseed might reduce cancer proliferation by altering androgen metabolism, she said. They hope to identify the mechanism in future studies.

There were no differences between the groups in terms of side effects.

Flaxseed might reduce cancer proliferation by altering androgen metabolism. DR. DEMARK-WAHNEFRIED

CHICAGO — American ginseng showed promise for reducing fatigue among patients with several types of cancer in a placebo-controlled, randomized pilot trial presented at the annual meeting of the American Society of Clinical Oncology.

Patients on higher doses of ginseng—1,000 mg and 2,000 mg/day—had a better mean change on the vitality subscale of the SF-36 than did those on placebo or on the 750-mg/day dose during 8 weeks of treatment.

“We believe that ginseng doses of 1,000–2,000 mg should be evaluated [further] for the treatment of cancer-related fatigue,” said Debra Barton, Ph.D., an associate professor of oncology at the Mayo Clinic in Rochester, Minn.

Up to 90% of cancer survivors experience fatigue. So far, exercise is the only treatment with a well-established evidence base.

Evidence from animal studies has suggested that American ginseng could be useful for treating fatigue in these patients, but there have been no well-designed clinical trials.

Results from a randomized, controlled trial are welcome news for many physicians who struggle with what to tell their patients about herbal supplements, said Dr. Bruce D. Cheson, director of hematology services at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital in Washington, and moderator of a press briefing on alternative therapies.

“One of the most common questions my patients ask me is about these things they have snookered away in their purses and pocketbooks. They pull out a whole big bag of [supplements] and say, 'Can I take this?' or 'Is this going to help me?' … Most of the time we can't answer that,” Dr. Cheson said.

For this study, 282 patients were randomized to placebo or to 750 mg, 1,000 mg, or 2,000 mg/day of American ginseng for 8 weeks. Patients assigned to the intervention received powdered extract of 4-year-old Wisconsin ginseng root in capsules. The placebo group received matching placebo capsules. The ginseng capsules were standardized to a 5% ginsenoside content. Ginsenosides, found exclusively in ginseng, are phytoestrogens with a common steroidlike chemical structure; they are thought to be the active compounds responsible for reducing fatigue.

Patients were included if they had cancer-related fatigue rated as at least 4 on a 0- to 10-point scale. They also had to have fatigue for at least a month but no other reasons for fatigue. They could not be on any treatments for fatigue.

Patients were assessed using the vitality subscale of the SF-36 health survey (0–100 points), a linear analog self-assessment scale, and the Global Impression of Change tool.

A total of 175 patients completed the trial. Those who dropped out were fairly evenly distributed among the groups. Patient were more likely to drop out during the first 4 weeks. Patients who dropped out were also twice as likely to have stage III or IV disease. Patients on 1,000-mg and 2,000-mg doses had mean improvements of 14.6 and 10.5, respectively, on the vitality subscale of the SF-36. Those on placebo or 750 mg had improvements of 7.3 and 7.8, respectively.

Patients on 1,000 mg had the greatest mean change in overall physical well-being, improving 12 points on the 100-point scale.

Those on placebo, 750 mg, and 2,000 mg improved by 5.6, 5.3, and 6.5 points, respectively. Only 10% of patients in the placebo and 750-mg groups perceived that their fatigue improved moderately or very much, compared with 25% of those in the 1,000-mg group and 27% of those in the 2,000-mg group.

“[Roughly] three times as many patients in the higher-dose arms were more likely to be satisfied with treatment” than those on placebo, Dr. Barton said. A third of patients in the 1,000-mg and 2,000-mg groups were satisfied, compared with 13% in the placebo group and 24% in the 750-mg group.

Side effects were assessed using a questionnaire that asked patients to rate various symptoms, such as nausea, on a scale of 0–10. There was no suggestion of gastrointestinal symptoms, neurologic symptoms, or sleep trouble.

Despite the positive findings, patients shouldn't rush right out and start taking ginseng, Dr. Barton indicated.

“As a physician or nurse, what I would recommend patients do is the evidence-based, proven treatment for fatigue, which right now is exercise,” she said. “If a patient really insisted that they wanted to take something now and they wanted to take ginseng, it's their right to do so. I would guide them to a product that I knew had ginseng in it.”

Supplement purity is often a stumbling block in trial design and something that patients often don't consider.

When patients buy supplements, “they may not be getting pure anything,” Dr. Cheson pointed out.

The National Center for Complementary and Alternative Medicine offers tips to help physicians and patients evaluate dietary supplements at http://nccam.nih.gov/health/supplements.htm

Despite the positive findings, patients shouldn't rush right out and start taking ginseng. DR. BARTON

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — American ginseng showed promise for reducing fatigue among patients with several types of cancer in a placebo-controlled, randomized pilot trial presented at the annual meeting of the American Society of Clinical Oncology.

Patients on higher doses of ginseng—1,000 mg and 2,000 mg/day—had a better mean change on the vitality subscale of the SF-36 than did those on placebo or on the 750-mg/day dose during 8 weeks of treatment.

“We believe that ginseng doses of 1,000–2,000 mg should be evaluated [further] for the treatment of cancer-related fatigue,” said Debra Barton, Ph.D., an associate professor of oncology at the Mayo Clinic in Rochester, Minn.

Up to 90% of cancer survivors experience fatigue. So far, exercise is the only treatment with a well-established evidence base.

Evidence from animal studies has suggested that American ginseng could be useful for treating fatigue in these patients, but there have been no well-designed clinical trials.

Results from a randomized, controlled trial are welcome news for many physicians who struggle with what to tell their patients about herbal supplements, said Dr. Bruce D. Cheson, director of hematology services at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital in Washington, and moderator of a press briefing on alternative therapies.

“One of the most common questions my patients ask me is about these things they have snookered away in their purses and pocketbooks. They pull out a whole big bag of [supplements] and say, 'Can I take this?' or 'Is this going to help me?' … Most of the time we can't answer that,” Dr. Cheson said.

For this study, 282 patients were randomized to placebo or to 750 mg, 1,000 mg, or 2,000 mg/day of American ginseng for 8 weeks. Patients assigned to the intervention received powdered extract of 4-year-old Wisconsin ginseng root in capsules. The placebo group received matching placebo capsules. The ginseng capsules were standardized to a 5% ginsenoside content. Ginsenosides, found exclusively in ginseng, are phytoestrogens with a common steroidlike chemical structure; they are thought to be the active compounds responsible for reducing fatigue.

Patients were included if they had cancer-related fatigue rated as at least 4 on a 0- to 10-point scale. They also had to have fatigue for at least a month but no other reasons for fatigue. They could not be on any treatments for fatigue.

Patients were assessed using the vitality subscale of the SF-36 health survey (0–100 points), a linear analog self-assessment scale, and the Global Impression of Change tool.

A total of 175 patients completed the trial. Those who dropped out were fairly evenly distributed among the groups. Patient were more likely to drop out during the first 4 weeks. Patients who dropped out were also twice as likely to have stage III or IV disease. Patients on 1,000-mg and 2,000-mg doses had mean improvements of 14.6 and 10.5, respectively, on the vitality subscale of the SF-36. Those on placebo or 750 mg had improvements of 7.3 and 7.8, respectively.

Patients on 1,000 mg had the greatest mean change in overall physical well-being, improving 12 points on the 100-point scale.

Those on placebo, 750 mg, and 2,000 mg improved by 5.6, 5.3, and 6.5 points, respectively. Only 10% of patients in the placebo and 750-mg groups perceived that their fatigue improved moderately or very much, compared with 25% of those in the 1,000-mg group and 27% of those in the 2,000-mg group.

“[Roughly] three times as many patients in the higher-dose arms were more likely to be satisfied with treatment” than those on placebo, Dr. Barton said. A third of patients in the 1,000-mg and 2,000-mg groups were satisfied, compared with 13% in the placebo group and 24% in the 750-mg group.

Side effects were assessed using a questionnaire that asked patients to rate various symptoms, such as nausea, on a scale of 0–10. There was no suggestion of gastrointestinal symptoms, neurologic symptoms, or sleep trouble.

Despite the positive findings, patients shouldn't rush right out and start taking ginseng, Dr. Barton indicated.

“As a physician or nurse, what I would recommend patients do is the evidence-based, proven treatment for fatigue, which right now is exercise,” she said. “If a patient really insisted that they wanted to take something now and they wanted to take ginseng, it's their right to do so. I would guide them to a product that I knew had ginseng in it.”

Supplement purity is often a stumbling block in trial design and something that patients often don't consider.

When patients buy supplements, “they may not be getting pure anything,” Dr. Cheson pointed out.

The National Center for Complementary and Alternative Medicine offers tips to help physicians and patients evaluate dietary supplements at http://nccam.nih.gov/health/supplements.htm

Despite the positive findings, patients shouldn't rush right out and start taking ginseng. DR. BARTON

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — American ginseng showed promise for reducing fatigue among patients with several types of cancer in a placebo-controlled, randomized pilot trial presented at the annual meeting of the American Society of Clinical Oncology.

Patients on higher doses of ginseng—1,000 mg and 2,000 mg/day—had a better mean change on the vitality subscale of the SF-36 than did those on placebo or on the 750-mg/day dose during 8 weeks of treatment.

“We believe that ginseng doses of 1,000–2,000 mg should be evaluated [further] for the treatment of cancer-related fatigue,” said Debra Barton, Ph.D., an associate professor of oncology at the Mayo Clinic in Rochester, Minn.

Up to 90% of cancer survivors experience fatigue. So far, exercise is the only treatment with a well-established evidence base.

Evidence from animal studies has suggested that American ginseng could be useful for treating fatigue in these patients, but there have been no well-designed clinical trials.

Results from a randomized, controlled trial are welcome news for many physicians who struggle with what to tell their patients about herbal supplements, said Dr. Bruce D. Cheson, director of hematology services at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital in Washington, and moderator of a press briefing on alternative therapies.

“One of the most common questions my patients ask me is about these things they have snookered away in their purses and pocketbooks. They pull out a whole big bag of [supplements] and say, 'Can I take this?' or 'Is this going to help me?' … Most of the time we can't answer that,” Dr. Cheson said.

For this study, 282 patients were randomized to placebo or to 750 mg, 1,000 mg, or 2,000 mg/day of American ginseng for 8 weeks. Patients assigned to the intervention received powdered extract of 4-year-old Wisconsin ginseng root in capsules. The placebo group received matching placebo capsules. The ginseng capsules were standardized to a 5% ginsenoside content. Ginsenosides, found exclusively in ginseng, are phytoestrogens with a common steroidlike chemical structure; they are thought to be the active compounds responsible for reducing fatigue.

Patients were included if they had cancer-related fatigue rated as at least 4 on a 0- to 10-point scale. They also had to have fatigue for at least a month but no other reasons for fatigue. They could not be on any treatments for fatigue.

Patients were assessed using the vitality subscale of the SF-36 health survey (0–100 points), a linear analog self-assessment scale, and the Global Impression of Change tool.

A total of 175 patients completed the trial. Those who dropped out were fairly evenly distributed among the groups. Patient were more likely to drop out during the first 4 weeks. Patients who dropped out were also twice as likely to have stage III or IV disease. Patients on 1,000-mg and 2,000-mg doses had mean improvements of 14.6 and 10.5, respectively, on the vitality subscale of the SF-36. Those on placebo or 750 mg had improvements of 7.3 and 7.8, respectively.

Patients on 1,000 mg had the greatest mean change in overall physical well-being, improving 12 points on the 100-point scale.

Those on placebo, 750 mg, and 2,000 mg improved by 5.6, 5.3, and 6.5 points, respectively. Only 10% of patients in the placebo and 750-mg groups perceived that their fatigue improved moderately or very much, compared with 25% of those in the 1,000-mg group and 27% of those in the 2,000-mg group.

“[Roughly] three times as many patients in the higher-dose arms were more likely to be satisfied with treatment” than those on placebo, Dr. Barton said. A third of patients in the 1,000-mg and 2,000-mg groups were satisfied, compared with 13% in the placebo group and 24% in the 750-mg group.

Side effects were assessed using a questionnaire that asked patients to rate various symptoms, such as nausea, on a scale of 0–10. There was no suggestion of gastrointestinal symptoms, neurologic symptoms, or sleep trouble.

Despite the positive findings, patients shouldn't rush right out and start taking ginseng, Dr. Barton indicated.

“As a physician or nurse, what I would recommend patients do is the evidence-based, proven treatment for fatigue, which right now is exercise,” she said. “If a patient really insisted that they wanted to take something now and they wanted to take ginseng, it's their right to do so. I would guide them to a product that I knew had ginseng in it.”

Supplement purity is often a stumbling block in trial design and something that patients often don't consider.

When patients buy supplements, “they may not be getting pure anything,” Dr. Cheson pointed out.

The National Center for Complementary and Alternative Medicine offers tips to help physicians and patients evaluate dietary supplements at http://nccam.nih.gov/health/supplements.htm

Despite the positive findings, patients shouldn't rush right out and start taking ginseng. DR. BARTON

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Tetracycline may reduce the severity of rashes associated with epidermal growth factor receptor inhibitors, such as gefitinib and cetuximab, but the antibiotic doesn't seem to prevent such rashes.

More than 75% of patients on epidermal growth factor receptor (EGFR) inhibitors develop an acneiform rash. The rash can be very problematic for patients, said Dr. Aminah Jatoi, a professor of oncology at the Mayo Clinic in Rochester, Minn.

Dr. Jatoi and her colleagues randomized 61 cancer patients to 500 mg oral tetracycline twice daily or placebo twice daily for 1 month. Patients were included if they had started an EGFR inhibitor within 7 days of enrollment and did not have a rash.

“Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic deserves further study,” Dr. Jatoi said at the annual meeting of the American Society of Clinical Oncology.

Rashes were assessed by physicians and patients over an 8-week period. Physicians submitted monthly reports using the Common Terminology Criteria for Adverse Events v3.0. Patients submitted weekly reports, including the answers to a brief questionnaire on rash incidence (the Skindex-16), and an EGFR inhibitor compliance questionnaire.

A small portion of patients—10% in the treatment arm and 17% in the placebo arm—were being treated with gefitinib. An additional 35% and 40% were being treated with cetuximab in the treatment and placebo arms, respectively. The remaining 55% and 43% were taking other EGFR inhibitors (EGFR tyrosine kinase inhibitors) in the treatment and placebo arms, respectively.

“With regard to the primary end point [rash prevention], this was a negative study,” Dr. Jatoi said. Physician-reported rash incidence was comparable between the two arms at weeks 4 and 8. At week 4, the incidence was 70% and 76% for the treatment and placebo arms, respectively. Likewise at week 8, the incidence was 87% and 84% for the treatment and placebo arms, respectively. Patient-reported results were similar.

In terms of physician-reported rash severity, significantly fewer patients (17%) on tetracycline had rashes with grade 2 or greater at 4 weeks, compared with those on placebo (55%). However, the difference was not significant at 8 weeks—27% in the tetracycline group vs. 47% in the placebo group. Patient-reported results were similar.

Patients on tetracycline did report less itching on the Skindex-16 starting at week 2, however.

Three patients in each arm stopped taking EGFR inhibitors early because of cancer-related issues. Adverse events were comparable in both treatment arms.

“We invite caution, however, in interpreting these results for two reasons. First, this was a secondary end point not a primary end point. Secondly, the numbers are very small. Dropout rates were quite high over time,” Dr. Jatoi said.

The issue of EGFR inhibitor-induced rash is particularly troublesome for patients, because it has been suggested that the presence of skin rash may be associated with tumor response.

“Patients are sometimes finding themselves in quandary. They're getting a severe rash and it bothers them. Yet at the same time they're saying, 'My tumor may well be responding to this drug. I can't stop taking this drug and yet I want to,'” Dr. Jatoi said.

CHICAGO — Tetracycline may reduce the severity of rashes associated with epidermal growth factor receptor inhibitors, such as gefitinib and cetuximab, but the antibiotic doesn't seem to prevent such rashes.

More than 75% of patients on epidermal growth factor receptor (EGFR) inhibitors develop an acneiform rash. The rash can be very problematic for patients, said Dr. Aminah Jatoi, a professor of oncology at the Mayo Clinic in Rochester, Minn.

Dr. Jatoi and her colleagues randomized 61 cancer patients to 500 mg oral tetracycline twice daily or placebo twice daily for 1 month. Patients were included if they had started an EGFR inhibitor within 7 days of enrollment and did not have a rash.

“Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic deserves further study,” Dr. Jatoi said at the annual meeting of the American Society of Clinical Oncology.

Rashes were assessed by physicians and patients over an 8-week period. Physicians submitted monthly reports using the Common Terminology Criteria for Adverse Events v3.0. Patients submitted weekly reports, including the answers to a brief questionnaire on rash incidence (the Skindex-16), and an EGFR inhibitor compliance questionnaire.

A small portion of patients—10% in the treatment arm and 17% in the placebo arm—were being treated with gefitinib. An additional 35% and 40% were being treated with cetuximab in the treatment and placebo arms, respectively. The remaining 55% and 43% were taking other EGFR inhibitors (EGFR tyrosine kinase inhibitors) in the treatment and placebo arms, respectively.

“With regard to the primary end point [rash prevention], this was a negative study,” Dr. Jatoi said. Physician-reported rash incidence was comparable between the two arms at weeks 4 and 8. At week 4, the incidence was 70% and 76% for the treatment and placebo arms, respectively. Likewise at week 8, the incidence was 87% and 84% for the treatment and placebo arms, respectively. Patient-reported results were similar.

In terms of physician-reported rash severity, significantly fewer patients (17%) on tetracycline had rashes with grade 2 or greater at 4 weeks, compared with those on placebo (55%). However, the difference was not significant at 8 weeks—27% in the tetracycline group vs. 47% in the placebo group. Patient-reported results were similar.

Patients on tetracycline did report less itching on the Skindex-16 starting at week 2, however.

Three patients in each arm stopped taking EGFR inhibitors early because of cancer-related issues. Adverse events were comparable in both treatment arms.

“We invite caution, however, in interpreting these results for two reasons. First, this was a secondary end point not a primary end point. Secondly, the numbers are very small. Dropout rates were quite high over time,” Dr. Jatoi said.

The issue of EGFR inhibitor-induced rash is particularly troublesome for patients, because it has been suggested that the presence of skin rash may be associated with tumor response.

“Patients are sometimes finding themselves in quandary. They're getting a severe rash and it bothers them. Yet at the same time they're saying, 'My tumor may well be responding to this drug. I can't stop taking this drug and yet I want to,'” Dr. Jatoi said.

CHICAGO — Tetracycline may reduce the severity of rashes associated with epidermal growth factor receptor inhibitors, such as gefitinib and cetuximab, but the antibiotic doesn't seem to prevent such rashes.

More than 75% of patients on epidermal growth factor receptor (EGFR) inhibitors develop an acneiform rash. The rash can be very problematic for patients, said Dr. Aminah Jatoi, a professor of oncology at the Mayo Clinic in Rochester, Minn.

Dr. Jatoi and her colleagues randomized 61 cancer patients to 500 mg oral tetracycline twice daily or placebo twice daily for 1 month. Patients were included if they had started an EGFR inhibitor within 7 days of enrollment and did not have a rash.

“Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic deserves further study,” Dr. Jatoi said at the annual meeting of the American Society of Clinical Oncology.

Rashes were assessed by physicians and patients over an 8-week period. Physicians submitted monthly reports using the Common Terminology Criteria for Adverse Events v3.0. Patients submitted weekly reports, including the answers to a brief questionnaire on rash incidence (the Skindex-16), and an EGFR inhibitor compliance questionnaire.

A small portion of patients—10% in the treatment arm and 17% in the placebo arm—were being treated with gefitinib. An additional 35% and 40% were being treated with cetuximab in the treatment and placebo arms, respectively. The remaining 55% and 43% were taking other EGFR inhibitors (EGFR tyrosine kinase inhibitors) in the treatment and placebo arms, respectively.

“With regard to the primary end point [rash prevention], this was a negative study,” Dr. Jatoi said. Physician-reported rash incidence was comparable between the two arms at weeks 4 and 8. At week 4, the incidence was 70% and 76% for the treatment and placebo arms, respectively. Likewise at week 8, the incidence was 87% and 84% for the treatment and placebo arms, respectively. Patient-reported results were similar.

In terms of physician-reported rash severity, significantly fewer patients (17%) on tetracycline had rashes with grade 2 or greater at 4 weeks, compared with those on placebo (55%). However, the difference was not significant at 8 weeks—27% in the tetracycline group vs. 47% in the placebo group. Patient-reported results were similar.

Patients on tetracycline did report less itching on the Skindex-16 starting at week 2, however.

Three patients in each arm stopped taking EGFR inhibitors early because of cancer-related issues. Adverse events were comparable in both treatment arms.

“We invite caution, however, in interpreting these results for two reasons. First, this was a secondary end point not a primary end point. Secondly, the numbers are very small. Dropout rates were quite high over time,” Dr. Jatoi said.

The issue of EGFR inhibitor-induced rash is particularly troublesome for patients, because it has been suggested that the presence of skin rash may be associated with tumor response.

“Patients are sometimes finding themselves in quandary. They're getting a severe rash and it bothers them. Yet at the same time they're saying, 'My tumor may well be responding to this drug. I can't stop taking this drug and yet I want to,'” Dr. Jatoi said.

WASHINGTON — Rosiglitazone shows some promise in reducing ulcerative colitis activity and may offer an alternative to conventional therapy for patients who fail to respond to the latter approach or can't tolerate it, said Dr. James D. Lewis at the annual Digestive Disease Week.

Rosiglitazone (Avandia) reduced disease activity significantly, compared with placebo in patients with mild to moderate ulcerative colitis activity.

In the study of 105 patients, 44% of those taking rosiglitazone achieved clinical remission—defined as at least a 2-point drop in the disease activity index at 12 weeks—compared with 23% of those on placebo.

Fifty-two patients were randomized to receive 4 mg rosiglitazone twice daily, and 53 received placebo. Most of the patients were male (79%), with an average age of 44 years.

“Rosiglitazone may represent a novel approach to the treatment of mild to moderately active ulcerative colitis and conceivably has a role in those patients who fail to respond to or are unable to tolerate 5-aminosalicylic acid therapy,” said Dr. Lewis, associate director of the University of Pennsylvania Health System's Inflammatory Bowel Disease Program in Philadelphia.

Dr. Lewis disclosed that he has received grants and research support from GlaxoSmithKline, maker of Avandia. The company also supplied rosiglitazone for this study.

Patients had to have been treated with at least 2 g/day of 5-aminosalicylic acid for at least 4 weeks prior to randomization, or they had to have documented intolerance to this therapy. Corticosteroids were allowed, as long as the patient was on a stable dose for at least 4 weeks or taking no more than 20 mg/day of prednisone or the equivalent.

Immunomodulators (azathioprine and 6-mercaptopurine) were also allowed if the patient had been treated with these for at least 4 months and was on a stable dose for at least 2 months. Rectal therapies were also allowed, as long as the dose had been stable for at least 2 weeks prior to randomization.

Patients were excluded if they had diabetes mellitus requiring treatment with a hypoglycemic agent or had New York Heart Association class III or IV heart failure. Patients were also excluded if they were taking cyclosporine, anti-tumor necrosis factor-α drugs, or methotrexate within 2 months of the study.

The researchers used a modified version of the Sutherland and Mayo disease activity indices to assess disease activity. This index (DAI) included four components: stool frequency, physician global assessment, rectal bleeding, and mucosal appearance. Each component could be scored 0–3. Patients were included if they had a score that was at least 4 but no more than 10.

Mucosal appearance could only be assessed at the time of sigmoidoscopy, so the researchers also used a modified disease activity index (mDAI) that excluded mucosal appearance and ranged from 0 to 9 points.

At baseline, patients had a complete DAI calculated and then were randomized. Follow-up occurred at weeks 4, 8, and 12. At weeks 4 and 8, an mDAI was calculated, and at week 12 (study end point) a complete DAI was calculated. During the course of the study, patients were not allowed to increase their usual medications, nor were corticosteroids tapered.

Clinical remission was defined as a final DAI score of no more than 2. Endoscopic remission required a final DAI score of less than 2 and a mucosal appearance score of 0. The researchers defined response as a reduction in DAI score of at least 3 points, as this definition has been used in other trials. Response at weeks 4 and 6 was defined as a reduction from baseline of at least 2 points on the mDAI.

With the more stringent definition of response, more patients on rosiglitazone (37%) responded than patients in the placebo group (13%). Likewise, more patients on rosiglitazone had clinical remission—17%, compared with 2% in the placebo group. In terms of endoscopic remission, 8% in the rosiglitazone group met the criteria, compared with 2% in the placebo group; this difference was not statistically significant.

In terms of adverse events, lower extremity edema was significantly more common among patients on rosiglitazone—17% vs. 2% for placebo. Patients were more likely to withdraw early because of worsening disease if they were in the placebo arm: 11 patients vs. 4 in the rosiglitazone arm.

In a post hoc analysis, the researchers excluded patients with lower extremity edema during the course of the study. They were concerned that such edema could have unmasked the treatment assignments for these patients because this is a common side effect of rosiglitazone. However, “the results are almost identical to those from our primary intention to treat analysis,” Dr. Lewis said.

Rosaglitazone has recently made headlines, based on an analysis of 42 published and unpublished randomized trials showing that patients who received rosiglitazone were 43% more likely to have an MI than were patients who received either an active comparator drug or placebo during the course of 24–52 weeks of treatment (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

In a separate study of more than 33,000 patients with type 2 diabetes, researchers found that the incidence of hospitalizations for heart attack and/or for coronary revascularization for patients on rosiglitazone was the same as for patients on metformin or sulfonylurea (Pharmacoepidemiol. Drug Saf. 2007 [Epub doi: 10.1002/pds.1443]). The research involved an observational cohort study from a large U.S. managed care database and was commissioned by Glaxo-SmithKline. The study populations were matched to ensure that the cohort groups were similar in terms of their baseline risk factors for cardiovascular disease. Patients were followed for an average of slightly over a year.

In May, the Food and Drug Administration issued a safety alert regarding potential safety issues related to the drug. The agency noted that its “analyses of all available data are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies.”

WASHINGTON — Rosiglitazone shows some promise in reducing ulcerative colitis activity and may offer an alternative to conventional therapy for patients who fail to respond to the latter approach or can't tolerate it, said Dr. James D. Lewis at the annual Digestive Disease Week.

Rosiglitazone (Avandia) reduced disease activity significantly, compared with placebo in patients with mild to moderate ulcerative colitis activity.

In the study of 105 patients, 44% of those taking rosiglitazone achieved clinical remission—defined as at least a 2-point drop in the disease activity index at 12 weeks—compared with 23% of those on placebo.

Fifty-two patients were randomized to receive 4 mg rosiglitazone twice daily, and 53 received placebo. Most of the patients were male (79%), with an average age of 44 years.

“Rosiglitazone may represent a novel approach to the treatment of mild to moderately active ulcerative colitis and conceivably has a role in those patients who fail to respond to or are unable to tolerate 5-aminosalicylic acid therapy,” said Dr. Lewis, associate director of the University of Pennsylvania Health System's Inflammatory Bowel Disease Program in Philadelphia.

Dr. Lewis disclosed that he has received grants and research support from GlaxoSmithKline, maker of Avandia. The company also supplied rosiglitazone for this study.

Patients had to have been treated with at least 2 g/day of 5-aminosalicylic acid for at least 4 weeks prior to randomization, or they had to have documented intolerance to this therapy. Corticosteroids were allowed, as long as the patient was on a stable dose for at least 4 weeks or taking no more than 20 mg/day of prednisone or the equivalent.

Immunomodulators (azathioprine and 6-mercaptopurine) were also allowed if the patient had been treated with these for at least 4 months and was on a stable dose for at least 2 months. Rectal therapies were also allowed, as long as the dose had been stable for at least 2 weeks prior to randomization.

Patients were excluded if they had diabetes mellitus requiring treatment with a hypoglycemic agent or had New York Heart Association class III or IV heart failure. Patients were also excluded if they were taking cyclosporine, anti-tumor necrosis factor-α drugs, or methotrexate within 2 months of the study.

The researchers used a modified version of the Sutherland and Mayo disease activity indices to assess disease activity. This index (DAI) included four components: stool frequency, physician global assessment, rectal bleeding, and mucosal appearance. Each component could be scored 0–3. Patients were included if they had a score that was at least 4 but no more than 10.

Mucosal appearance could only be assessed at the time of sigmoidoscopy, so the researchers also used a modified disease activity index (mDAI) that excluded mucosal appearance and ranged from 0 to 9 points.

At baseline, patients had a complete DAI calculated and then were randomized. Follow-up occurred at weeks 4, 8, and 12. At weeks 4 and 8, an mDAI was calculated, and at week 12 (study end point) a complete DAI was calculated. During the course of the study, patients were not allowed to increase their usual medications, nor were corticosteroids tapered.

Clinical remission was defined as a final DAI score of no more than 2. Endoscopic remission required a final DAI score of less than 2 and a mucosal appearance score of 0. The researchers defined response as a reduction in DAI score of at least 3 points, as this definition has been used in other trials. Response at weeks 4 and 6 was defined as a reduction from baseline of at least 2 points on the mDAI.

With the more stringent definition of response, more patients on rosiglitazone (37%) responded than patients in the placebo group (13%). Likewise, more patients on rosiglitazone had clinical remission—17%, compared with 2% in the placebo group. In terms of endoscopic remission, 8% in the rosiglitazone group met the criteria, compared with 2% in the placebo group; this difference was not statistically significant.

In terms of adverse events, lower extremity edema was significantly more common among patients on rosiglitazone—17% vs. 2% for placebo. Patients were more likely to withdraw early because of worsening disease if they were in the placebo arm: 11 patients vs. 4 in the rosiglitazone arm.

In a post hoc analysis, the researchers excluded patients with lower extremity edema during the course of the study. They were concerned that such edema could have unmasked the treatment assignments for these patients because this is a common side effect of rosiglitazone. However, “the results are almost identical to those from our primary intention to treat analysis,” Dr. Lewis said.

Rosaglitazone has recently made headlines, based on an analysis of 42 published and unpublished randomized trials showing that patients who received rosiglitazone were 43% more likely to have an MI than were patients who received either an active comparator drug or placebo during the course of 24–52 weeks of treatment (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

In a separate study of more than 33,000 patients with type 2 diabetes, researchers found that the incidence of hospitalizations for heart attack and/or for coronary revascularization for patients on rosiglitazone was the same as for patients on metformin or sulfonylurea (Pharmacoepidemiol. Drug Saf. 2007 [Epub doi: 10.1002/pds.1443]). The research involved an observational cohort study from a large U.S. managed care database and was commissioned by Glaxo-SmithKline. The study populations were matched to ensure that the cohort groups were similar in terms of their baseline risk factors for cardiovascular disease. Patients were followed for an average of slightly over a year.

In May, the Food and Drug Administration issued a safety alert regarding potential safety issues related to the drug. The agency noted that its “analyses of all available data are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies.”

WASHINGTON — Rosiglitazone shows some promise in reducing ulcerative colitis activity and may offer an alternative to conventional therapy for patients who fail to respond to the latter approach or can't tolerate it, said Dr. James D. Lewis at the annual Digestive Disease Week.

Rosiglitazone (Avandia) reduced disease activity significantly, compared with placebo in patients with mild to moderate ulcerative colitis activity.

In the study of 105 patients, 44% of those taking rosiglitazone achieved clinical remission—defined as at least a 2-point drop in the disease activity index at 12 weeks—compared with 23% of those on placebo.

Fifty-two patients were randomized to receive 4 mg rosiglitazone twice daily, and 53 received placebo. Most of the patients were male (79%), with an average age of 44 years.

“Rosiglitazone may represent a novel approach to the treatment of mild to moderately active ulcerative colitis and conceivably has a role in those patients who fail to respond to or are unable to tolerate 5-aminosalicylic acid therapy,” said Dr. Lewis, associate director of the University of Pennsylvania Health System's Inflammatory Bowel Disease Program in Philadelphia.

Dr. Lewis disclosed that he has received grants and research support from GlaxoSmithKline, maker of Avandia. The company also supplied rosiglitazone for this study.

Patients had to have been treated with at least 2 g/day of 5-aminosalicylic acid for at least 4 weeks prior to randomization, or they had to have documented intolerance to this therapy. Corticosteroids were allowed, as long as the patient was on a stable dose for at least 4 weeks or taking no more than 20 mg/day of prednisone or the equivalent.

Immunomodulators (azathioprine and 6-mercaptopurine) were also allowed if the patient had been treated with these for at least 4 months and was on a stable dose for at least 2 months. Rectal therapies were also allowed, as long as the dose had been stable for at least 2 weeks prior to randomization.

Patients were excluded if they had diabetes mellitus requiring treatment with a hypoglycemic agent or had New York Heart Association class III or IV heart failure. Patients were also excluded if they were taking cyclosporine, anti-tumor necrosis factor-α drugs, or methotrexate within 2 months of the study.

The researchers used a modified version of the Sutherland and Mayo disease activity indices to assess disease activity. This index (DAI) included four components: stool frequency, physician global assessment, rectal bleeding, and mucosal appearance. Each component could be scored 0–3. Patients were included if they had a score that was at least 4 but no more than 10.

Mucosal appearance could only be assessed at the time of sigmoidoscopy, so the researchers also used a modified disease activity index (mDAI) that excluded mucosal appearance and ranged from 0 to 9 points.

At baseline, patients had a complete DAI calculated and then were randomized. Follow-up occurred at weeks 4, 8, and 12. At weeks 4 and 8, an mDAI was calculated, and at week 12 (study end point) a complete DAI was calculated. During the course of the study, patients were not allowed to increase their usual medications, nor were corticosteroids tapered.

Clinical remission was defined as a final DAI score of no more than 2. Endoscopic remission required a final DAI score of less than 2 and a mucosal appearance score of 0. The researchers defined response as a reduction in DAI score of at least 3 points, as this definition has been used in other trials. Response at weeks 4 and 6 was defined as a reduction from baseline of at least 2 points on the mDAI.

With the more stringent definition of response, more patients on rosiglitazone (37%) responded than patients in the placebo group (13%). Likewise, more patients on rosiglitazone had clinical remission—17%, compared with 2% in the placebo group. In terms of endoscopic remission, 8% in the rosiglitazone group met the criteria, compared with 2% in the placebo group; this difference was not statistically significant.

In terms of adverse events, lower extremity edema was significantly more common among patients on rosiglitazone—17% vs. 2% for placebo. Patients were more likely to withdraw early because of worsening disease if they were in the placebo arm: 11 patients vs. 4 in the rosiglitazone arm.

In a post hoc analysis, the researchers excluded patients with lower extremity edema during the course of the study. They were concerned that such edema could have unmasked the treatment assignments for these patients because this is a common side effect of rosiglitazone. However, “the results are almost identical to those from our primary intention to treat analysis,” Dr. Lewis said.

Rosaglitazone has recently made headlines, based on an analysis of 42 published and unpublished randomized trials showing that patients who received rosiglitazone were 43% more likely to have an MI than were patients who received either an active comparator drug or placebo during the course of 24–52 weeks of treatment (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

In a separate study of more than 33,000 patients with type 2 diabetes, researchers found that the incidence of hospitalizations for heart attack and/or for coronary revascularization for patients on rosiglitazone was the same as for patients on metformin or sulfonylurea (Pharmacoepidemiol. Drug Saf. 2007 [Epub doi: 10.1002/pds.1443]). The research involved an observational cohort study from a large U.S. managed care database and was commissioned by Glaxo-SmithKline. The study populations were matched to ensure that the cohort groups were similar in terms of their baseline risk factors for cardiovascular disease. Patients were followed for an average of slightly over a year.

In May, the Food and Drug Administration issued a safety alert regarding potential safety issues related to the drug. The agency noted that its “analyses of all available data are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies.”

WASHINGTON — Older patients with pain resulting from diabetic peripheral neuropathy are more likely to be treated with fewer categories of pain medications than are younger patients, according to a poster presented at the annual meeting of the American Pain Society.

Roughly half (51%) of patients aged 65 years or older with diabetic peripheral neuropathy (DPN) were prescribed only one category of drugs on average to treat their pain each year, compared with 40% of those younger than age 65 years, wrote Stephen Able, Ph.D., a researcher at Eli Lilly & Co., and his colleagues. Lilly makes Cymbalta (duloxetine), which has Food and Drug Administration approval for the treatment of pain associated with DPN.

The researchers used pharmacy data from the Department of Veterans Affairs' National Pharmacy Benefits Management Program as well as VA administrative data, including inpatient and outpatient files from Oct. 1, 2001, through Sept. 20, 2004. Patients were included if they had a diagnosis of diabetes (based on ICD codes) or a pharmacy claim for a diabetic medication. Patients also had to have a diagnosis of neuropathy and an outpatient prescription drug claim for medication recommended for the management of pain.

Patients were excluded if they had a diagnosis of schizophrenia, bipolar disorder, psychosis, depression, or anxiety.

In particular, the researchers looked at the numbers of different pain-related medication categories used to treat patients with DPN annually and the percentage of patients with DPN using medications from each category. Categories included anticonvulsants, antidepressants, short- and long-acting narcotics, and nonnarcotic analgesics.

In fiscal years 2002, 2003, and 2004, the analysis included 52,947 patients, 54,924 patients, and 58,145 patients, respectively.

Patients 65 years of age and older were less likely to receive a prescription for more than one category of medications. On average, 30% of those 65 years of age and older had prescriptions for two categories of pain medication each year, compared with 32% of those younger than 65 years. Additionally, 13% of those aged 65 and older had prescriptions for three categories of medication, compared with 19% of those younger than 65.

The researchers hypothesized that the differences in prescribing patterns between the age cohorts may reflect different strategies for managing pain in older patients with DPN as a result of greater concerns about drug tolerability in this age group; differences in the manifestations of pain associated with DPN as the condition progresses; and/or changes in patient perception of pain as they age.

Overall, nonnarcotic analgesics (COX-2 inhibitors, NSAIDs, and others) were the most commonly prescribed category of pain-related medications in this population—70% or more in each of the study years.

However, the use of long-acting narcotics (tramadol, oxycodone, and others) doubled during the study period, up from 7% overall in fiscal year 2002 to 14% overall in fiscal year 2004. The use of anticonvulsants (gabapentin and others) increased steadily in both age groups with time, although more so for the younger cohort.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Older patients with pain resulting from diabetic peripheral neuropathy are more likely to be treated with fewer categories of pain medications than are younger patients, according to a poster presented at the annual meeting of the American Pain Society.

Roughly half (51%) of patients aged 65 years or older with diabetic peripheral neuropathy (DPN) were prescribed only one category of drugs on average to treat their pain each year, compared with 40% of those younger than age 65 years, wrote Stephen Able, Ph.D., a researcher at Eli Lilly & Co., and his colleagues. Lilly makes Cymbalta (duloxetine), which has Food and Drug Administration approval for the treatment of pain associated with DPN.

The researchers used pharmacy data from the Department of Veterans Affairs' National Pharmacy Benefits Management Program as well as VA administrative data, including inpatient and outpatient files from Oct. 1, 2001, through Sept. 20, 2004. Patients were included if they had a diagnosis of diabetes (based on ICD codes) or a pharmacy claim for a diabetic medication. Patients also had to have a diagnosis of neuropathy and an outpatient prescription drug claim for medication recommended for the management of pain.

Patients were excluded if they had a diagnosis of schizophrenia, bipolar disorder, psychosis, depression, or anxiety.

In particular, the researchers looked at the numbers of different pain-related medication categories used to treat patients with DPN annually and the percentage of patients with DPN using medications from each category. Categories included anticonvulsants, antidepressants, short- and long-acting narcotics, and nonnarcotic analgesics.

In fiscal years 2002, 2003, and 2004, the analysis included 52,947 patients, 54,924 patients, and 58,145 patients, respectively.

Patients 65 years of age and older were less likely to receive a prescription for more than one category of medications. On average, 30% of those 65 years of age and older had prescriptions for two categories of pain medication each year, compared with 32% of those younger than 65 years. Additionally, 13% of those aged 65 and older had prescriptions for three categories of medication, compared with 19% of those younger than 65.

The researchers hypothesized that the differences in prescribing patterns between the age cohorts may reflect different strategies for managing pain in older patients with DPN as a result of greater concerns about drug tolerability in this age group; differences in the manifestations of pain associated with DPN as the condition progresses; and/or changes in patient perception of pain as they age.

Overall, nonnarcotic analgesics (COX-2 inhibitors, NSAIDs, and others) were the most commonly prescribed category of pain-related medications in this population—70% or more in each of the study years.

However, the use of long-acting narcotics (tramadol, oxycodone, and others) doubled during the study period, up from 7% overall in fiscal year 2002 to 14% overall in fiscal year 2004. The use of anticonvulsants (gabapentin and others) increased steadily in both age groups with time, although more so for the younger cohort.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Older patients with pain resulting from diabetic peripheral neuropathy are more likely to be treated with fewer categories of pain medications than are younger patients, according to a poster presented at the annual meeting of the American Pain Society.

Roughly half (51%) of patients aged 65 years or older with diabetic peripheral neuropathy (DPN) were prescribed only one category of drugs on average to treat their pain each year, compared with 40% of those younger than age 65 years, wrote Stephen Able, Ph.D., a researcher at Eli Lilly & Co., and his colleagues. Lilly makes Cymbalta (duloxetine), which has Food and Drug Administration approval for the treatment of pain associated with DPN.

The researchers used pharmacy data from the Department of Veterans Affairs' National Pharmacy Benefits Management Program as well as VA administrative data, including inpatient and outpatient files from Oct. 1, 2001, through Sept. 20, 2004. Patients were included if they had a diagnosis of diabetes (based on ICD codes) or a pharmacy claim for a diabetic medication. Patients also had to have a diagnosis of neuropathy and an outpatient prescription drug claim for medication recommended for the management of pain.

Patients were excluded if they had a diagnosis of schizophrenia, bipolar disorder, psychosis, depression, or anxiety.

In particular, the researchers looked at the numbers of different pain-related medication categories used to treat patients with DPN annually and the percentage of patients with DPN using medications from each category. Categories included anticonvulsants, antidepressants, short- and long-acting narcotics, and nonnarcotic analgesics.

In fiscal years 2002, 2003, and 2004, the analysis included 52,947 patients, 54,924 patients, and 58,145 patients, respectively.

Patients 65 years of age and older were less likely to receive a prescription for more than one category of medications. On average, 30% of those 65 years of age and older had prescriptions for two categories of pain medication each year, compared with 32% of those younger than 65 years. Additionally, 13% of those aged 65 and older had prescriptions for three categories of medication, compared with 19% of those younger than 65.

The researchers hypothesized that the differences in prescribing patterns between the age cohorts may reflect different strategies for managing pain in older patients with DPN as a result of greater concerns about drug tolerability in this age group; differences in the manifestations of pain associated with DPN as the condition progresses; and/or changes in patient perception of pain as they age.

Overall, nonnarcotic analgesics (COX-2 inhibitors, NSAIDs, and others) were the most commonly prescribed category of pain-related medications in this population—70% or more in each of the study years.

However, the use of long-acting narcotics (tramadol, oxycodone, and others) doubled during the study period, up from 7% overall in fiscal year 2002 to 14% overall in fiscal year 2004. The use of anticonvulsants (gabapentin and others) increased steadily in both age groups with time, although more so for the younger cohort.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Risk factors for fracture in women with coronary heart disease or at increased risk for coronary heart disease do not predict the likelihood that treatment with raloxifene (Evista) will reduce the incidence of clinical vertebral or nonvertebral fractures.

The findings are derived from a secondary data analysis of women enrolled in the Raloxifene Use for the Heart (RUTH) study presented at an international symposium sponsored by the National Osteoporosis Foundation.

In the main study, 5,057 postmenopausal women treated with raloxifene (60 mg/day) had a reduced incidence of clinical vertebral fractures, compared with 5,044 women on placebo. The drug had no effect on overall incidence of nonvertebral fractures, said Dr. Jane A. Cauley, vice chair for research and professor of epidemiology at the University of Pittsburgh, who presented the findings on behalf of her colleague Dr. Kristine E. Ensrud of the University of Minnesota, Minneapolis.

The women were selected for the RUTH study because they had established coronary heart disease (CHD) or were at elevated risk for CHD, not because they were at risk for fracture. “We wanted to explore whether the effect of raloxifene in this population differed by risk factors for osteoporosis,” said Dr. Cauley, who disclosed that she has significant financial relationships with several pharmaceutical companies, including Eli Lilly & Co., which makes Evista and supported the study.

For the study, the women had to be at least 55 years old and postmenopausal for at least 1 year. The women had either an office visit or a telephone contact biannually. Fracture risk factors were assessed at baseline, but bone mineral density was not measured. Clinical vertebral and nonvertebral fractures were ascertained at each biannual visit or telephone contact and were confirmed by x-ray or medical records. The women were followed for an average of 5.6 years.

Risk factors for fracture included older age, smoking, lack of exercise, prior fractures since the age of 50, family history of hip fracture, diabetes, and certain medications (including hormones, thyroid hormone, and statins). Women were also assessed for body mass index (BMI) and were asked about weight loss in the previous year.

The average age for both the treatment group and the placebo group was 68 years, and women older than 70 years accounted for 39%. The women were predominantly white (84% in both groups). About 6% of women in each group had a history of a fracture, whereas almost 10% in each group had a family history of fracture. About 20% of women in both groups had a history of hormone therapy. Both groups had an average BMI of 29 kg/m2.

The final regression model for nonvertebral fractures included older age, prior fracture history, and family history of hip fracture. The final regression model for clinical vertebral fractures included age and prior use of hormone therapy.

“There was no difference in the effect of raloxifene on nonvertebral fractures for any of the [individual] risk factors that we examined,” Dr. Cauley said. Likewise, whereas there was an overall reduction in clinical vertebral fractures for women on raloxifene, the reduction in treated women was similar regardless of which risk factor was assessed.

In the original study, researchers found no significant difference between the two groups in the primary end point of incidence of death from coronary causes, nonfatal MI, or hospitalization for acute coronary syndrome.

Raloxifene did reduce the incidence of invasive breast cancer (hazard ratio 0.56), primarily because of a reduction in estrogen receptor-positive invasive breast cancer, another primary end point (N. Engl. J. Med. 2006;355:125–37).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Risk factors for fracture in women with coronary heart disease or at increased risk for coronary heart disease do not predict the likelihood that treatment with raloxifene (Evista) will reduce the incidence of clinical vertebral or nonvertebral fractures.

The findings are derived from a secondary data analysis of women enrolled in the Raloxifene Use for the Heart (RUTH) study presented at an international symposium sponsored by the National Osteoporosis Foundation.

In the main study, 5,057 postmenopausal women treated with raloxifene (60 mg/day) had a reduced incidence of clinical vertebral fractures, compared with 5,044 women on placebo. The drug had no effect on overall incidence of nonvertebral fractures, said Dr. Jane A. Cauley, vice chair for research and professor of epidemiology at the University of Pittsburgh, who presented the findings on behalf of her colleague Dr. Kristine E. Ensrud of the University of Minnesota, Minneapolis.

The women were selected for the RUTH study because they had established coronary heart disease (CHD) or were at elevated risk for CHD, not because they were at risk for fracture. “We wanted to explore whether the effect of raloxifene in this population differed by risk factors for osteoporosis,” said Dr. Cauley, who disclosed that she has significant financial relationships with several pharmaceutical companies, including Eli Lilly & Co., which makes Evista and supported the study.

For the study, the women had to be at least 55 years old and postmenopausal for at least 1 year. The women had either an office visit or a telephone contact biannually. Fracture risk factors were assessed at baseline, but bone mineral density was not measured. Clinical vertebral and nonvertebral fractures were ascertained at each biannual visit or telephone contact and were confirmed by x-ray or medical records. The women were followed for an average of 5.6 years.

Risk factors for fracture included older age, smoking, lack of exercise, prior fractures since the age of 50, family history of hip fracture, diabetes, and certain medications (including hormones, thyroid hormone, and statins). Women were also assessed for body mass index (BMI) and were asked about weight loss in the previous year.

The average age for both the treatment group and the placebo group was 68 years, and women older than 70 years accounted for 39%. The women were predominantly white (84% in both groups). About 6% of women in each group had a history of a fracture, whereas almost 10% in each group had a family history of fracture. About 20% of women in both groups had a history of hormone therapy. Both groups had an average BMI of 29 kg/m2.

The final regression model for nonvertebral fractures included older age, prior fracture history, and family history of hip fracture. The final regression model for clinical vertebral fractures included age and prior use of hormone therapy.

“There was no difference in the effect of raloxifene on nonvertebral fractures for any of the [individual] risk factors that we examined,” Dr. Cauley said. Likewise, whereas there was an overall reduction in clinical vertebral fractures for women on raloxifene, the reduction in treated women was similar regardless of which risk factor was assessed.

In the original study, researchers found no significant difference between the two groups in the primary end point of incidence of death from coronary causes, nonfatal MI, or hospitalization for acute coronary syndrome.

Raloxifene did reduce the incidence of invasive breast cancer (hazard ratio 0.56), primarily because of a reduction in estrogen receptor-positive invasive breast cancer, another primary end point (N. Engl. J. Med. 2006;355:125–37).

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Risk factors for fracture in women with coronary heart disease or at increased risk for coronary heart disease do not predict the likelihood that treatment with raloxifene (Evista) will reduce the incidence of clinical vertebral or nonvertebral fractures.

The findings are derived from a secondary data analysis of women enrolled in the Raloxifene Use for the Heart (RUTH) study presented at an international symposium sponsored by the National Osteoporosis Foundation.

In the main study, 5,057 postmenopausal women treated with raloxifene (60 mg/day) had a reduced incidence of clinical vertebral fractures, compared with 5,044 women on placebo. The drug had no effect on overall incidence of nonvertebral fractures, said Dr. Jane A. Cauley, vice chair for research and professor of epidemiology at the University of Pittsburgh, who presented the findings on behalf of her colleague Dr. Kristine E. Ensrud of the University of Minnesota, Minneapolis.

The women were selected for the RUTH study because they had established coronary heart disease (CHD) or were at elevated risk for CHD, not because they were at risk for fracture. “We wanted to explore whether the effect of raloxifene in this population differed by risk factors for osteoporosis,” said Dr. Cauley, who disclosed that she has significant financial relationships with several pharmaceutical companies, including Eli Lilly & Co., which makes Evista and supported the study.

For the study, the women had to be at least 55 years old and postmenopausal for at least 1 year. The women had either an office visit or a telephone contact biannually. Fracture risk factors were assessed at baseline, but bone mineral density was not measured. Clinical vertebral and nonvertebral fractures were ascertained at each biannual visit or telephone contact and were confirmed by x-ray or medical records. The women were followed for an average of 5.6 years.

Risk factors for fracture included older age, smoking, lack of exercise, prior fractures since the age of 50, family history of hip fracture, diabetes, and certain medications (including hormones, thyroid hormone, and statins). Women were also assessed for body mass index (BMI) and were asked about weight loss in the previous year.

The average age for both the treatment group and the placebo group was 68 years, and women older than 70 years accounted for 39%. The women were predominantly white (84% in both groups). About 6% of women in each group had a history of a fracture, whereas almost 10% in each group had a family history of fracture. About 20% of women in both groups had a history of hormone therapy. Both groups had an average BMI of 29 kg/m2.

The final regression model for nonvertebral fractures included older age, prior fracture history, and family history of hip fracture. The final regression model for clinical vertebral fractures included age and prior use of hormone therapy.

“There was no difference in the effect of raloxifene on nonvertebral fractures for any of the [individual] risk factors that we examined,” Dr. Cauley said. Likewise, whereas there was an overall reduction in clinical vertebral fractures for women on raloxifene, the reduction in treated women was similar regardless of which risk factor was assessed.

In the original study, researchers found no significant difference between the two groups in the primary end point of incidence of death from coronary causes, nonfatal MI, or hospitalization for acute coronary syndrome.

Raloxifene did reduce the incidence of invasive breast cancer (hazard ratio 0.56), primarily because of a reduction in estrogen receptor-positive invasive breast cancer, another primary end point (N. Engl. J. Med. 2006;355:125–37).

ELSEVIER GLOBAL MEDICAL NEWS