Patrice Wendling

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?” he said.

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with nonselective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?” he said.

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with nonselective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Recent events surrounding selective cyclooxygenase-2 inhibitors will have far-reaching implications for future drug trials, Gary S. Hoffman, M.D., said at a symposium sponsored by the American College of Rheumatology.

Drugs under investigation for chronic diseases such as arthritis will require longer trials and follow-up than in the past, in part because of their likely long-term use among the patients who need them.

“We can no longer endorse or not endorse these drugs based upon short-term studies, some of which have been as short as 6 weeks or 12 weeks and usually, certainly, less than a year,” said Dr. Hoffman, a member of the Food and Drug Administration's arthritis advisory committee.

NSAID trials now will include cardiovascular and thrombotic events among the adverse events they monitor.

But this raises questions as to whether there are other adverse events (AEs) such as cancer, autoimmune effects, or neurocognitive dysfunction that are beyond our current knowledge, said Dr. Hoffman, professor of medicine and chair of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

“Are we looking at this with blinders on because of recent events or are there other important AEs that we should also be casting a broader net for?” Dr. Hoffman asked.

“Perhaps there are increases in malignancies if you follow patients who take drug x, y, or z long enough. How long should those patients be studied in the context of randomized trials?” he said.

Although answers to these questions are lacking, it's obvious that closer premarket drug scrutiny will come at a greater cost, he said.

Forces such as the market, consumers, and the medical community will need to determine how cost-effectiveness will be measured, and ultimately who will pay.

New strategies need to be developed to make new drug studies cost effective, he said.

Ironically, it was adverse events associated with nonselective NSAIDs that drove the COX-2 market in the first place, he noted. Research suggests that as much as one-third of every dollar spent on NSAIDs goes to managing adverse events.

CHICAGO — Agility and perturbation exercises may enhance knee stability and function in patients with knee osteoarthritis, G. Kelley Fitzgerald, Ph.D., reported at a symposium sponsored by the American College of Rheumatology.

Knee instability is a common problem in knee osteoarthritis (OA) and affects physical function beyond what can be explained by knee pain and muscle weakness, said Dr. Fitzgerald, a physical therapist at the University of Pittsburgh.

In an study of 105 patients with knee OA, Dr. Fitzgerald found that 67 patients (64%) reported knee instability during daily living activities, and 47 (45%) reported that instability affects their physical function (Arthritis Rheum. 2004;51:941-6).

A gait analysis of 48 patients, led by colleague John D. Childs, Ph.D., found that those with knee OA had reduced knee flexion and extension movements and significant increases in muscle co-contractions during walking. The vastus lateralis, medial hamstrings, tibialis anterior, and medial gastrocnemius were activated about 1.5 times longer than the same muscles in controls (Clin. Biomech. [Bristol, Avon]2004;19:44-9).

To keep their knee stable, patients will often freeze their range of motion and simplify the steps necessary to perform a movement. The instability encourages them to resort to “primitive movement steps that limit their ability to perform higher level movements,” he said.

The combination of restricted knee movement and increased co-contractions puts additional stress on the joint, which in turn can accelerate OA disease progression.

The same interventions used to promote knee stability in athletes with knee ligament injuries can be modified to improve knee stability and function in people with knee OA, said Dr. Fitzgerald, who recommended adding agility and perturbation exercises twice a week to a traditional strengthening and stretching program.

Such modifications mean that agility drills with quick starts and stops are done at a walk rather than while running.

Perturbation techniques that for athletes involve a therapist rocking a roller or tilt board while the patient stands on it are done with the OA patient sitting down or while standing on both legs, rather than just one leg.

Exposing the patient's knee to such unpredictable and varied stresses can help expand movement patterns and boost the patient's confidence to perform more complex movements, making the patient more likely to stay active, he said.

The exercises have been tried in a handful of knee OA patients, who were then able to return to higher levels of physical activity with less pain and instability following rehabilitation.

In one case report, a 73-year-old woman with bilateral knee OA who complained of partial “giving away” at the knee during walking, was able to resume playing golf and tennis, in addition to feeling more confident while walking and going up and down stairs following rehabilitation. Her program consisted of a dozen sessions, held twice a week, of agility and perturbation exercises in addition to stretching, strengthening, and endurance exercises (Phys. Ther. 2002;82:372-82).

The results are “promising,” Dr. Fitzgerald said. The role of agility and perturbation training will be further evaluated in a forthcoming randomized trial of 160 patients with knee OA.

CHICAGO — Agility and perturbation exercises may enhance knee stability and function in patients with knee osteoarthritis, G. Kelley Fitzgerald, Ph.D., reported at a symposium sponsored by the American College of Rheumatology.

Knee instability is a common problem in knee osteoarthritis (OA) and affects physical function beyond what can be explained by knee pain and muscle weakness, said Dr. Fitzgerald, a physical therapist at the University of Pittsburgh.

In an study of 105 patients with knee OA, Dr. Fitzgerald found that 67 patients (64%) reported knee instability during daily living activities, and 47 (45%) reported that instability affects their physical function (Arthritis Rheum. 2004;51:941-6).

A gait analysis of 48 patients, led by colleague John D. Childs, Ph.D., found that those with knee OA had reduced knee flexion and extension movements and significant increases in muscle co-contractions during walking. The vastus lateralis, medial hamstrings, tibialis anterior, and medial gastrocnemius were activated about 1.5 times longer than the same muscles in controls (Clin. Biomech. [Bristol, Avon]2004;19:44-9).

To keep their knee stable, patients will often freeze their range of motion and simplify the steps necessary to perform a movement. The instability encourages them to resort to “primitive movement steps that limit their ability to perform higher level movements,” he said.

The combination of restricted knee movement and increased co-contractions puts additional stress on the joint, which in turn can accelerate OA disease progression.

The same interventions used to promote knee stability in athletes with knee ligament injuries can be modified to improve knee stability and function in people with knee OA, said Dr. Fitzgerald, who recommended adding agility and perturbation exercises twice a week to a traditional strengthening and stretching program.

Such modifications mean that agility drills with quick starts and stops are done at a walk rather than while running.

Perturbation techniques that for athletes involve a therapist rocking a roller or tilt board while the patient stands on it are done with the OA patient sitting down or while standing on both legs, rather than just one leg.

Exposing the patient's knee to such unpredictable and varied stresses can help expand movement patterns and boost the patient's confidence to perform more complex movements, making the patient more likely to stay active, he said.

The exercises have been tried in a handful of knee OA patients, who were then able to return to higher levels of physical activity with less pain and instability following rehabilitation.

In one case report, a 73-year-old woman with bilateral knee OA who complained of partial “giving away” at the knee during walking, was able to resume playing golf and tennis, in addition to feeling more confident while walking and going up and down stairs following rehabilitation. Her program consisted of a dozen sessions, held twice a week, of agility and perturbation exercises in addition to stretching, strengthening, and endurance exercises (Phys. Ther. 2002;82:372-82).

The results are “promising,” Dr. Fitzgerald said. The role of agility and perturbation training will be further evaluated in a forthcoming randomized trial of 160 patients with knee OA.

CHICAGO — Agility and perturbation exercises may enhance knee stability and function in patients with knee osteoarthritis, G. Kelley Fitzgerald, Ph.D., reported at a symposium sponsored by the American College of Rheumatology.

Knee instability is a common problem in knee osteoarthritis (OA) and affects physical function beyond what can be explained by knee pain and muscle weakness, said Dr. Fitzgerald, a physical therapist at the University of Pittsburgh.

In an study of 105 patients with knee OA, Dr. Fitzgerald found that 67 patients (64%) reported knee instability during daily living activities, and 47 (45%) reported that instability affects their physical function (Arthritis Rheum. 2004;51:941-6).

A gait analysis of 48 patients, led by colleague John D. Childs, Ph.D., found that those with knee OA had reduced knee flexion and extension movements and significant increases in muscle co-contractions during walking. The vastus lateralis, medial hamstrings, tibialis anterior, and medial gastrocnemius were activated about 1.5 times longer than the same muscles in controls (Clin. Biomech. [Bristol, Avon]2004;19:44-9).

To keep their knee stable, patients will often freeze their range of motion and simplify the steps necessary to perform a movement. The instability encourages them to resort to “primitive movement steps that limit their ability to perform higher level movements,” he said.

The combination of restricted knee movement and increased co-contractions puts additional stress on the joint, which in turn can accelerate OA disease progression.

The same interventions used to promote knee stability in athletes with knee ligament injuries can be modified to improve knee stability and function in people with knee OA, said Dr. Fitzgerald, who recommended adding agility and perturbation exercises twice a week to a traditional strengthening and stretching program.

Such modifications mean that agility drills with quick starts and stops are done at a walk rather than while running.

Perturbation techniques that for athletes involve a therapist rocking a roller or tilt board while the patient stands on it are done with the OA patient sitting down or while standing on both legs, rather than just one leg.

Exposing the patient's knee to such unpredictable and varied stresses can help expand movement patterns and boost the patient's confidence to perform more complex movements, making the patient more likely to stay active, he said.

The exercises have been tried in a handful of knee OA patients, who were then able to return to higher levels of physical activity with less pain and instability following rehabilitation.

In one case report, a 73-year-old woman with bilateral knee OA who complained of partial “giving away” at the knee during walking, was able to resume playing golf and tennis, in addition to feeling more confident while walking and going up and down stairs following rehabilitation. Her program consisted of a dozen sessions, held twice a week, of agility and perturbation exercises in addition to stretching, strengthening, and endurance exercises (Phys. Ther. 2002;82:372-82).

The results are “promising,” Dr. Fitzgerald said. The role of agility and perturbation training will be further evaluated in a forthcoming randomized trial of 160 patients with knee OA.

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

CHICAGO — Patients who receive intraarticular hyaluronan injections immediately after shoulder arthroscopy feel less postoperative pain and require less analgesia, compared with those who do not receive the injections, Lennard Funk, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis.

Hyaluronan, or hyaluronic acid, is the main hydrodynamic component of joint synovial fluid, conferring shock absorbing and lubricating qualities. It has long been used for the treatment of knee osteoarthritis.

Dr. Funk studied hyaluronan following shoulder arthroplasty after findings from a number of studies suggested that saline and other irrigation solutions impair articular cartilage metabolism.

In addition, studies have shown that joint immobilization reduces the production of endogenous hyaluronan.

Other evidence points to hyaluronan injections stimulating the endogenous production of hyaluronic acid postoperatively, and hindering the migration of inflammatory cells and mediators from blood vessels into the joint space.

“We were most impressed really with the pain relief effect [postoperatively],” Dr. Funk said at the congress, which was sponsored by the Osteoarthritis Research Society International. “The pain scores postoperatively were absolutely massive at 4 hours,” and use of the hyaluronan meant that “we could get them home earlier.” It's believed that hyaluronan coats the pain receptors, and also keeps the local anesthetic bupivacaine in the joint.

The 58 patients in the prospective study underwent arthroscopic subacromial decompression and were randomized into two groups.

At the end of surgery, the first group of 28 patients, mean age 50 years, was treated with 10 mL of hyaluronan (Viscoseal) and 10 mL of 0.5% bupivacaine injected into the subacromial bursa via an arthroscope.

The matched control group of 30 patients, mean age 48 years, received 20 mL of 0.5% bupivacaine only.

All procedures were performed or supervised by Dr. Funk of Hope Hospital in Manchester, England.

Four hours after surgery, only 3.5% of the hyaluronan group experienced severe pain, compared with 23% of the control group.

Of the patients in the hyaluronan group, 29% felt no pain, while none of the patients in the control group were pain free.

Of the patients in the hyaluronan group, 25% required no analgesia and 11% required opiates. All patients in the control group required analgesia and 33% required opiates.

Patients receiving hyaluronan were discharged twice as early as those not getting injections.

In a second study, Dr. Funk reported on the use of hyaluronan for inoperable arthritis of the shoulder in seven elderly patients: five with osteoarthritis, one with rheumatoid arthritis, and one with cuff arthropathy who received a course of three hyaluronan (Ostenil) injections into the glenohumeral joint at weekly intervals.

The Constant Score, which was used to assess clinical outcome, improved from a mean of 16 to 50 at 3 months post injection.

Visual analogue pain scores on a scale of 0-15 improved significantly from 12 to 5, respectively.

Patient satisfaction on a scale of 0-10 improved from 1 preinjection to 8 following the injections.

Dr. Funk said that there have been no reactions to either Viscoseal or Ostenil, which are manufactured by TRB Chemedica AG, Haar, Germany.

Dr. Funk said he has no financial interest in Viscoseal or Ostenil and did not receive funding for the studies presented at the congress, but he has received funding from the manufacturer for further research.

CHICAGO — Patients who receive intraarticular hyaluronan injections immediately after shoulder arthroscopy feel less postoperative pain and require less analgesia, compared with those who do not receive the injections, Lennard Funk, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis.

Hyaluronan, or hyaluronic acid, is the main hydrodynamic component of joint synovial fluid, conferring shock absorbing and lubricating qualities. It has long been used for the treatment of knee osteoarthritis.

Dr. Funk studied hyaluronan following shoulder arthroplasty after findings from a number of studies suggested that saline and other irrigation solutions impair articular cartilage metabolism.

In addition, studies have shown that joint immobilization reduces the production of endogenous hyaluronan.

Other evidence points to hyaluronan injections stimulating the endogenous production of hyaluronic acid postoperatively, and hindering the migration of inflammatory cells and mediators from blood vessels into the joint space.

“We were most impressed really with the pain relief effect [postoperatively],” Dr. Funk said at the congress, which was sponsored by the Osteoarthritis Research Society International. “The pain scores postoperatively were absolutely massive at 4 hours,” and use of the hyaluronan meant that “we could get them home earlier.” It's believed that hyaluronan coats the pain receptors, and also keeps the local anesthetic bupivacaine in the joint.

The 58 patients in the prospective study underwent arthroscopic subacromial decompression and were randomized into two groups.

At the end of surgery, the first group of 28 patients, mean age 50 years, was treated with 10 mL of hyaluronan (Viscoseal) and 10 mL of 0.5% bupivacaine injected into the subacromial bursa via an arthroscope.

The matched control group of 30 patients, mean age 48 years, received 20 mL of 0.5% bupivacaine only.

All procedures were performed or supervised by Dr. Funk of Hope Hospital in Manchester, England.

Four hours after surgery, only 3.5% of the hyaluronan group experienced severe pain, compared with 23% of the control group.

Of the patients in the hyaluronan group, 29% felt no pain, while none of the patients in the control group were pain free.

Of the patients in the hyaluronan group, 25% required no analgesia and 11% required opiates. All patients in the control group required analgesia and 33% required opiates.

Patients receiving hyaluronan were discharged twice as early as those not getting injections.

In a second study, Dr. Funk reported on the use of hyaluronan for inoperable arthritis of the shoulder in seven elderly patients: five with osteoarthritis, one with rheumatoid arthritis, and one with cuff arthropathy who received a course of three hyaluronan (Ostenil) injections into the glenohumeral joint at weekly intervals.

The Constant Score, which was used to assess clinical outcome, improved from a mean of 16 to 50 at 3 months post injection.

Visual analogue pain scores on a scale of 0-15 improved significantly from 12 to 5, respectively.

Patient satisfaction on a scale of 0-10 improved from 1 preinjection to 8 following the injections.

Dr. Funk said that there have been no reactions to either Viscoseal or Ostenil, which are manufactured by TRB Chemedica AG, Haar, Germany.

Dr. Funk said he has no financial interest in Viscoseal or Ostenil and did not receive funding for the studies presented at the congress, but he has received funding from the manufacturer for further research.

CHICAGO — Patients who receive intraarticular hyaluronan injections immediately after shoulder arthroscopy feel less postoperative pain and require less analgesia, compared with those who do not receive the injections, Lennard Funk, M.D., reported in a poster presentation at the 2004 World Congress on Osteoarthritis.

Hyaluronan, or hyaluronic acid, is the main hydrodynamic component of joint synovial fluid, conferring shock absorbing and lubricating qualities. It has long been used for the treatment of knee osteoarthritis.

Dr. Funk studied hyaluronan following shoulder arthroplasty after findings from a number of studies suggested that saline and other irrigation solutions impair articular cartilage metabolism.

In addition, studies have shown that joint immobilization reduces the production of endogenous hyaluronan.

Other evidence points to hyaluronan injections stimulating the endogenous production of hyaluronic acid postoperatively, and hindering the migration of inflammatory cells and mediators from blood vessels into the joint space.

“We were most impressed really with the pain relief effect [postoperatively],” Dr. Funk said at the congress, which was sponsored by the Osteoarthritis Research Society International. “The pain scores postoperatively were absolutely massive at 4 hours,” and use of the hyaluronan meant that “we could get them home earlier.” It's believed that hyaluronan coats the pain receptors, and also keeps the local anesthetic bupivacaine in the joint.

The 58 patients in the prospective study underwent arthroscopic subacromial decompression and were randomized into two groups.

At the end of surgery, the first group of 28 patients, mean age 50 years, was treated with 10 mL of hyaluronan (Viscoseal) and 10 mL of 0.5% bupivacaine injected into the subacromial bursa via an arthroscope.

The matched control group of 30 patients, mean age 48 years, received 20 mL of 0.5% bupivacaine only.

All procedures were performed or supervised by Dr. Funk of Hope Hospital in Manchester, England.

Four hours after surgery, only 3.5% of the hyaluronan group experienced severe pain, compared with 23% of the control group.

Of the patients in the hyaluronan group, 29% felt no pain, while none of the patients in the control group were pain free.

Of the patients in the hyaluronan group, 25% required no analgesia and 11% required opiates. All patients in the control group required analgesia and 33% required opiates.

Patients receiving hyaluronan were discharged twice as early as those not getting injections.

In a second study, Dr. Funk reported on the use of hyaluronan for inoperable arthritis of the shoulder in seven elderly patients: five with osteoarthritis, one with rheumatoid arthritis, and one with cuff arthropathy who received a course of three hyaluronan (Ostenil) injections into the glenohumeral joint at weekly intervals.

The Constant Score, which was used to assess clinical outcome, improved from a mean of 16 to 50 at 3 months post injection.

Visual analogue pain scores on a scale of 0-15 improved significantly from 12 to 5, respectively.

Patient satisfaction on a scale of 0-10 improved from 1 preinjection to 8 following the injections.

Dr. Funk said that there have been no reactions to either Viscoseal or Ostenil, which are manufactured by TRB Chemedica AG, Haar, Germany.

Dr. Funk said he has no financial interest in Viscoseal or Ostenil and did not receive funding for the studies presented at the congress, but he has received funding from the manufacturer for further research.

CHICAGO — Up to one-fourth of women with chronic pelvic pain also have piriformis or levator ani tenderness, according to a study presented by Dr. Frank Tu at a meeting sponsored by the International Pelvic Pain Society.

Musculoskeletal dysfunction—including tenderness and spasms of the levator ani and piriformis—has been reported as a treatable cause of chronic pelvic pain. The efficacy of treatments such as manual therapies, electrical stimulation, injected medications, and surgeries ranges from 20% to 90%, according to the literature, which is mostly comprised of case studies.

“Although musculoskeletal dysfunction is increasingly implicated as a cause of many pelvic pain conditions such as interstitial cystitis, we really don't have much information about the diagnosis, evaluation, treatment, and epidemiology of this particular condition,” Dr. Tu said. “This is the first study to look at the frequency of these disorders in a large referral clinic population.”

A retrospective study of 987 women referred to a pelvic pain clinic at the University of North Carolina, Chapel Hill, for chronic pelvic pain, found levator ani tenderness in 22% and piriformis tenderness in 13% of the 942 of patients evaluated for those conditions.

There were no differences between those with piriformis tenderness and those with levator ani tenderness in age (mean 30 years), pain duration, or sexual abuse history. Of the 987 women studied, 288 had a history of sexual abuse, said Dr. Tu, noting that the proportion of women with a history of abuse did not differ between the women with and without musculoskeletal dysfunction.

In all, 85% of patients had pain for at least 6 months, and most had daily pain. Two-thirds of the cohort had a diagnosis of depression, based on the Beck Depression Inventory.

A standardized abdominal exam was performed on all patients that included a single-digit intravaginal palpation of the levator ani and piriformis muscles, and either a Kegel contraction to identify the levators or an external hip rotation to identify the piriformis.

A visual analog score of 0-10 was assigned by the physician to rate the degree of clinically meaningful tenderness.

Piriformis and levator ani tenderness was positively associated with the number of painful abdominal-pelvic locations reported, pain associated with bowel movements, and higher Beck Depression Inventory and McGill Pain Questionnaire scores.

Patients with levator ani tenderness reported 4.6 pain locations, compared with 3.7 locations for those without such tenderness; patients with and without piriformis tenderness reported 4.6 and 3.8 pain locations, respectively.

Pain with bowel movements was reported by 372 study patients, including 51% of those with levator ani tenderness 50% of those with piriformis tenderness.

Levator ani tenderness was positively associated with a higher number of surgeries for pain. Of the 212 patients with levator ani tenderness, 23% had no previous surgeries, 61% had one-to-three surgeries, and 17% had more than three surgeries, compared with 30%, 60%, and 10%, respectively, of those without levator ani tenderness.

Neither condition was associated with pain that worsened with intercourse, although there was a trend toward a higher proportion with piriformis tenderness.

The data suggest that the prevalence of piriformis and levator ani tenderness may be increased among women with more intense chronic pelvic pain, said Dr. Tu, director of the division of chronic pelvic pain, department of ob.gyn., Evanston (Ill.) Hospital. A possible association with dyschezia also may exist.

CHICAGO — Up to one-fourth of women with chronic pelvic pain also have piriformis or levator ani tenderness, according to a study presented by Dr. Frank Tu at a meeting sponsored by the International Pelvic Pain Society.

Musculoskeletal dysfunction—including tenderness and spasms of the levator ani and piriformis—has been reported as a treatable cause of chronic pelvic pain. The efficacy of treatments such as manual therapies, electrical stimulation, injected medications, and surgeries ranges from 20% to 90%, according to the literature, which is mostly comprised of case studies.

“Although musculoskeletal dysfunction is increasingly implicated as a cause of many pelvic pain conditions such as interstitial cystitis, we really don't have much information about the diagnosis, evaluation, treatment, and epidemiology of this particular condition,” Dr. Tu said. “This is the first study to look at the frequency of these disorders in a large referral clinic population.”

A retrospective study of 987 women referred to a pelvic pain clinic at the University of North Carolina, Chapel Hill, for chronic pelvic pain, found levator ani tenderness in 22% and piriformis tenderness in 13% of the 942 of patients evaluated for those conditions.

There were no differences between those with piriformis tenderness and those with levator ani tenderness in age (mean 30 years), pain duration, or sexual abuse history. Of the 987 women studied, 288 had a history of sexual abuse, said Dr. Tu, noting that the proportion of women with a history of abuse did not differ between the women with and without musculoskeletal dysfunction.

In all, 85% of patients had pain for at least 6 months, and most had daily pain. Two-thirds of the cohort had a diagnosis of depression, based on the Beck Depression Inventory.

A standardized abdominal exam was performed on all patients that included a single-digit intravaginal palpation of the levator ani and piriformis muscles, and either a Kegel contraction to identify the levators or an external hip rotation to identify the piriformis.

A visual analog score of 0-10 was assigned by the physician to rate the degree of clinically meaningful tenderness.

Piriformis and levator ani tenderness was positively associated with the number of painful abdominal-pelvic locations reported, pain associated with bowel movements, and higher Beck Depression Inventory and McGill Pain Questionnaire scores.

Patients with levator ani tenderness reported 4.6 pain locations, compared with 3.7 locations for those without such tenderness; patients with and without piriformis tenderness reported 4.6 and 3.8 pain locations, respectively.

Pain with bowel movements was reported by 372 study patients, including 51% of those with levator ani tenderness 50% of those with piriformis tenderness.

Levator ani tenderness was positively associated with a higher number of surgeries for pain. Of the 212 patients with levator ani tenderness, 23% had no previous surgeries, 61% had one-to-three surgeries, and 17% had more than three surgeries, compared with 30%, 60%, and 10%, respectively, of those without levator ani tenderness.

Neither condition was associated with pain that worsened with intercourse, although there was a trend toward a higher proportion with piriformis tenderness.

The data suggest that the prevalence of piriformis and levator ani tenderness may be increased among women with more intense chronic pelvic pain, said Dr. Tu, director of the division of chronic pelvic pain, department of ob.gyn., Evanston (Ill.) Hospital. A possible association with dyschezia also may exist.

CHICAGO — Up to one-fourth of women with chronic pelvic pain also have piriformis or levator ani tenderness, according to a study presented by Dr. Frank Tu at a meeting sponsored by the International Pelvic Pain Society.

Musculoskeletal dysfunction—including tenderness and spasms of the levator ani and piriformis—has been reported as a treatable cause of chronic pelvic pain. The efficacy of treatments such as manual therapies, electrical stimulation, injected medications, and surgeries ranges from 20% to 90%, according to the literature, which is mostly comprised of case studies.

“Although musculoskeletal dysfunction is increasingly implicated as a cause of many pelvic pain conditions such as interstitial cystitis, we really don't have much information about the diagnosis, evaluation, treatment, and epidemiology of this particular condition,” Dr. Tu said. “This is the first study to look at the frequency of these disorders in a large referral clinic population.”

A retrospective study of 987 women referred to a pelvic pain clinic at the University of North Carolina, Chapel Hill, for chronic pelvic pain, found levator ani tenderness in 22% and piriformis tenderness in 13% of the 942 of patients evaluated for those conditions.

There were no differences between those with piriformis tenderness and those with levator ani tenderness in age (mean 30 years), pain duration, or sexual abuse history. Of the 987 women studied, 288 had a history of sexual abuse, said Dr. Tu, noting that the proportion of women with a history of abuse did not differ between the women with and without musculoskeletal dysfunction.

In all, 85% of patients had pain for at least 6 months, and most had daily pain. Two-thirds of the cohort had a diagnosis of depression, based on the Beck Depression Inventory.

A standardized abdominal exam was performed on all patients that included a single-digit intravaginal palpation of the levator ani and piriformis muscles, and either a Kegel contraction to identify the levators or an external hip rotation to identify the piriformis.

A visual analog score of 0-10 was assigned by the physician to rate the degree of clinically meaningful tenderness.

Piriformis and levator ani tenderness was positively associated with the number of painful abdominal-pelvic locations reported, pain associated with bowel movements, and higher Beck Depression Inventory and McGill Pain Questionnaire scores.

Patients with levator ani tenderness reported 4.6 pain locations, compared with 3.7 locations for those without such tenderness; patients with and without piriformis tenderness reported 4.6 and 3.8 pain locations, respectively.

Pain with bowel movements was reported by 372 study patients, including 51% of those with levator ani tenderness 50% of those with piriformis tenderness.

Levator ani tenderness was positively associated with a higher number of surgeries for pain. Of the 212 patients with levator ani tenderness, 23% had no previous surgeries, 61% had one-to-three surgeries, and 17% had more than three surgeries, compared with 30%, 60%, and 10%, respectively, of those without levator ani tenderness.

Neither condition was associated with pain that worsened with intercourse, although there was a trend toward a higher proportion with piriformis tenderness.

The data suggest that the prevalence of piriformis and levator ani tenderness may be increased among women with more intense chronic pelvic pain, said Dr. Tu, director of the division of chronic pelvic pain, department of ob.gyn., Evanston (Ill.) Hospital. A possible association with dyschezia also may exist.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“[Oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone, and Diane-35 (cyproterone acetate), which is not available in the United States, also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin may “top” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives, including seasonal pills taken only 4 times a year, have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most men and women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin. But she has prescribed them for use in girls as young as 13 years with acne.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

She suggested that physicians prescribe 6 months of OCs when treating acne to make sure patients are following up with their gynecologist and receiving regular breast exams. The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that either Yasmin or Diane-35 (cyproterone acetate/ethinyl estradiol) significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“[Oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone, and Diane-35 (cyproterone acetate), which is not available in the United States, also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin may “top” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives, including seasonal pills taken only 4 times a year, have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most men and women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin. But she has prescribed them for use in girls as young as 13 years with acne.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

She suggested that physicians prescribe 6 months of OCs when treating acne to make sure patients are following up with their gynecologist and receiving regular breast exams. The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that either Yasmin or Diane-35 (cyproterone acetate/ethinyl estradiol) significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

NEW ORLEANS — Oral contraceptives are a safe and effective treatment for acne but are best used as adjunct therapy, Julie C. Harper, M.D., reported at the annual meeting of the American Academy of Dermatology.

Topical retinoids such as adapalene, tazarotene, and tretinoin remain the first-line treatment for all grades of acne, followed by oral or topical antibiotics, and then hormonal therapy.

“[Oral contraceptives] are fabulous to add to your acne treatment, but they aren't stand-alone medications or first-line treatments,” Dr. Harper said.

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep (norethindrone acetate/ethinyl estradiol) have been approved by the Food and Drug Administration for the treatment of acne.

Newer contraceptives such as Yasmin, which contains the novel progestin drospirenone, and Diane-35 (cyproterone acetate), which is not available in the United States, also are effective, said Dr. Harper of the department of dermatology at the University of Alabama, Birmingham.

A recent study showed that Yasmin was superior to Ortho Tri-Cyclen in reducing the total number of skin lesions in women with mild to moderate acne vulgaris after 6 months, and was rated superior by investigators for its therapeutic effect (Cutis. 2004;74:123-30).

Yasmin may “top” the other OCs in treating acne, but the difference is not dramatic, Dr. Harper said. It may take several months to see an improvement in acne on Yasmin, and she recommends a minimum of 3 months of treatment.

Yasmin combines ethinyl estradiol and 3 mg of drospirenone, a spironolactone analogue that has antimineralocorticoid and antiandrogenic activity. Androgens stimulate sebaceous epithelial cell (sebocyte) differentiation and sebum production. Excess sebum is a key factor in the development of acne.

All combined oral contraceptives, including seasonal pills taken only 4 times a year, have the potential to improve acne because they increase sex hormone-binding globulin, thereby decreasing serum androgen. This is true even when a woman's serum levels are in the normal range.

Most men and women with acne have normal circulating levels of androgen hormones, she said, adding that scientists now suspect an end-organ hyperresponsiveness to androgens in patients with acne.

OCs are used most safely to treat acne in younger women who don't smoke, do not have a history of migraines, and are normotensive. Dr. Harper will not prescribe OCs to women who smoke, are aged 35 years or older, or on rifampin. But she has prescribed them for use in girls as young as 13 years with acne.

Spironolactone 50-100 mg is recommended for women who aren't candidates for OCs and have failed conservative treatments.

She suggested that physicians prescribe 6 months of OCs when treating acne to make sure patients are following up with their gynecologist and receiving regular breast exams. The relative risk of breast cancer is 1.24 times higher in current OC users, she said.

The relative risk of stroke is 2.5 times higher in current contraceptive users, although there has been no evidence that either Yasmin or Diane-35 (cyproterone acetate/ethinyl estradiol) significantly increases thrombolytic events, compared with other OCs, Dr. Harper said.

CHICAGO — Kyphoplasty appears associated with a low rate of complications in patients with osteoporotic or osteolytic vertebral compression fractures, according to the results of a prospective study presented at the annual meeting of the North American Spine Society.

Functional disability also improves over the long run. Such findings emerge just as use of the technique for treating vertebral compression fractures is gaining in popularity and questions about its safety and efficacy are being raised.

According to a review of the literature and complications reported to the Food and Drug Administration, the main safety concerns involve reactions to the use of acrylic (polymethylmethacrylate) bone cement, including hypotension and in some cases death, especially when multiple vertebral levels are treated in one setting. The procedure has also been linked with an increased rate of pedicle fracture and cord compression (J. Vasc. Interv. Radiol. 2004;15:1185-92).

In addition, a retrospective chart review involving 38 consecutive patients indicated that the risk of subsequent fracture in adjacent vertebrae was higher after kyphoplasty than in untreated patients, suggesting that kyphoplasty may shift stress to adjacent vertebrae (Spine 2004;29:2270-6).

In this latest prospective study, a total of 329 consecutive patients with osteoporotic or osteolytic vertebral compression fractures underwent 917 kyphoplasty procedures. Surgeries were performed at the Cleveland Clinic, said Isador Lieberman, M.D., director of its minimally invasive surgery center and center for advanced skills training, and the study's lead investigator.

The rate of subsequent compression fractures in the osteoporotic patients was 11.5%, which is almost half the natural history rate, reported Dr. Lieberman, who is one of the developers of kyphoplasty and is a paid consultant to Kyphon Inc., which manufacturers the inflatable bone tamp.

Study participants were a mean age of 69.2 years and 209 were female. All patients had painful compression fractures secondary to primary osteoporosis (228 patients), multiple myeloma (80 patients), or other malignancy (21 patients) that was refractory to nonoperative treatment.

The levels treated ranged from T3 to L5, with about half of the procedures at the thoracolumbar junction. Local anesthesia was used in 32 procedures. The average length of hospital stay was 1 day, with a range of 0.5 to 9 days.

Complications included cement leaks, which occurred in 24 patients, but none were clinically significant. One patient suffered a perioperative myocardial infarction. There were no neurologic complications or cement reactions, said Dr. Lieberman, who called the issue of such reactions as reported in the literature “misleading and erroneous.”

Short Form-36 (SF-36) health survey data pre- and post operative were available on 237 patients, with a mean of 55 weeks' follow-up.

SF-36 scores improved significantly in every category except general health, which was unchanged. Measures of physical functioning improved on a 0-to-100 scale from 22 to 36, bodily pain from 22 to 42, vitality from 31 to 41, social functioning from 38 to 61, emotional well-being from 55 to 66, and mental health from 63 to 68. “We advocate the use of kyphoplasty [as an] early intervention for osteoporotic and osteolytic vertebral compression fractures to prevent pain and progressive kyphosis,” said study investigator A. Jay Khanna, M.D.

Overall, Oswestry Disability Index scores improved from 48 to 34.3 (−13.7) and such improvements were similar for patients with osteoporosis and myeloma, (−15.8 and −14.5, respectively), said Dr. Khanna, who conducted the study at the Cleveland Clinic but is now at Johns Hopkins University in Baltimore.

CHICAGO — Kyphoplasty appears associated with a low rate of complications in patients with osteoporotic or osteolytic vertebral compression fractures, according to the results of a prospective study presented at the annual meeting of the North American Spine Society.

Functional disability also improves over the long run. Such findings emerge just as use of the technique for treating vertebral compression fractures is gaining in popularity and questions about its safety and efficacy are being raised.

According to a review of the literature and complications reported to the Food and Drug Administration, the main safety concerns involve reactions to the use of acrylic (polymethylmethacrylate) bone cement, including hypotension and in some cases death, especially when multiple vertebral levels are treated in one setting. The procedure has also been linked with an increased rate of pedicle fracture and cord compression (J. Vasc. Interv. Radiol. 2004;15:1185-92).

In addition, a retrospective chart review involving 38 consecutive patients indicated that the risk of subsequent fracture in adjacent vertebrae was higher after kyphoplasty than in untreated patients, suggesting that kyphoplasty may shift stress to adjacent vertebrae (Spine 2004;29:2270-6).

In this latest prospective study, a total of 329 consecutive patients with osteoporotic or osteolytic vertebral compression fractures underwent 917 kyphoplasty procedures. Surgeries were performed at the Cleveland Clinic, said Isador Lieberman, M.D., director of its minimally invasive surgery center and center for advanced skills training, and the study's lead investigator.

The rate of subsequent compression fractures in the osteoporotic patients was 11.5%, which is almost half the natural history rate, reported Dr. Lieberman, who is one of the developers of kyphoplasty and is a paid consultant to Kyphon Inc., which manufacturers the inflatable bone tamp.

Study participants were a mean age of 69.2 years and 209 were female. All patients had painful compression fractures secondary to primary osteoporosis (228 patients), multiple myeloma (80 patients), or other malignancy (21 patients) that was refractory to nonoperative treatment.

The levels treated ranged from T3 to L5, with about half of the procedures at the thoracolumbar junction. Local anesthesia was used in 32 procedures. The average length of hospital stay was 1 day, with a range of 0.5 to 9 days.

Complications included cement leaks, which occurred in 24 patients, but none were clinically significant. One patient suffered a perioperative myocardial infarction. There were no neurologic complications or cement reactions, said Dr. Lieberman, who called the issue of such reactions as reported in the literature “misleading and erroneous.”

Short Form-36 (SF-36) health survey data pre- and post operative were available on 237 patients, with a mean of 55 weeks' follow-up.

SF-36 scores improved significantly in every category except general health, which was unchanged. Measures of physical functioning improved on a 0-to-100 scale from 22 to 36, bodily pain from 22 to 42, vitality from 31 to 41, social functioning from 38 to 61, emotional well-being from 55 to 66, and mental health from 63 to 68. “We advocate the use of kyphoplasty [as an] early intervention for osteoporotic and osteolytic vertebral compression fractures to prevent pain and progressive kyphosis,” said study investigator A. Jay Khanna, M.D.

Overall, Oswestry Disability Index scores improved from 48 to 34.3 (−13.7) and such improvements were similar for patients with osteoporosis and myeloma, (−15.8 and −14.5, respectively), said Dr. Khanna, who conducted the study at the Cleveland Clinic but is now at Johns Hopkins University in Baltimore.

CHICAGO — Kyphoplasty appears associated with a low rate of complications in patients with osteoporotic or osteolytic vertebral compression fractures, according to the results of a prospective study presented at the annual meeting of the North American Spine Society.

Functional disability also improves over the long run. Such findings emerge just as use of the technique for treating vertebral compression fractures is gaining in popularity and questions about its safety and efficacy are being raised.

According to a review of the literature and complications reported to the Food and Drug Administration, the main safety concerns involve reactions to the use of acrylic (polymethylmethacrylate) bone cement, including hypotension and in some cases death, especially when multiple vertebral levels are treated in one setting. The procedure has also been linked with an increased rate of pedicle fracture and cord compression (J. Vasc. Interv. Radiol. 2004;15:1185-92).

In addition, a retrospective chart review involving 38 consecutive patients indicated that the risk of subsequent fracture in adjacent vertebrae was higher after kyphoplasty than in untreated patients, suggesting that kyphoplasty may shift stress to adjacent vertebrae (Spine 2004;29:2270-6).

In this latest prospective study, a total of 329 consecutive patients with osteoporotic or osteolytic vertebral compression fractures underwent 917 kyphoplasty procedures. Surgeries were performed at the Cleveland Clinic, said Isador Lieberman, M.D., director of its minimally invasive surgery center and center for advanced skills training, and the study's lead investigator.

The rate of subsequent compression fractures in the osteoporotic patients was 11.5%, which is almost half the natural history rate, reported Dr. Lieberman, who is one of the developers of kyphoplasty and is a paid consultant to Kyphon Inc., which manufacturers the inflatable bone tamp.

Study participants were a mean age of 69.2 years and 209 were female. All patients had painful compression fractures secondary to primary osteoporosis (228 patients), multiple myeloma (80 patients), or other malignancy (21 patients) that was refractory to nonoperative treatment.

The levels treated ranged from T3 to L5, with about half of the procedures at the thoracolumbar junction. Local anesthesia was used in 32 procedures. The average length of hospital stay was 1 day, with a range of 0.5 to 9 days.

Complications included cement leaks, which occurred in 24 patients, but none were clinically significant. One patient suffered a perioperative myocardial infarction. There were no neurologic complications or cement reactions, said Dr. Lieberman, who called the issue of such reactions as reported in the literature “misleading and erroneous.”

Short Form-36 (SF-36) health survey data pre- and post operative were available on 237 patients, with a mean of 55 weeks' follow-up.

SF-36 scores improved significantly in every category except general health, which was unchanged. Measures of physical functioning improved on a 0-to-100 scale from 22 to 36, bodily pain from 22 to 42, vitality from 31 to 41, social functioning from 38 to 61, emotional well-being from 55 to 66, and mental health from 63 to 68. “We advocate the use of kyphoplasty [as an] early intervention for osteoporotic and osteolytic vertebral compression fractures to prevent pain and progressive kyphosis,” said study investigator A. Jay Khanna, M.D.

Overall, Oswestry Disability Index scores improved from 48 to 34.3 (−13.7) and such improvements were similar for patients with osteoporosis and myeloma, (−15.8 and −14.5, respectively), said Dr. Khanna, who conducted the study at the Cleveland Clinic but is now at Johns Hopkins University in Baltimore.

TORONTO — Intracoronary transfer of autologous bone marrow cells led to improved left ventricular function after acute MI in a randomized trial.

After 6 months, there was a highly significant increase in mean left ventricular ejection fractions (LVEFs) in acute MI patients after intracoronary injection of bone marrow cells, according to data from the Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) study. But treatment did not appear to affect left ventricular remodeling.

“The results from the BOOST trial indicate that intracoronary transfer of autologous bone marrow cells is safe, and enhances left ventricular function” after an MI, Kai Wollert, M.D., said at the annual meeting of the Heart Failure Society of America.

Emerging evidence suggests that direct injection of stem cells and progenitor cells derived from bone marrow can improve cardiac function in patients after acute MI. Although only 30 patients were treated with bone marrow cells in the BOOST trial, the results are promising, said Dr. Wollert of Hannover (Germany) Medical School.

“Subgroup analysis must be viewed with caution, considering the size of our study population,” Dr. Wollert said. “However, it was encouraging to see that the effects of bone marrow transfer were observable in all investigated subgroups—men and women, older people, younger people—regardless of the prevalence of risk factors, the time from symptoms to PCI [percutaneous coronary intervention], the infarct localization, and the baseline ejection fraction, or baseline infarct size.”

In the BOOST trial, 60 patients (42 men, 18 women) were evenly randomized after successful PCI to receive optimal medical treatment or optimal medical treatment plus intracoronary transfer of autologous bone-marrow cells 5 days after PCI or 6 days after symptom onset.

There were no significant differences between groups in regard to age, major cardiovascular risk factors, time from symptoms to PCI, infarct size, or treatment with thrombolytics or ACE inhibitors during the primary intervention. More than 90% of patients received aspirin, ACE inhibitors, β-blockers, and statins—both at discharge and at 6 month follow-up.

Investigators harvested 128 mL of bone marrow from the posterior iliac crest, which was reduced to an average volume of 26 mL. The final preparation contained 25 × 10

Dr. Wollert said the study's institutional review board would not allow sham catheterizations, but MRI investigators were blinded to the treatment assignment. The primary end point was change in global LVEF from baseline to 6 months' follow-up, as determined by cardiac MRI.

After 6 months, mean global LVEF had increased by 6.7% in the bone-marrow-cell group vs. 0.7% in the control group, a highly significant difference. LVEFs in the treatment group were 50% at baseline and 56.7% at 6 months vs. 51.3% and 52.0%, respectively, in the control group.

There was no significant difference between groups in regional wall motion from baseline to follow-up. However, transfer of bone marrow cells enhanced left ventricular systolic function primarily in the border zones of the infarct.

The secondary end point of left ventricular end-diastolic volume index (LVEDVI) increased for both groups during the 6-month follow-up. But the difference in LVEDVI change was not significantly different between the two groups, suggesting that bone marrow cell transfer does not affect left ventricular remodeling after MI, Dr. Wollert said.

Cell transfer did not increase the risk of adverse events, in-stent restenosis, or proarrhythmic effects. There was no significant difference in extrasystole between groups, although there was a trend toward fewer ventricular extrasystole in the bone marrow cell transfer group.

Dr. Wollert said that future studies should utilize a double-blind design with sham catheterizations, and ultimately address the impact of bone marrow transfer on clinical end points in a large patient population.

TORONTO — Intracoronary transfer of autologous bone marrow cells led to improved left ventricular function after acute MI in a randomized trial.

After 6 months, there was a highly significant increase in mean left ventricular ejection fractions (LVEFs) in acute MI patients after intracoronary injection of bone marrow cells, according to data from the Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) study. But treatment did not appear to affect left ventricular remodeling.

“The results from the BOOST trial indicate that intracoronary transfer of autologous bone marrow cells is safe, and enhances left ventricular function” after an MI, Kai Wollert, M.D., said at the annual meeting of the Heart Failure Society of America.

Emerging evidence suggests that direct injection of stem cells and progenitor cells derived from bone marrow can improve cardiac function in patients after acute MI. Although only 30 patients were treated with bone marrow cells in the BOOST trial, the results are promising, said Dr. Wollert of Hannover (Germany) Medical School.

“Subgroup analysis must be viewed with caution, considering the size of our study population,” Dr. Wollert said. “However, it was encouraging to see that the effects of bone marrow transfer were observable in all investigated subgroups—men and women, older people, younger people—regardless of the prevalence of risk factors, the time from symptoms to PCI [percutaneous coronary intervention], the infarct localization, and the baseline ejection fraction, or baseline infarct size.”

In the BOOST trial, 60 patients (42 men, 18 women) were evenly randomized after successful PCI to receive optimal medical treatment or optimal medical treatment plus intracoronary transfer of autologous bone-marrow cells 5 days after PCI or 6 days after symptom onset.

There were no significant differences between groups in regard to age, major cardiovascular risk factors, time from symptoms to PCI, infarct size, or treatment with thrombolytics or ACE inhibitors during the primary intervention. More than 90% of patients received aspirin, ACE inhibitors, β-blockers, and statins—both at discharge and at 6 month follow-up.

Investigators harvested 128 mL of bone marrow from the posterior iliac crest, which was reduced to an average volume of 26 mL. The final preparation contained 25 × 10

Dr. Wollert said the study's institutional review board would not allow sham catheterizations, but MRI investigators were blinded to the treatment assignment. The primary end point was change in global LVEF from baseline to 6 months' follow-up, as determined by cardiac MRI.

After 6 months, mean global LVEF had increased by 6.7% in the bone-marrow-cell group vs. 0.7% in the control group, a highly significant difference. LVEFs in the treatment group were 50% at baseline and 56.7% at 6 months vs. 51.3% and 52.0%, respectively, in the control group.

There was no significant difference between groups in regional wall motion from baseline to follow-up. However, transfer of bone marrow cells enhanced left ventricular systolic function primarily in the border zones of the infarct.

The secondary end point of left ventricular end-diastolic volume index (LVEDVI) increased for both groups during the 6-month follow-up. But the difference in LVEDVI change was not significantly different between the two groups, suggesting that bone marrow cell transfer does not affect left ventricular remodeling after MI, Dr. Wollert said.

Cell transfer did not increase the risk of adverse events, in-stent restenosis, or proarrhythmic effects. There was no significant difference in extrasystole between groups, although there was a trend toward fewer ventricular extrasystole in the bone marrow cell transfer group.

Dr. Wollert said that future studies should utilize a double-blind design with sham catheterizations, and ultimately address the impact of bone marrow transfer on clinical end points in a large patient population.

TORONTO — Intracoronary transfer of autologous bone marrow cells led to improved left ventricular function after acute MI in a randomized trial.

After 6 months, there was a highly significant increase in mean left ventricular ejection fractions (LVEFs) in acute MI patients after intracoronary injection of bone marrow cells, according to data from the Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) study. But treatment did not appear to affect left ventricular remodeling.

“The results from the BOOST trial indicate that intracoronary transfer of autologous bone marrow cells is safe, and enhances left ventricular function” after an MI, Kai Wollert, M.D., said at the annual meeting of the Heart Failure Society of America.

Emerging evidence suggests that direct injection of stem cells and progenitor cells derived from bone marrow can improve cardiac function in patients after acute MI. Although only 30 patients were treated with bone marrow cells in the BOOST trial, the results are promising, said Dr. Wollert of Hannover (Germany) Medical School.

“Subgroup analysis must be viewed with caution, considering the size of our study population,” Dr. Wollert said. “However, it was encouraging to see that the effects of bone marrow transfer were observable in all investigated subgroups—men and women, older people, younger people—regardless of the prevalence of risk factors, the time from symptoms to PCI [percutaneous coronary intervention], the infarct localization, and the baseline ejection fraction, or baseline infarct size.”

In the BOOST trial, 60 patients (42 men, 18 women) were evenly randomized after successful PCI to receive optimal medical treatment or optimal medical treatment plus intracoronary transfer of autologous bone-marrow cells 5 days after PCI or 6 days after symptom onset.

There were no significant differences between groups in regard to age, major cardiovascular risk factors, time from symptoms to PCI, infarct size, or treatment with thrombolytics or ACE inhibitors during the primary intervention. More than 90% of patients received aspirin, ACE inhibitors, β-blockers, and statins—both at discharge and at 6 month follow-up.

Investigators harvested 128 mL of bone marrow from the posterior iliac crest, which was reduced to an average volume of 26 mL. The final preparation contained 25 × 10

Dr. Wollert said the study's institutional review board would not allow sham catheterizations, but MRI investigators were blinded to the treatment assignment. The primary end point was change in global LVEF from baseline to 6 months' follow-up, as determined by cardiac MRI.

After 6 months, mean global LVEF had increased by 6.7% in the bone-marrow-cell group vs. 0.7% in the control group, a highly significant difference. LVEFs in the treatment group were 50% at baseline and 56.7% at 6 months vs. 51.3% and 52.0%, respectively, in the control group.

There was no significant difference between groups in regional wall motion from baseline to follow-up. However, transfer of bone marrow cells enhanced left ventricular systolic function primarily in the border zones of the infarct.

The secondary end point of left ventricular end-diastolic volume index (LVEDVI) increased for both groups during the 6-month follow-up. But the difference in LVEDVI change was not significantly different between the two groups, suggesting that bone marrow cell transfer does not affect left ventricular remodeling after MI, Dr. Wollert said.

Cell transfer did not increase the risk of adverse events, in-stent restenosis, or proarrhythmic effects. There was no significant difference in extrasystole between groups, although there was a trend toward fewer ventricular extrasystole in the bone marrow cell transfer group.

Dr. Wollert said that future studies should utilize a double-blind design with sham catheterizations, and ultimately address the impact of bone marrow transfer on clinical end points in a large patient population.