Timothy F. Kirn

SAN ANTONIO — Women who are taking raloxifene for osteoporosis do not need to stop taking the bisphosphonate to begin parathyroid hormone therapy.

In fact, the two drugs may have some synergy, Chad Deal, M.D., said at the annual meeting of the American College of Rheumatology.

In a 6-month study comparing parathyroid hormone (1–34) plus raloxifene with parathyroid hormone monotherapy, the combination increased total hip bone density to a greater degree, observed Dr. Deal, head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic Foundation.

The combination “could potentially enlarge the anabolic window, maximizing the formation of bone and minimizing the resorption of bone,” said Dr. Deal, whose study included measurements of bone turnover markers.

Dr. Deal's double-blind study enrolled 137 subjects who were randomized to daily therapy with either the combination of teriparatide (Forteo), 20 mcg, plus raloxifene (Evista), 60 mg, or to monotherapy with teriparatide, 20 mcg.

All of the study participants also received calcium and vitamin D supplementation.

At 6 months' follow-up, the combination of raloxifene and parathyroid hormone increased bone mineral density over baseline by a mean 6.19% at the lumbar spine, a mean 2.23% at the femoral neck, and a mean 2.31% for the total hip, as measured by dual x-ray absorptiometry.

By comparison, teriparatide increased lumbar spine density by a mean 5.19%, femoral neck density by a mean 1.03%, and total hip density by 0.68%.

The differences at the lumbar spine and the femoral neck were not statistically significant, but the difference at the total hip was, Dr. Deal said.

Investigators have been intrigued by the possibility of combination treatment for osteoporosis for some time, he said.

But the only other previous major study of combination treatment looked at the use of parathyroid hormone with alendronate; it suggested that the addition of alendronate appeared to inhibit the ability of parathyroid hormone to stimulate new bone formation.

The two studies differ in several ways that make them difficult to compare.

In the alendronate trial, the addition of alendronate decreased the level of serum procollagen type I N-terminal propeptide (PINP)—a marker of bone formation—by 15% from baseline at 6 months.

In the raloxifene trial, PINP in the combination group was increased from baseline to a mean level similar to that seen among patients receiving teriparatide alone.

Moreover, bone resorption was suppressed by both the teriparatide alone and the raloxifene-teriparatide combination, as measured by serum type I collagen C-telopeptide level.

“The limitation of this trial, of course, is that it is too small to assess the important outcome, which is fracture,” Dr. Deal said.

The combination was well tolerated.

Subjects in both groups had similar increases in serum uric acid levels, but there were no cases of gout, he added.

The clinical trial was sponsored by Eli Lilly & Co., which makes both Evista and Forteo.

SAN ANTONIO — Women who are taking raloxifene for osteoporosis do not need to stop taking the bisphosphonate to begin parathyroid hormone therapy.

In fact, the two drugs may have some synergy, Chad Deal, M.D., said at the annual meeting of the American College of Rheumatology.

In a 6-month study comparing parathyroid hormone (1–34) plus raloxifene with parathyroid hormone monotherapy, the combination increased total hip bone density to a greater degree, observed Dr. Deal, head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic Foundation.

The combination “could potentially enlarge the anabolic window, maximizing the formation of bone and minimizing the resorption of bone,” said Dr. Deal, whose study included measurements of bone turnover markers.

Dr. Deal's double-blind study enrolled 137 subjects who were randomized to daily therapy with either the combination of teriparatide (Forteo), 20 mcg, plus raloxifene (Evista), 60 mg, or to monotherapy with teriparatide, 20 mcg.

All of the study participants also received calcium and vitamin D supplementation.

At 6 months' follow-up, the combination of raloxifene and parathyroid hormone increased bone mineral density over baseline by a mean 6.19% at the lumbar spine, a mean 2.23% at the femoral neck, and a mean 2.31% for the total hip, as measured by dual x-ray absorptiometry.

By comparison, teriparatide increased lumbar spine density by a mean 5.19%, femoral neck density by a mean 1.03%, and total hip density by 0.68%.

The differences at the lumbar spine and the femoral neck were not statistically significant, but the difference at the total hip was, Dr. Deal said.

Investigators have been intrigued by the possibility of combination treatment for osteoporosis for some time, he said.

But the only other previous major study of combination treatment looked at the use of parathyroid hormone with alendronate; it suggested that the addition of alendronate appeared to inhibit the ability of parathyroid hormone to stimulate new bone formation.

The two studies differ in several ways that make them difficult to compare.

In the alendronate trial, the addition of alendronate decreased the level of serum procollagen type I N-terminal propeptide (PINP)—a marker of bone formation—by 15% from baseline at 6 months.

In the raloxifene trial, PINP in the combination group was increased from baseline to a mean level similar to that seen among patients receiving teriparatide alone.

Moreover, bone resorption was suppressed by both the teriparatide alone and the raloxifene-teriparatide combination, as measured by serum type I collagen C-telopeptide level.

“The limitation of this trial, of course, is that it is too small to assess the important outcome, which is fracture,” Dr. Deal said.

The combination was well tolerated.

Subjects in both groups had similar increases in serum uric acid levels, but there were no cases of gout, he added.

The clinical trial was sponsored by Eli Lilly & Co., which makes both Evista and Forteo.

SAN ANTONIO — Women who are taking raloxifene for osteoporosis do not need to stop taking the bisphosphonate to begin parathyroid hormone therapy.

In fact, the two drugs may have some synergy, Chad Deal, M.D., said at the annual meeting of the American College of Rheumatology.

In a 6-month study comparing parathyroid hormone (1–34) plus raloxifene with parathyroid hormone monotherapy, the combination increased total hip bone density to a greater degree, observed Dr. Deal, head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic Foundation.

The combination “could potentially enlarge the anabolic window, maximizing the formation of bone and minimizing the resorption of bone,” said Dr. Deal, whose study included measurements of bone turnover markers.

Dr. Deal's double-blind study enrolled 137 subjects who were randomized to daily therapy with either the combination of teriparatide (Forteo), 20 mcg, plus raloxifene (Evista), 60 mg, or to monotherapy with teriparatide, 20 mcg.

All of the study participants also received calcium and vitamin D supplementation.

At 6 months' follow-up, the combination of raloxifene and parathyroid hormone increased bone mineral density over baseline by a mean 6.19% at the lumbar spine, a mean 2.23% at the femoral neck, and a mean 2.31% for the total hip, as measured by dual x-ray absorptiometry.

By comparison, teriparatide increased lumbar spine density by a mean 5.19%, femoral neck density by a mean 1.03%, and total hip density by 0.68%.

The differences at the lumbar spine and the femoral neck were not statistically significant, but the difference at the total hip was, Dr. Deal said.

Investigators have been intrigued by the possibility of combination treatment for osteoporosis for some time, he said.

But the only other previous major study of combination treatment looked at the use of parathyroid hormone with alendronate; it suggested that the addition of alendronate appeared to inhibit the ability of parathyroid hormone to stimulate new bone formation.

The two studies differ in several ways that make them difficult to compare.

In the alendronate trial, the addition of alendronate decreased the level of serum procollagen type I N-terminal propeptide (PINP)—a marker of bone formation—by 15% from baseline at 6 months.

In the raloxifene trial, PINP in the combination group was increased from baseline to a mean level similar to that seen among patients receiving teriparatide alone.

Moreover, bone resorption was suppressed by both the teriparatide alone and the raloxifene-teriparatide combination, as measured by serum type I collagen C-telopeptide level.

“The limitation of this trial, of course, is that it is too small to assess the important outcome, which is fracture,” Dr. Deal said.

The combination was well tolerated.

Subjects in both groups had similar increases in serum uric acid levels, but there were no cases of gout, he added.

The clinical trial was sponsored by Eli Lilly & Co., which makes both Evista and Forteo.

VICTORIA, B.C. — An open-label trial of Canadian patients seen in regular clinics and offices has confirmed that desloratadine treatment of chronic idiopathic urticaria is highly effective, Charles W. Lynde, M.D., said at the annual meeting of the Canadian Dermatology Association.

This is a result that previously had been shown only in highly regulated, and perhaps artificial, clinic trials, he said.

In this study, 348 patients received 5 mg of the drug once daily for 2 weeks.

A total of 45% of the patients had complete or marked improvement, 19% had moderate improvement, 22% had mild improvement, and 14% had no improvement.

“We found this very effective for the relief of chronic urticaria,” said Dr. Lynde of the University of Toronto.

Improvement was rated by both the treating physicians (on days 7 and 14 of treatment) and by the patients on a daily basis.

There was a high concurrence between physician and patient ratings.

At day 14 of treatment, mean scores rating pruritus fell by 55%, mean scores on hive numbers fell by 52%, and mean scores rating the overall condition fell 48%.

Desloratadine, which is a nonsedating, selective antihistamine, can often produce improvement with the very first dose, Dr. Lynde added.

The study also looked at quality of life measures and found mean improvements of 30%–50% in all the specific areas examined. Some of these measures were sleep, self-consciousness, and even sexual activity.

Dr. Lynde said that in the past he has received financial support from Schering-Plough Corp., the company that manufactures desloratadine (Clarinex).

VICTORIA, B.C. — An open-label trial of Canadian patients seen in regular clinics and offices has confirmed that desloratadine treatment of chronic idiopathic urticaria is highly effective, Charles W. Lynde, M.D., said at the annual meeting of the Canadian Dermatology Association.

This is a result that previously had been shown only in highly regulated, and perhaps artificial, clinic trials, he said.

In this study, 348 patients received 5 mg of the drug once daily for 2 weeks.

A total of 45% of the patients had complete or marked improvement, 19% had moderate improvement, 22% had mild improvement, and 14% had no improvement.

“We found this very effective for the relief of chronic urticaria,” said Dr. Lynde of the University of Toronto.

Improvement was rated by both the treating physicians (on days 7 and 14 of treatment) and by the patients on a daily basis.

There was a high concurrence between physician and patient ratings.

At day 14 of treatment, mean scores rating pruritus fell by 55%, mean scores on hive numbers fell by 52%, and mean scores rating the overall condition fell 48%.

Desloratadine, which is a nonsedating, selective antihistamine, can often produce improvement with the very first dose, Dr. Lynde added.

The study also looked at quality of life measures and found mean improvements of 30%–50% in all the specific areas examined. Some of these measures were sleep, self-consciousness, and even sexual activity.

Dr. Lynde said that in the past he has received financial support from Schering-Plough Corp., the company that manufactures desloratadine (Clarinex).

VICTORIA, B.C. — An open-label trial of Canadian patients seen in regular clinics and offices has confirmed that desloratadine treatment of chronic idiopathic urticaria is highly effective, Charles W. Lynde, M.D., said at the annual meeting of the Canadian Dermatology Association.

This is a result that previously had been shown only in highly regulated, and perhaps artificial, clinic trials, he said.

In this study, 348 patients received 5 mg of the drug once daily for 2 weeks.

A total of 45% of the patients had complete or marked improvement, 19% had moderate improvement, 22% had mild improvement, and 14% had no improvement.

“We found this very effective for the relief of chronic urticaria,” said Dr. Lynde of the University of Toronto.

Improvement was rated by both the treating physicians (on days 7 and 14 of treatment) and by the patients on a daily basis.

There was a high concurrence between physician and patient ratings.

At day 14 of treatment, mean scores rating pruritus fell by 55%, mean scores on hive numbers fell by 52%, and mean scores rating the overall condition fell 48%.

Desloratadine, which is a nonsedating, selective antihistamine, can often produce improvement with the very first dose, Dr. Lynde added.

The study also looked at quality of life measures and found mean improvements of 30%–50% in all the specific areas examined. Some of these measures were sleep, self-consciousness, and even sexual activity.

Dr. Lynde said that in the past he has received financial support from Schering-Plough Corp., the company that manufactures desloratadine (Clarinex).

In places like Maryland, Pennsylvania, and Florida, some physicians are reportedly giving up providing high-risk services, retiring, or packing their bags for somewhere else because of the current professional liability crisis.

Colorado, on the other hand, has no such problem. In fact, medical malpractice insurance rates in Colorado may be attracting physicians.

Why? Many say it is because Colorado has a cap of $1 million on malpractice awards, including $300,000 allowed for noneconomic damages such as disfigurement and physical disability.

The cap reportedly has kept rates and increases down. At a three-physician, family medicine clinic in Leadville, the three physicians pay about $16,000 each for malpractice coverage, and including coverage for obstetric care. Last year, their rates rose 4%, and this year, their rates will increase 6.7%, said Shelly Miller, office administrator at the Leadville Medical Center.

In some other states in recent years, annual rate increases have been said to be as high as 20%–30%.

In 1988, the year Colorado enacted limits on malpractice awards, the average obstetrician, for example, paid $61,904 in malpractice insurance premiums, according to George Dikeou, a legislative consultant in Denver for COPIC, the nonprofit, physician-run insurer that covers malpractice for about 80% of all physicians in Colorado. Adjusted for inflation, that would equal more than $100,000 today. But last year, the average Colorado obstetrician paid $37,206 for COPIC coverage, Mr. Dikeou said.

The cap is not a hard limit—juries can award more than a million, but then the award must be reviewed by the judge—but it has limited awards and that has contributed to the low premiums. The largest verdict ever in Colorado was for $3.2 million, Mr. Dikeou said.

Some evidence suggests that the low rates may be attracting physicians to Colorado, or at least keeping them there.

“Living and practicing medicine is more affordable here, and malpractice rates are part of that,” said Kern Low, M.D., a family physician in Pueblo. According to figures from Peregrine Management Corp., a practice consulting firm in Lakewood, 2,178 physicians relocated to Colorado last year. Of those, 50% came from the 19 states that the American Medical Association has identified as “crisis” states, where escalating premiums are threatening practices and perhaps compromising the availability of physicians. Another 40% of those physicians came from states that aren't crisis states but have been hard hit by recent premium increases.

The Colorado Medical Society and others said they have not seen a flood tide of new physicians flocking to its borders, but neither are doctors abandoning practice or fleeing.

“We've got a part of the puzzle but we aren't the golden goose,” said Dean Holzkamp, a spokesperson for the medical society, who noted that in Colorado reimbursement is considered very low. “I haven't heard of any mass influx of doctors. But we aren't seeing an exodus either. We don't have any shortage of being able to deliver babies.

“We're growing, but our state is growing,” he said.

Colorado is unique in that one nonprofit company insures such a large number of physicians, but a recent study showed that caps do make a difference. Conducted by Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, the study found that average premiums are 17% lower in states with caps than in states without caps.

Another recent study, from the federal Agency for Healthcare Research and Quality, found that states with limits on malpractice awards have about 12% more doctors per capita than states without limits.

“Caps are a good thing,” Dr. Thorpe told this newspaper.

Plaintiffs' lawyers in Colorado do complain that the cap makes it economically unfeasible for some individuals to bring legitimate suits, said Dayna Bowen Matthew, a malpractice expert at the University of Colorado at Boulder. But there is no hard evidence that this is the case.

On the other hand, what has been shown in many places is that caps do discourage frivolous lawsuits, and that saves insurance companies money. “We have done a good job here in terms of keeping doctors and limiting frivolous lawsuits,” Ms. Bowen Matthew said. “It is something that other states should be aware of.”

She recently relocated to Colorado with her husband, a cardiovascular surgeon; malpractice rates were one of the things that factored into the decision to choose Colorado.

Rates in Colorado have not been stagnant during the recent run-up elsewhere, as critics of the state cap—such as Sen. Diana DeGette (D-Colo.)—are quick to point out. In the last 3 years, rates have increased 13%–15% each year.

But supporters of the cap attribute those increases to two state Supreme Court decisions, rendered in 2001 and 2002, that appeared to undermine the cap. One decision said that in cases where there was disfigurement, the limit on noneconomic damages did not apply. The other held that corporations that employed a physician could also be sued.

After those rulings, COPIC saw an increase in the number of cases it had to defend that alleged disfigurement, Mr. Dikeou said. In 2003, the cases forced the legislature to sit down with cap supporters, and they forged a compromise that amended the law to overturn those decisions. The compromise was that the cap on noneconomic damages was raised from $250,000 to the present $300,000.

The compromise means that Colorado's double-digit increases should be over, said Alethia Morgan, M.D., president of the Colorado Medical Society and a member of the board of directors of COPIC.

“I expect that next year we will see single-digit increases again,” she said.

The cap on awards is just part of what Colorado is doing to keep rates down, said Douglas H. Kirkpatrick, M.D., vice president of the American College of Obstetricians and Gynecologists.

Dr. Kirkpatrick, who practices in Denver, noted that in 2003 the Colorado legislature passed an “I am sorry” law. The law allows physicians to work with a patient who has had a bad outcome, and even take responsibility for the situation, but prevents anything they say during that process from being allowed into court.

COPIC is being proactive as well. The company recently completed a 3-year, pilot program designed to encourage physicians to deal with patients who have had an adverse outcome before they file a suit.

The physicians who signed up for the program agreed to report to the company any adverse outcome within 24 hours of its occurrence. When a report was made, the company stepped in to work with the doctor and the patient, with an emphasis on listening to the patient, and even admitting mistakes where they were made.

The goal was to preempt the patients' concerns and anger from turning into the kind of antagonism that prompts a malpractice suit. The program even disbursed money to patients when it was needed for further medical care or because of missed work, with a limit of $30,000.

The pilot program was so successful that it is now being adopted company wide, Mr. Dikeou said. During the 18 months the pilot program was fully in place, 592 encounters were reported. Of those, 360 cases involved discussions with the patient and nothing more. In 232 cases, some disbursement of money was made, but in every case it was much less than would have been spent even fighting a suit that was dismissed, he said.

So far, no suits have been filed.

“We're doing stuff here in Colorado that nobody else is doing right now,” Mr. Dikeou said.

In places like Maryland, Pennsylvania, and Florida, some physicians are reportedly giving up providing high-risk services, retiring, or packing their bags for somewhere else because of the current professional liability crisis.

Colorado, on the other hand, has no such problem. In fact, medical malpractice insurance rates in Colorado may be attracting physicians.

Why? Many say it is because Colorado has a cap of $1 million on malpractice awards, including $300,000 allowed for noneconomic damages such as disfigurement and physical disability.

The cap reportedly has kept rates and increases down. At a three-physician, family medicine clinic in Leadville, the three physicians pay about $16,000 each for malpractice coverage, and including coverage for obstetric care. Last year, their rates rose 4%, and this year, their rates will increase 6.7%, said Shelly Miller, office administrator at the Leadville Medical Center.

In some other states in recent years, annual rate increases have been said to be as high as 20%–30%.

In 1988, the year Colorado enacted limits on malpractice awards, the average obstetrician, for example, paid $61,904 in malpractice insurance premiums, according to George Dikeou, a legislative consultant in Denver for COPIC, the nonprofit, physician-run insurer that covers malpractice for about 80% of all physicians in Colorado. Adjusted for inflation, that would equal more than $100,000 today. But last year, the average Colorado obstetrician paid $37,206 for COPIC coverage, Mr. Dikeou said.

The cap is not a hard limit—juries can award more than a million, but then the award must be reviewed by the judge—but it has limited awards and that has contributed to the low premiums. The largest verdict ever in Colorado was for $3.2 million, Mr. Dikeou said.

Some evidence suggests that the low rates may be attracting physicians to Colorado, or at least keeping them there.

“Living and practicing medicine is more affordable here, and malpractice rates are part of that,” said Kern Low, M.D., a family physician in Pueblo. According to figures from Peregrine Management Corp., a practice consulting firm in Lakewood, 2,178 physicians relocated to Colorado last year. Of those, 50% came from the 19 states that the American Medical Association has identified as “crisis” states, where escalating premiums are threatening practices and perhaps compromising the availability of physicians. Another 40% of those physicians came from states that aren't crisis states but have been hard hit by recent premium increases.

The Colorado Medical Society and others said they have not seen a flood tide of new physicians flocking to its borders, but neither are doctors abandoning practice or fleeing.

“We've got a part of the puzzle but we aren't the golden goose,” said Dean Holzkamp, a spokesperson for the medical society, who noted that in Colorado reimbursement is considered very low. “I haven't heard of any mass influx of doctors. But we aren't seeing an exodus either. We don't have any shortage of being able to deliver babies.

“We're growing, but our state is growing,” he said.

Colorado is unique in that one nonprofit company insures such a large number of physicians, but a recent study showed that caps do make a difference. Conducted by Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, the study found that average premiums are 17% lower in states with caps than in states without caps.

Another recent study, from the federal Agency for Healthcare Research and Quality, found that states with limits on malpractice awards have about 12% more doctors per capita than states without limits.

“Caps are a good thing,” Dr. Thorpe told this newspaper.

Plaintiffs' lawyers in Colorado do complain that the cap makes it economically unfeasible for some individuals to bring legitimate suits, said Dayna Bowen Matthew, a malpractice expert at the University of Colorado at Boulder. But there is no hard evidence that this is the case.

On the other hand, what has been shown in many places is that caps do discourage frivolous lawsuits, and that saves insurance companies money. “We have done a good job here in terms of keeping doctors and limiting frivolous lawsuits,” Ms. Bowen Matthew said. “It is something that other states should be aware of.”

She recently relocated to Colorado with her husband, a cardiovascular surgeon; malpractice rates were one of the things that factored into the decision to choose Colorado.

Rates in Colorado have not been stagnant during the recent run-up elsewhere, as critics of the state cap—such as Sen. Diana DeGette (D-Colo.)—are quick to point out. In the last 3 years, rates have increased 13%–15% each year.

But supporters of the cap attribute those increases to two state Supreme Court decisions, rendered in 2001 and 2002, that appeared to undermine the cap. One decision said that in cases where there was disfigurement, the limit on noneconomic damages did not apply. The other held that corporations that employed a physician could also be sued.

After those rulings, COPIC saw an increase in the number of cases it had to defend that alleged disfigurement, Mr. Dikeou said. In 2003, the cases forced the legislature to sit down with cap supporters, and they forged a compromise that amended the law to overturn those decisions. The compromise was that the cap on noneconomic damages was raised from $250,000 to the present $300,000.

The compromise means that Colorado's double-digit increases should be over, said Alethia Morgan, M.D., president of the Colorado Medical Society and a member of the board of directors of COPIC.

“I expect that next year we will see single-digit increases again,” she said.

The cap on awards is just part of what Colorado is doing to keep rates down, said Douglas H. Kirkpatrick, M.D., vice president of the American College of Obstetricians and Gynecologists.

Dr. Kirkpatrick, who practices in Denver, noted that in 2003 the Colorado legislature passed an “I am sorry” law. The law allows physicians to work with a patient who has had a bad outcome, and even take responsibility for the situation, but prevents anything they say during that process from being allowed into court.

COPIC is being proactive as well. The company recently completed a 3-year, pilot program designed to encourage physicians to deal with patients who have had an adverse outcome before they file a suit.

The physicians who signed up for the program agreed to report to the company any adverse outcome within 24 hours of its occurrence. When a report was made, the company stepped in to work with the doctor and the patient, with an emphasis on listening to the patient, and even admitting mistakes where they were made.

The goal was to preempt the patients' concerns and anger from turning into the kind of antagonism that prompts a malpractice suit. The program even disbursed money to patients when it was needed for further medical care or because of missed work, with a limit of $30,000.

The pilot program was so successful that it is now being adopted company wide, Mr. Dikeou said. During the 18 months the pilot program was fully in place, 592 encounters were reported. Of those, 360 cases involved discussions with the patient and nothing more. In 232 cases, some disbursement of money was made, but in every case it was much less than would have been spent even fighting a suit that was dismissed, he said.

So far, no suits have been filed.

“We're doing stuff here in Colorado that nobody else is doing right now,” Mr. Dikeou said.

In places like Maryland, Pennsylvania, and Florida, some physicians are reportedly giving up providing high-risk services, retiring, or packing their bags for somewhere else because of the current professional liability crisis.

Colorado, on the other hand, has no such problem. In fact, medical malpractice insurance rates in Colorado may be attracting physicians.

Why? Many say it is because Colorado has a cap of $1 million on malpractice awards, including $300,000 allowed for noneconomic damages such as disfigurement and physical disability.

The cap reportedly has kept rates and increases down. At a three-physician, family medicine clinic in Leadville, the three physicians pay about $16,000 each for malpractice coverage, and including coverage for obstetric care. Last year, their rates rose 4%, and this year, their rates will increase 6.7%, said Shelly Miller, office administrator at the Leadville Medical Center.

In some other states in recent years, annual rate increases have been said to be as high as 20%–30%.

In 1988, the year Colorado enacted limits on malpractice awards, the average obstetrician, for example, paid $61,904 in malpractice insurance premiums, according to George Dikeou, a legislative consultant in Denver for COPIC, the nonprofit, physician-run insurer that covers malpractice for about 80% of all physicians in Colorado. Adjusted for inflation, that would equal more than $100,000 today. But last year, the average Colorado obstetrician paid $37,206 for COPIC coverage, Mr. Dikeou said.

The cap is not a hard limit—juries can award more than a million, but then the award must be reviewed by the judge—but it has limited awards and that has contributed to the low premiums. The largest verdict ever in Colorado was for $3.2 million, Mr. Dikeou said.

Some evidence suggests that the low rates may be attracting physicians to Colorado, or at least keeping them there.

“Living and practicing medicine is more affordable here, and malpractice rates are part of that,” said Kern Low, M.D., a family physician in Pueblo. According to figures from Peregrine Management Corp., a practice consulting firm in Lakewood, 2,178 physicians relocated to Colorado last year. Of those, 50% came from the 19 states that the American Medical Association has identified as “crisis” states, where escalating premiums are threatening practices and perhaps compromising the availability of physicians. Another 40% of those physicians came from states that aren't crisis states but have been hard hit by recent premium increases.

The Colorado Medical Society and others said they have not seen a flood tide of new physicians flocking to its borders, but neither are doctors abandoning practice or fleeing.

“We've got a part of the puzzle but we aren't the golden goose,” said Dean Holzkamp, a spokesperson for the medical society, who noted that in Colorado reimbursement is considered very low. “I haven't heard of any mass influx of doctors. But we aren't seeing an exodus either. We don't have any shortage of being able to deliver babies.

“We're growing, but our state is growing,” he said.

Colorado is unique in that one nonprofit company insures such a large number of physicians, but a recent study showed that caps do make a difference. Conducted by Kenneth E. Thorpe, Ph.D., of Emory University, Atlanta, the study found that average premiums are 17% lower in states with caps than in states without caps.

Another recent study, from the federal Agency for Healthcare Research and Quality, found that states with limits on malpractice awards have about 12% more doctors per capita than states without limits.

“Caps are a good thing,” Dr. Thorpe told this newspaper.

Plaintiffs' lawyers in Colorado do complain that the cap makes it economically unfeasible for some individuals to bring legitimate suits, said Dayna Bowen Matthew, a malpractice expert at the University of Colorado at Boulder. But there is no hard evidence that this is the case.

On the other hand, what has been shown in many places is that caps do discourage frivolous lawsuits, and that saves insurance companies money. “We have done a good job here in terms of keeping doctors and limiting frivolous lawsuits,” Ms. Bowen Matthew said. “It is something that other states should be aware of.”

She recently relocated to Colorado with her husband, a cardiovascular surgeon; malpractice rates were one of the things that factored into the decision to choose Colorado.

Rates in Colorado have not been stagnant during the recent run-up elsewhere, as critics of the state cap—such as Sen. Diana DeGette (D-Colo.)—are quick to point out. In the last 3 years, rates have increased 13%–15% each year.

But supporters of the cap attribute those increases to two state Supreme Court decisions, rendered in 2001 and 2002, that appeared to undermine the cap. One decision said that in cases where there was disfigurement, the limit on noneconomic damages did not apply. The other held that corporations that employed a physician could also be sued.

After those rulings, COPIC saw an increase in the number of cases it had to defend that alleged disfigurement, Mr. Dikeou said. In 2003, the cases forced the legislature to sit down with cap supporters, and they forged a compromise that amended the law to overturn those decisions. The compromise was that the cap on noneconomic damages was raised from $250,000 to the present $300,000.

The compromise means that Colorado's double-digit increases should be over, said Alethia Morgan, M.D., president of the Colorado Medical Society and a member of the board of directors of COPIC.

“I expect that next year we will see single-digit increases again,” she said.

The cap on awards is just part of what Colorado is doing to keep rates down, said Douglas H. Kirkpatrick, M.D., vice president of the American College of Obstetricians and Gynecologists.

Dr. Kirkpatrick, who practices in Denver, noted that in 2003 the Colorado legislature passed an “I am sorry” law. The law allows physicians to work with a patient who has had a bad outcome, and even take responsibility for the situation, but prevents anything they say during that process from being allowed into court.

COPIC is being proactive as well. The company recently completed a 3-year, pilot program designed to encourage physicians to deal with patients who have had an adverse outcome before they file a suit.

The physicians who signed up for the program agreed to report to the company any adverse outcome within 24 hours of its occurrence. When a report was made, the company stepped in to work with the doctor and the patient, with an emphasis on listening to the patient, and even admitting mistakes where they were made.

The goal was to preempt the patients' concerns and anger from turning into the kind of antagonism that prompts a malpractice suit. The program even disbursed money to patients when it was needed for further medical care or because of missed work, with a limit of $30,000.

The pilot program was so successful that it is now being adopted company wide, Mr. Dikeou said. During the 18 months the pilot program was fully in place, 592 encounters were reported. Of those, 360 cases involved discussions with the patient and nothing more. In 232 cases, some disbursement of money was made, but in every case it was much less than would have been spent even fighting a suit that was dismissed, he said.

So far, no suits have been filed.

“We're doing stuff here in Colorado that nobody else is doing right now,” Mr. Dikeou said.

SAN ANTONIO — Treating Helicobacter pylori infection in patients who take NSAIDs does not help prevent the development of peptic ulcer disease, Willem F. Lems, M.D., said at the annual meeting of the American College of Rheumatology.

In his study, 347 patients with culture-confirmed, H. pylori infection and a history of long-term NSAID use were randomized to receive H. pylori eradication treatment or a placebo.

Three months after treatment, peptic ulcers were diagnosed by endoscopy in 6 of 172 patients who had been actively treated, compared with 8 of 175 patients in the placebo group. One patient in the treated group and two patients in the placebo group developed endoscopic duodenal ulcers.

There was no significant difference between the groups in terms of the prevalence of gastroduodenal erosions (41 treated versus 51 placebo). Nor was there any difference in the rate of dyspepsia.

No patient in either group developed a symptomatic ulcer, an ulcer bleed, or ulcer perforation at any time during a full 12-month follow-up.

At the 3-month endoscopic examination, 87% of the treated patients and 21% of the placebo-treated patients were free of H. pylori.

The study adds to a body of literature on H. pylori and NSAID-associated ulcer that has been a bit confusing, said Dr. Lems of VU University Medical Center, Amsterdam.

While H. pylori eradication has been shown definitively to reduce ulcer recurrence in patients not taking NSAIDs, reports on what eradication does for patients on NSAIDs have been conflicting.

Although his study has the scientific strength of being a prospective trial, Dr. Lems said, it also could have been confounded by the fact that patients had to have been on long-term NSAID therapy already. His patients could have been a select group who were already able to tolerate NSAID treatment, and the results of treatment could be different for individuals just starting treatment.

A fairly large percentage of the patients (53%) were either on gastroprotective therapy with a proton-pump inhibitor or were taking a selective cyclooxygenase-2 inhibitor.

SAN ANTONIO — Treating Helicobacter pylori infection in patients who take NSAIDs does not help prevent the development of peptic ulcer disease, Willem F. Lems, M.D., said at the annual meeting of the American College of Rheumatology.

In his study, 347 patients with culture-confirmed, H. pylori infection and a history of long-term NSAID use were randomized to receive H. pylori eradication treatment or a placebo.

Three months after treatment, peptic ulcers were diagnosed by endoscopy in 6 of 172 patients who had been actively treated, compared with 8 of 175 patients in the placebo group. One patient in the treated group and two patients in the placebo group developed endoscopic duodenal ulcers.

There was no significant difference between the groups in terms of the prevalence of gastroduodenal erosions (41 treated versus 51 placebo). Nor was there any difference in the rate of dyspepsia.

No patient in either group developed a symptomatic ulcer, an ulcer bleed, or ulcer perforation at any time during a full 12-month follow-up.

At the 3-month endoscopic examination, 87% of the treated patients and 21% of the placebo-treated patients were free of H. pylori.

The study adds to a body of literature on H. pylori and NSAID-associated ulcer that has been a bit confusing, said Dr. Lems of VU University Medical Center, Amsterdam.

While H. pylori eradication has been shown definitively to reduce ulcer recurrence in patients not taking NSAIDs, reports on what eradication does for patients on NSAIDs have been conflicting.

Although his study has the scientific strength of being a prospective trial, Dr. Lems said, it also could have been confounded by the fact that patients had to have been on long-term NSAID therapy already. His patients could have been a select group who were already able to tolerate NSAID treatment, and the results of treatment could be different for individuals just starting treatment.

A fairly large percentage of the patients (53%) were either on gastroprotective therapy with a proton-pump inhibitor or were taking a selective cyclooxygenase-2 inhibitor.

SAN ANTONIO — Treating Helicobacter pylori infection in patients who take NSAIDs does not help prevent the development of peptic ulcer disease, Willem F. Lems, M.D., said at the annual meeting of the American College of Rheumatology.

In his study, 347 patients with culture-confirmed, H. pylori infection and a history of long-term NSAID use were randomized to receive H. pylori eradication treatment or a placebo.

Three months after treatment, peptic ulcers were diagnosed by endoscopy in 6 of 172 patients who had been actively treated, compared with 8 of 175 patients in the placebo group. One patient in the treated group and two patients in the placebo group developed endoscopic duodenal ulcers.

There was no significant difference between the groups in terms of the prevalence of gastroduodenal erosions (41 treated versus 51 placebo). Nor was there any difference in the rate of dyspepsia.

No patient in either group developed a symptomatic ulcer, an ulcer bleed, or ulcer perforation at any time during a full 12-month follow-up.

At the 3-month endoscopic examination, 87% of the treated patients and 21% of the placebo-treated patients were free of H. pylori.

The study adds to a body of literature on H. pylori and NSAID-associated ulcer that has been a bit confusing, said Dr. Lems of VU University Medical Center, Amsterdam.

While H. pylori eradication has been shown definitively to reduce ulcer recurrence in patients not taking NSAIDs, reports on what eradication does for patients on NSAIDs have been conflicting.

Although his study has the scientific strength of being a prospective trial, Dr. Lems said, it also could have been confounded by the fact that patients had to have been on long-term NSAID therapy already. His patients could have been a select group who were already able to tolerate NSAID treatment, and the results of treatment could be different for individuals just starting treatment.

A fairly large percentage of the patients (53%) were either on gastroprotective therapy with a proton-pump inhibitor or were taking a selective cyclooxygenase-2 inhibitor.

SAN ANTONIO — Etanercept and infliximab do not appear to reduce responses to pneumococcal vaccination—but methotrexate treatment does, suggest the findings of a prospective trial conducted in Sweden.

Whenever possible, “rheumatoid arthritis patients should be vaccinated before starting methotrexate,” the lead investigator, Meliha Crnkic, M.D., advised at the annual meeting of the American College of Rheumatology.

Dr. Crnkic of Lund University Hospital and colleagues found that 50% of 62 rheumatoid arthritis patients receiving either etanercept or infliximab monotherapy had adequate responses to vaccination, defined as a twofold or better increase in immunoglobulin G antibody (23F and 6B) titers 4–6 weeks after vaccination.

By comparison, the response rate was 32% in 50 patients being treated with one of the biologics combined with methotrexate; 14% of the 37 patients receiving methotrexate monotherapy responded adequately. The difference between the response of the patients on biologic monotherapy and methotrexate monotherapy was statistically significant.

Among 47 healthy volunteers, 38% responded to vaccination. The difference in response rates between these controls and the patients on biologic monotherapy was not statistically significant. However, the healthy controls were slightly older as a group than the patients on the biologic agents alone, and, among the controls, age was shown to be factor in response, with the younger patients responding better, Dr. Crnkic noted.

Age did not appear to be a factor in response rates among patients taking the biologics, nor was gender, drug dosage, nor concurrent low-dose corticosteroid treatment.

It's not clear why the patients on combination treatment had a better response than the patients on methotrexate alone.

The study is the first prospective trial to investigate whether pneumococcal vaccination response is affected by treatment with a biologic agent. Previous reports had suggested that the agents did not cause a problem, Dr. Crnkic said.

SAN ANTONIO — Etanercept and infliximab do not appear to reduce responses to pneumococcal vaccination—but methotrexate treatment does, suggest the findings of a prospective trial conducted in Sweden.

Whenever possible, “rheumatoid arthritis patients should be vaccinated before starting methotrexate,” the lead investigator, Meliha Crnkic, M.D., advised at the annual meeting of the American College of Rheumatology.

Dr. Crnkic of Lund University Hospital and colleagues found that 50% of 62 rheumatoid arthritis patients receiving either etanercept or infliximab monotherapy had adequate responses to vaccination, defined as a twofold or better increase in immunoglobulin G antibody (23F and 6B) titers 4–6 weeks after vaccination.

By comparison, the response rate was 32% in 50 patients being treated with one of the biologics combined with methotrexate; 14% of the 37 patients receiving methotrexate monotherapy responded adequately. The difference between the response of the patients on biologic monotherapy and methotrexate monotherapy was statistically significant.

Among 47 healthy volunteers, 38% responded to vaccination. The difference in response rates between these controls and the patients on biologic monotherapy was not statistically significant. However, the healthy controls were slightly older as a group than the patients on the biologic agents alone, and, among the controls, age was shown to be factor in response, with the younger patients responding better, Dr. Crnkic noted.

Age did not appear to be a factor in response rates among patients taking the biologics, nor was gender, drug dosage, nor concurrent low-dose corticosteroid treatment.

It's not clear why the patients on combination treatment had a better response than the patients on methotrexate alone.

The study is the first prospective trial to investigate whether pneumococcal vaccination response is affected by treatment with a biologic agent. Previous reports had suggested that the agents did not cause a problem, Dr. Crnkic said.

SAN ANTONIO — Etanercept and infliximab do not appear to reduce responses to pneumococcal vaccination—but methotrexate treatment does, suggest the findings of a prospective trial conducted in Sweden.

Whenever possible, “rheumatoid arthritis patients should be vaccinated before starting methotrexate,” the lead investigator, Meliha Crnkic, M.D., advised at the annual meeting of the American College of Rheumatology.

Dr. Crnkic of Lund University Hospital and colleagues found that 50% of 62 rheumatoid arthritis patients receiving either etanercept or infliximab monotherapy had adequate responses to vaccination, defined as a twofold or better increase in immunoglobulin G antibody (23F and 6B) titers 4–6 weeks after vaccination.

By comparison, the response rate was 32% in 50 patients being treated with one of the biologics combined with methotrexate; 14% of the 37 patients receiving methotrexate monotherapy responded adequately. The difference between the response of the patients on biologic monotherapy and methotrexate monotherapy was statistically significant.

Among 47 healthy volunteers, 38% responded to vaccination. The difference in response rates between these controls and the patients on biologic monotherapy was not statistically significant. However, the healthy controls were slightly older as a group than the patients on the biologic agents alone, and, among the controls, age was shown to be factor in response, with the younger patients responding better, Dr. Crnkic noted.

Age did not appear to be a factor in response rates among patients taking the biologics, nor was gender, drug dosage, nor concurrent low-dose corticosteroid treatment.

It's not clear why the patients on combination treatment had a better response than the patients on methotrexate alone.

The study is the first prospective trial to investigate whether pneumococcal vaccination response is affected by treatment with a biologic agent. Previous reports had suggested that the agents did not cause a problem, Dr. Crnkic said.

VANCOUVER, B.C. — Simple measures taken at the time of ambulatory surgery, such as the use of clonidine, can significantly reduce patients' postprocedure pain, Dr. Scott S. Reuben said at the annual meeting of the American Pain Society.

On a scientific front, "there has been an explosion in our understanding of pain management in the past 4 or 5 years," said Dr. Reuben, director of the acute pain service at Baystate Medical Center, Springfield, Mass., at which 35,000 ambulatory surgeries are performed each year.

At the same time, surveys suggest that pain care following ambulatory surgery is not getting better and may even be getting somewhat worse, as the number and types of surgery have grown, Dr. Reuben said.

"We're doing a horrible job managing postoerative pain," he said.

Preemptive techniques are key to addressing this situation because it is now known that pain control before and during a surgical procedure can prevent the trauma from causing central sensitization, which lowers the pain threshold in the postoperative period.

Good short-term pain control may even prevent chronic, postoperative pain from developing, he said.

Some of the methods used at his center to preempt central sensitization include:

▸ Local analgesia. Even with general anesthesia, local pain control is important during surgery, Dr. Reuben said. "General anesthesia does nothing to block central sensitization of the nervous system. Local anesthetics can."

At his center, local anesthesia for joint surgery includes a combination of agents, clonidine, bupivacaine, and morphine. The surgeons use ice as well.

▸ Clonidine. Alpha2-agonists used locally cause vasoconstriction that prevents dispersion of other local anesthetics, and that is probably one reason clonidine has been shown to increase the duration of local bupivacaine action, by 20%–30% according to one study, Dr. Reuben said.

Clonidine itself also is an analgesic. It "has fantastic analgesic properties to control perioperative pain," he said.

▸ Opioids. The administration of an opioid before surgery acts centrally to prevent the hyperexcitability response produced by surgery, and this can mean less need for analgesics afterward. But more importantly, it is now known that there are local opioid receptors, and that even bone has them. "We have published about 12 studies on putting peripheral morphine in the knee for arthroscopy, with significant analgesic effects," Dr. Reuben said.

When morphine is used locally, very little is needed to control pain, and, as with clonidine, there appears to be a synergistic effect when it is used with other agents. Dr. Reuben's research group has shown that clonidine alone used locally produces significant analgesia for up to 7 hours, clonidine and bupivacaine produce analgesia for 10 hours, and clonidine, bupivacaine, and morphine combined produce 17 hours, he said.

VANCOUVER, B.C. — Simple measures taken at the time of ambulatory surgery, such as the use of clonidine, can significantly reduce patients' postprocedure pain, Dr. Scott S. Reuben said at the annual meeting of the American Pain Society.

On a scientific front, "there has been an explosion in our understanding of pain management in the past 4 or 5 years," said Dr. Reuben, director of the acute pain service at Baystate Medical Center, Springfield, Mass., at which 35,000 ambulatory surgeries are performed each year.

At the same time, surveys suggest that pain care following ambulatory surgery is not getting better and may even be getting somewhat worse, as the number and types of surgery have grown, Dr. Reuben said.

"We're doing a horrible job managing postoerative pain," he said.

Preemptive techniques are key to addressing this situation because it is now known that pain control before and during a surgical procedure can prevent the trauma from causing central sensitization, which lowers the pain threshold in the postoperative period.

Good short-term pain control may even prevent chronic, postoperative pain from developing, he said.

Some of the methods used at his center to preempt central sensitization include:

▸ Local analgesia. Even with general anesthesia, local pain control is important during surgery, Dr. Reuben said. "General anesthesia does nothing to block central sensitization of the nervous system. Local anesthetics can."

At his center, local anesthesia for joint surgery includes a combination of agents, clonidine, bupivacaine, and morphine. The surgeons use ice as well.

▸ Clonidine. Alpha2-agonists used locally cause vasoconstriction that prevents dispersion of other local anesthetics, and that is probably one reason clonidine has been shown to increase the duration of local bupivacaine action, by 20%–30% according to one study, Dr. Reuben said.

Clonidine itself also is an analgesic. It "has fantastic analgesic properties to control perioperative pain," he said.

▸ Opioids. The administration of an opioid before surgery acts centrally to prevent the hyperexcitability response produced by surgery, and this can mean less need for analgesics afterward. But more importantly, it is now known that there are local opioid receptors, and that even bone has them. "We have published about 12 studies on putting peripheral morphine in the knee for arthroscopy, with significant analgesic effects," Dr. Reuben said.

When morphine is used locally, very little is needed to control pain, and, as with clonidine, there appears to be a synergistic effect when it is used with other agents. Dr. Reuben's research group has shown that clonidine alone used locally produces significant analgesia for up to 7 hours, clonidine and bupivacaine produce analgesia for 10 hours, and clonidine, bupivacaine, and morphine combined produce 17 hours, he said.

VANCOUVER, B.C. — Simple measures taken at the time of ambulatory surgery, such as the use of clonidine, can significantly reduce patients' postprocedure pain, Dr. Scott S. Reuben said at the annual meeting of the American Pain Society.

On a scientific front, "there has been an explosion in our understanding of pain management in the past 4 or 5 years," said Dr. Reuben, director of the acute pain service at Baystate Medical Center, Springfield, Mass., at which 35,000 ambulatory surgeries are performed each year.

At the same time, surveys suggest that pain care following ambulatory surgery is not getting better and may even be getting somewhat worse, as the number and types of surgery have grown, Dr. Reuben said.

"We're doing a horrible job managing postoerative pain," he said.

Preemptive techniques are key to addressing this situation because it is now known that pain control before and during a surgical procedure can prevent the trauma from causing central sensitization, which lowers the pain threshold in the postoperative period.

Good short-term pain control may even prevent chronic, postoperative pain from developing, he said.

Some of the methods used at his center to preempt central sensitization include:

▸ Local analgesia. Even with general anesthesia, local pain control is important during surgery, Dr. Reuben said. "General anesthesia does nothing to block central sensitization of the nervous system. Local anesthetics can."

At his center, local anesthesia for joint surgery includes a combination of agents, clonidine, bupivacaine, and morphine. The surgeons use ice as well.

▸ Clonidine. Alpha2-agonists used locally cause vasoconstriction that prevents dispersion of other local anesthetics, and that is probably one reason clonidine has been shown to increase the duration of local bupivacaine action, by 20%–30% according to one study, Dr. Reuben said.

Clonidine itself also is an analgesic. It "has fantastic analgesic properties to control perioperative pain," he said.

▸ Opioids. The administration of an opioid before surgery acts centrally to prevent the hyperexcitability response produced by surgery, and this can mean less need for analgesics afterward. But more importantly, it is now known that there are local opioid receptors, and that even bone has them. "We have published about 12 studies on putting peripheral morphine in the knee for arthroscopy, with significant analgesic effects," Dr. Reuben said.

When morphine is used locally, very little is needed to control pain, and, as with clonidine, there appears to be a synergistic effect when it is used with other agents. Dr. Reuben's research group has shown that clonidine alone used locally produces significant analgesia for up to 7 hours, clonidine and bupivacaine produce analgesia for 10 hours, and clonidine, bupivacaine, and morphine combined produce 17 hours, he said.

PHOENIX, ARIZ. — Younger patients with even a thin melanoma may deserve a sentinel node biopsy because of a much higher likelihood of lymph node metastasis, regardless of any other histologic features, said Vernon K. Sondak, M.D., at the Second International Melanoma Research Congress.

Recent data suggest that a 35-year-old with a melanoma that is just 1 mm thick could have as high as a 20% chance of a positive node, said Dr. Sondak, a surgical oncologist at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

In a talk about sentinel node biopsy, Dr. Sondak defended the procedure as a useful clinical tool—despite disappointment that it does not make a bigger difference in survival—and said that its use probably needs to be expanded.

Currently, most major centers that treat melanoma use a cutoff of about 1–1.5 mm when deciding whether to have a patient undergo sentinel node biopsy. Yet about three-fourths of melanomas diagnosed in this country are less than 1 mm in thickness and at the same time, the absolute number of deaths from thin melanomas is increasing progressively, and the procedure might be a way to make a difference, Dr. Sondak said.

But costs are an issue. It has been estimated that to perform a sentinel node biopsy on every case of melanoma would cost almost $1 million for every patient with a positive node detected, he said.

Using Clark's level of invasion and/or the presence of ulceration as criteria to further winnow the pool of possible candidates for the procedure does not appear to work. Both ulceration and Clark's level predict outcome, but they do not predict positive nodes, Dr. Sondak said.

In previous investigations into predictive markers of risk, factors identified by some, but not all of the studies include younger age, a high mitotic rate, and the Breslow depth of invasion.

The first such study, from the John Wayne Cancer Institute in Santa Monica, Calif., reviewed 512 patients with melanomas less than 1.5 mm in thickness. The investigators reported that positive sentinel nodes were found in 7% of patients with a 1- to 1.5-mm melanoma, in 4% of patients with a 0.75- to 1-mm melanoma, and in 2% of patients with a melanoma thinner than 0.75 mm.

They also found that younger patients were more likely to have a positive node than were older patients.

Based on the results of that study, Dr. Sondak and his colleagues reviewed the records of 419 patients from a registry at the University of Michigan. Their melanomas had a range of thicknesses, and there were similar percentages with positive nodes among the thin melanomas.

This study also found the same connection with age. The percentage of patients older than 60 years who had a positive sentinel node was 12%, and the percentage rose to 19% for those aged 35–60 years and to 26% for those younger than 35 years (Ann. Surg. Oncol. 2004;11:247–58).

The investigators also found that a high mitotic rate—defined as at least 3 mitoses per square millimeter of the lesion—was associated with positive nodes, and was as predictive as the Breslow depth.

Another unpublished study appears to confirm the finding regarding mitotic rate. The study, reported by researchers at the University of Pennsylvania, specifically looked at patients with melanomas that were thin but had already entered a vertical growth phase. It included 167 consecutive patients who all had melanomas of 1 mm or less in thickness.

In those patients, one or more positive nodes were found in 11% of the patients with a melanoma that had a high mitotic rate, but none was found in patients with a low mitotic rate, Dr. Sondak said. The study also found no cases of a positive node in patients older than 60 years.

Although the data about age and mitotic rate are preliminary, Dr. Sondak said he already uses the information in his discussions with patients.

PHOENIX, ARIZ. — Younger patients with even a thin melanoma may deserve a sentinel node biopsy because of a much higher likelihood of lymph node metastasis, regardless of any other histologic features, said Vernon K. Sondak, M.D., at the Second International Melanoma Research Congress.

Recent data suggest that a 35-year-old with a melanoma that is just 1 mm thick could have as high as a 20% chance of a positive node, said Dr. Sondak, a surgical oncologist at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

In a talk about sentinel node biopsy, Dr. Sondak defended the procedure as a useful clinical tool—despite disappointment that it does not make a bigger difference in survival—and said that its use probably needs to be expanded.

Currently, most major centers that treat melanoma use a cutoff of about 1–1.5 mm when deciding whether to have a patient undergo sentinel node biopsy. Yet about three-fourths of melanomas diagnosed in this country are less than 1 mm in thickness and at the same time, the absolute number of deaths from thin melanomas is increasing progressively, and the procedure might be a way to make a difference, Dr. Sondak said.

But costs are an issue. It has been estimated that to perform a sentinel node biopsy on every case of melanoma would cost almost $1 million for every patient with a positive node detected, he said.

Using Clark's level of invasion and/or the presence of ulceration as criteria to further winnow the pool of possible candidates for the procedure does not appear to work. Both ulceration and Clark's level predict outcome, but they do not predict positive nodes, Dr. Sondak said.

In previous investigations into predictive markers of risk, factors identified by some, but not all of the studies include younger age, a high mitotic rate, and the Breslow depth of invasion.

The first such study, from the John Wayne Cancer Institute in Santa Monica, Calif., reviewed 512 patients with melanomas less than 1.5 mm in thickness. The investigators reported that positive sentinel nodes were found in 7% of patients with a 1- to 1.5-mm melanoma, in 4% of patients with a 0.75- to 1-mm melanoma, and in 2% of patients with a melanoma thinner than 0.75 mm.

They also found that younger patients were more likely to have a positive node than were older patients.

Based on the results of that study, Dr. Sondak and his colleagues reviewed the records of 419 patients from a registry at the University of Michigan. Their melanomas had a range of thicknesses, and there were similar percentages with positive nodes among the thin melanomas.

This study also found the same connection with age. The percentage of patients older than 60 years who had a positive sentinel node was 12%, and the percentage rose to 19% for those aged 35–60 years and to 26% for those younger than 35 years (Ann. Surg. Oncol. 2004;11:247–58).

The investigators also found that a high mitotic rate—defined as at least 3 mitoses per square millimeter of the lesion—was associated with positive nodes, and was as predictive as the Breslow depth.

Another unpublished study appears to confirm the finding regarding mitotic rate. The study, reported by researchers at the University of Pennsylvania, specifically looked at patients with melanomas that were thin but had already entered a vertical growth phase. It included 167 consecutive patients who all had melanomas of 1 mm or less in thickness.

In those patients, one or more positive nodes were found in 11% of the patients with a melanoma that had a high mitotic rate, but none was found in patients with a low mitotic rate, Dr. Sondak said. The study also found no cases of a positive node in patients older than 60 years.

Although the data about age and mitotic rate are preliminary, Dr. Sondak said he already uses the information in his discussions with patients.

PHOENIX, ARIZ. — Younger patients with even a thin melanoma may deserve a sentinel node biopsy because of a much higher likelihood of lymph node metastasis, regardless of any other histologic features, said Vernon K. Sondak, M.D., at the Second International Melanoma Research Congress.

Recent data suggest that a 35-year-old with a melanoma that is just 1 mm thick could have as high as a 20% chance of a positive node, said Dr. Sondak, a surgical oncologist at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

In a talk about sentinel node biopsy, Dr. Sondak defended the procedure as a useful clinical tool—despite disappointment that it does not make a bigger difference in survival—and said that its use probably needs to be expanded.

Currently, most major centers that treat melanoma use a cutoff of about 1–1.5 mm when deciding whether to have a patient undergo sentinel node biopsy. Yet about three-fourths of melanomas diagnosed in this country are less than 1 mm in thickness and at the same time, the absolute number of deaths from thin melanomas is increasing progressively, and the procedure might be a way to make a difference, Dr. Sondak said.

But costs are an issue. It has been estimated that to perform a sentinel node biopsy on every case of melanoma would cost almost $1 million for every patient with a positive node detected, he said.

Using Clark's level of invasion and/or the presence of ulceration as criteria to further winnow the pool of possible candidates for the procedure does not appear to work. Both ulceration and Clark's level predict outcome, but they do not predict positive nodes, Dr. Sondak said.

In previous investigations into predictive markers of risk, factors identified by some, but not all of the studies include younger age, a high mitotic rate, and the Breslow depth of invasion.

The first such study, from the John Wayne Cancer Institute in Santa Monica, Calif., reviewed 512 patients with melanomas less than 1.5 mm in thickness. The investigators reported that positive sentinel nodes were found in 7% of patients with a 1- to 1.5-mm melanoma, in 4% of patients with a 0.75- to 1-mm melanoma, and in 2% of patients with a melanoma thinner than 0.75 mm.

They also found that younger patients were more likely to have a positive node than were older patients.

Based on the results of that study, Dr. Sondak and his colleagues reviewed the records of 419 patients from a registry at the University of Michigan. Their melanomas had a range of thicknesses, and there were similar percentages with positive nodes among the thin melanomas.

This study also found the same connection with age. The percentage of patients older than 60 years who had a positive sentinel node was 12%, and the percentage rose to 19% for those aged 35–60 years and to 26% for those younger than 35 years (Ann. Surg. Oncol. 2004;11:247–58).

The investigators also found that a high mitotic rate—defined as at least 3 mitoses per square millimeter of the lesion—was associated with positive nodes, and was as predictive as the Breslow depth.

Another unpublished study appears to confirm the finding regarding mitotic rate. The study, reported by researchers at the University of Pennsylvania, specifically looked at patients with melanomas that were thin but had already entered a vertical growth phase. It included 167 consecutive patients who all had melanomas of 1 mm or less in thickness.

In those patients, one or more positive nodes were found in 11% of the patients with a melanoma that had a high mitotic rate, but none was found in patients with a low mitotic rate, Dr. Sondak said. The study also found no cases of a positive node in patients older than 60 years.

Although the data about age and mitotic rate are preliminary, Dr. Sondak said he already uses the information in his discussions with patients.

SAN ANTONIO — Oral contraceptive use appears to be inversely associated with being rheumatoid-factor positive, Kevin D. Deane, M.D., said in a poster presentation at the annual meeting of the American College of Rheumatology.

In his study, 90% of 256 women had used an oral contraceptive at some time and 10% were positive for rheumatoid factor. The odds ratio of a woman being positive for rheumatoid factor was 0.18 if she had used oral contraceptives.

The women were mothers of children selected as part of an investigation into the heritability of type 1 diabetes. They were chosen for the study because of the likelihood of their having the HLA-DR4 allele, which is associated with both diabetes and rheumatoid arthritis.

Among the other factors examined were breast-feeding; use of nicotine, coffee, and injectable hormones; and age. None of these factors had as strong an association—either positively or negatively—as the use of oral contraception, said Dr. Deane of the University of Colorado, Denver.

The results “are significant statistically,” Dr. Keane said in an interview.

He noted that higher endogenous estrogen levels have been shown to correlate somewhat with a lower incidence of rheumatoid arthritis, and that a decrease in those levels could predispose a woman to vulnerability.

Although Dr. Deane admitted that his findings are merely an intriguing observation, he added that if patients have another reason to take an OC, it's not unreasonable to tell them about the potential for arthritis prevention as an added benefit.

SAN ANTONIO — Oral contraceptive use appears to be inversely associated with being rheumatoid-factor positive, Kevin D. Deane, M.D., said in a poster presentation at the annual meeting of the American College of Rheumatology.

In his study, 90% of 256 women had used an oral contraceptive at some time and 10% were positive for rheumatoid factor. The odds ratio of a woman being positive for rheumatoid factor was 0.18 if she had used oral contraceptives.

The women were mothers of children selected as part of an investigation into the heritability of type 1 diabetes. They were chosen for the study because of the likelihood of their having the HLA-DR4 allele, which is associated with both diabetes and rheumatoid arthritis.

Among the other factors examined were breast-feeding; use of nicotine, coffee, and injectable hormones; and age. None of these factors had as strong an association—either positively or negatively—as the use of oral contraception, said Dr. Deane of the University of Colorado, Denver.

The results “are significant statistically,” Dr. Keane said in an interview.

He noted that higher endogenous estrogen levels have been shown to correlate somewhat with a lower incidence of rheumatoid arthritis, and that a decrease in those levels could predispose a woman to vulnerability.

Although Dr. Deane admitted that his findings are merely an intriguing observation, he added that if patients have another reason to take an OC, it's not unreasonable to tell them about the potential for arthritis prevention as an added benefit.

SAN ANTONIO — Oral contraceptive use appears to be inversely associated with being rheumatoid-factor positive, Kevin D. Deane, M.D., said in a poster presentation at the annual meeting of the American College of Rheumatology.

In his study, 90% of 256 women had used an oral contraceptive at some time and 10% were positive for rheumatoid factor. The odds ratio of a woman being positive for rheumatoid factor was 0.18 if she had used oral contraceptives.

The women were mothers of children selected as part of an investigation into the heritability of type 1 diabetes. They were chosen for the study because of the likelihood of their having the HLA-DR4 allele, which is associated with both diabetes and rheumatoid arthritis.

Among the other factors examined were breast-feeding; use of nicotine, coffee, and injectable hormones; and age. None of these factors had as strong an association—either positively or negatively—as the use of oral contraception, said Dr. Deane of the University of Colorado, Denver.

The results “are significant statistically,” Dr. Keane said in an interview.

He noted that higher endogenous estrogen levels have been shown to correlate somewhat with a lower incidence of rheumatoid arthritis, and that a decrease in those levels could predispose a woman to vulnerability.

Although Dr. Deane admitted that his findings are merely an intriguing observation, he added that if patients have another reason to take an OC, it's not unreasonable to tell them about the potential for arthritis prevention as an added benefit.

SAN ANTONIO — A clinical trial undertaken to evaluate etanercept tolerance by rheumatoid arthritis patients with comorbid conditions was stopped early because there were too few adverse events and infections to analyze, Scott W. Baumgartner, M.D., said at the annual meeting of the American College of Rheumatology.

The purpose of the study was to determine whether etanercept (Enbrel) use in patients with conditions such as diabetes might make them more prone to infections than has been suggested with initial trials of anti-tumor necrosis factor therapy, said Dr. Baumgartner, a private-practice researcher in Spokane, Wash.

The double-blind, placebo-controlled trial was to enroll 1,000 individuals, including 200 with diabetes, who would be treated and followed for 20 weeks each. After 535 patients were enrolled and treated, however, the data-monitoring safety board halted the trial, mainly because the infection rate was similar in both groups and the board believed that this result was unlikely to change.

At the same time, the trial researchers were having trouble recruiting subjects, since some people were reluctant to be assigned to placebo. Amgen Inc., the study sponsor, conferred with the Food and Drug Administration before canceling the study.

The majority of subjects in the study had either chronic obstructive pulmonary disease (42%) or diabetes (40%).

More subjects on placebo discontinued than did those on etanercept: 53 of 269 subjects compared with 29 of 266 subjects, respectively. The incidence of patients withdrawing specifically because of adverse events was 6% for placebo and 5% for etanercept.

The incidence of medically important infections in the study was 3.7% for placebo and 3.4% for etanercept. “And the types of infections seen were pretty similar, a few more [urinary tract infections] in the etanercept group and a few more [upper respiratory infections] in the placebo group,” Dr. Baumgartner said.

The deaths of four patients in the etanercept group and one patient in the placebo group appeared to be unrelated to the drug because the patients were very ill, Dr. Baumgartner said. Two patients died from coronary events, one from a subarachnoid hemorrhage, and one from respiratory failure.

SAN ANTONIO — A clinical trial undertaken to evaluate etanercept tolerance by rheumatoid arthritis patients with comorbid conditions was stopped early because there were too few adverse events and infections to analyze, Scott W. Baumgartner, M.D., said at the annual meeting of the American College of Rheumatology.

The purpose of the study was to determine whether etanercept (Enbrel) use in patients with conditions such as diabetes might make them more prone to infections than has been suggested with initial trials of anti-tumor necrosis factor therapy, said Dr. Baumgartner, a private-practice researcher in Spokane, Wash.

The double-blind, placebo-controlled trial was to enroll 1,000 individuals, including 200 with diabetes, who would be treated and followed for 20 weeks each. After 535 patients were enrolled and treated, however, the data-monitoring safety board halted the trial, mainly because the infection rate was similar in both groups and the board believed that this result was unlikely to change.

At the same time, the trial researchers were having trouble recruiting subjects, since some people were reluctant to be assigned to placebo. Amgen Inc., the study sponsor, conferred with the Food and Drug Administration before canceling the study.

The majority of subjects in the study had either chronic obstructive pulmonary disease (42%) or diabetes (40%).

More subjects on placebo discontinued than did those on etanercept: 53 of 269 subjects compared with 29 of 266 subjects, respectively. The incidence of patients withdrawing specifically because of adverse events was 6% for placebo and 5% for etanercept.

The incidence of medically important infections in the study was 3.7% for placebo and 3.4% for etanercept. “And the types of infections seen were pretty similar, a few more [urinary tract infections] in the etanercept group and a few more [upper respiratory infections] in the placebo group,” Dr. Baumgartner said.

The deaths of four patients in the etanercept group and one patient in the placebo group appeared to be unrelated to the drug because the patients were very ill, Dr. Baumgartner said. Two patients died from coronary events, one from a subarachnoid hemorrhage, and one from respiratory failure.

SAN ANTONIO — A clinical trial undertaken to evaluate etanercept tolerance by rheumatoid arthritis patients with comorbid conditions was stopped early because there were too few adverse events and infections to analyze, Scott W. Baumgartner, M.D., said at the annual meeting of the American College of Rheumatology.

The purpose of the study was to determine whether etanercept (Enbrel) use in patients with conditions such as diabetes might make them more prone to infections than has been suggested with initial trials of anti-tumor necrosis factor therapy, said Dr. Baumgartner, a private-practice researcher in Spokane, Wash.

The double-blind, placebo-controlled trial was to enroll 1,000 individuals, including 200 with diabetes, who would be treated and followed for 20 weeks each. After 535 patients were enrolled and treated, however, the data-monitoring safety board halted the trial, mainly because the infection rate was similar in both groups and the board believed that this result was unlikely to change.

At the same time, the trial researchers were having trouble recruiting subjects, since some people were reluctant to be assigned to placebo. Amgen Inc., the study sponsor, conferred with the Food and Drug Administration before canceling the study.

The majority of subjects in the study had either chronic obstructive pulmonary disease (42%) or diabetes (40%).

More subjects on placebo discontinued than did those on etanercept: 53 of 269 subjects compared with 29 of 266 subjects, respectively. The incidence of patients withdrawing specifically because of adverse events was 6% for placebo and 5% for etanercept.

The incidence of medically important infections in the study was 3.7% for placebo and 3.4% for etanercept. “And the types of infections seen were pretty similar, a few more [urinary tract infections] in the etanercept group and a few more [upper respiratory infections] in the placebo group,” Dr. Baumgartner said.

The deaths of four patients in the etanercept group and one patient in the placebo group appeared to be unrelated to the drug because the patients were very ill, Dr. Baumgartner said. Two patients died from coronary events, one from a subarachnoid hemorrhage, and one from respiratory failure.

SEATTLE — Alendronate appears slightly more effective than risedronate at increasing bone mineral density, according to the results of a head-to-head trial presented during the annual meeting of the American Society for Bone and Mineral Research.

However, without fracture data, it's unknown whether such BMD findings will translate into a clinically meaningful difference.

In the double-blinded study involving 1,053 postmenopausal women treated for 1 year, alendronate increased BMD at the hip trochanter by a mean of 3.4%, and risedronate increased trochanter BMD by a mean of 2.1%.

The investigation, known as the Fosamax Actonel Comparison Trial, was conducted with patients from 78 different centers, said Clifford J. Rosen, M.D., who is the director of the Maine Center of Osteoporosis Research and Education, Bangor.

Patients received either 70 mg of alendronate and placebo risedronate once weekly or 35 mg risedronate and placebo alendronate once weekly.

In addition to the hip trochanter, BMD measurements were taken for the total hip, lumbar spine, and femoral neck. BMD was increased a mean 2.2% in the active alendronate group, versus a mean 1.2% in the active risedronate group.

Lumbar spine BMD increased a mean 3.7% with alendronate, versus 2.6% with risedronate. In addition, femoral neck BMD increased a mean 1.6% with alendronate and 0.9% with risedronate, he said.

A greater proportion of patients also either maintained or increased BMD on alendronate. Of the patients on alendronate, 84% at least maintained trochanter BMD and 51% had at least a 3% increase, whereas on risedronate, 68% of patients at least maintained BMD, and 41% had a 3% increase or greater.

In addition, alendronate depressed urine and serum markers of bone turnover to a greater degree than risedronate. There was no difference in the occurrence of adverse events between the two drugs.

Not everyone at the meeting was impressed by the study or its results.

“Marketing,” said Paul D. Miller, M.D., when asked about the trial, which was sponsored by Merck and Co., Inc., the manufacturer of alendronate. It's not clear that the degree of difference reported translates into greater bone strength, he said.

“The problem is that there are no fracture data,” said Dr. Miller, medical director for the Colorado Center for Bone Research, Lakewood. “At these differences, the bone strength may not be very different.”

A larger study over a longer period of time would be needed to acquire fracture data, said Richard Petruschke, Pharm. D., who is a spokesperson for Merck and one of the investigators in the study.

“There is literature to support using these surrogates as being meaningful when taken together,” Dr. Petruschke commented.

SEATTLE — Alendronate appears slightly more effective than risedronate at increasing bone mineral density, according to the results of a head-to-head trial presented during the annual meeting of the American Society for Bone and Mineral Research.

However, without fracture data, it's unknown whether such BMD findings will translate into a clinically meaningful difference.

In the double-blinded study involving 1,053 postmenopausal women treated for 1 year, alendronate increased BMD at the hip trochanter by a mean of 3.4%, and risedronate increased trochanter BMD by a mean of 2.1%.

The investigation, known as the Fosamax Actonel Comparison Trial, was conducted with patients from 78 different centers, said Clifford J. Rosen, M.D., who is the director of the Maine Center of Osteoporosis Research and Education, Bangor.

Patients received either 70 mg of alendronate and placebo risedronate once weekly or 35 mg risedronate and placebo alendronate once weekly.

In addition to the hip trochanter, BMD measurements were taken for the total hip, lumbar spine, and femoral neck. BMD was increased a mean 2.2% in the active alendronate group, versus a mean 1.2% in the active risedronate group.

Lumbar spine BMD increased a mean 3.7% with alendronate, versus 2.6% with risedronate. In addition, femoral neck BMD increased a mean 1.6% with alendronate and 0.9% with risedronate, he said.

A greater proportion of patients also either maintained or increased BMD on alendronate. Of the patients on alendronate, 84% at least maintained trochanter BMD and 51% had at least a 3% increase, whereas on risedronate, 68% of patients at least maintained BMD, and 41% had a 3% increase or greater.

In addition, alendronate depressed urine and serum markers of bone turnover to a greater degree than risedronate. There was no difference in the occurrence of adverse events between the two drugs.

Not everyone at the meeting was impressed by the study or its results.

“Marketing,” said Paul D. Miller, M.D., when asked about the trial, which was sponsored by Merck and Co., Inc., the manufacturer of alendronate. It's not clear that the degree of difference reported translates into greater bone strength, he said.

“The problem is that there are no fracture data,” said Dr. Miller, medical director for the Colorado Center for Bone Research, Lakewood. “At these differences, the bone strength may not be very different.”

A larger study over a longer period of time would be needed to acquire fracture data, said Richard Petruschke, Pharm. D., who is a spokesperson for Merck and one of the investigators in the study.

“There is literature to support using these surrogates as being meaningful when taken together,” Dr. Petruschke commented.

SEATTLE — Alendronate appears slightly more effective than risedronate at increasing bone mineral density, according to the results of a head-to-head trial presented during the annual meeting of the American Society for Bone and Mineral Research.

However, without fracture data, it's unknown whether such BMD findings will translate into a clinically meaningful difference.

In the double-blinded study involving 1,053 postmenopausal women treated for 1 year, alendronate increased BMD at the hip trochanter by a mean of 3.4%, and risedronate increased trochanter BMD by a mean of 2.1%.

The investigation, known as the Fosamax Actonel Comparison Trial, was conducted with patients from 78 different centers, said Clifford J. Rosen, M.D., who is the director of the Maine Center of Osteoporosis Research and Education, Bangor.

Patients received either 70 mg of alendronate and placebo risedronate once weekly or 35 mg risedronate and placebo alendronate once weekly.

In addition to the hip trochanter, BMD measurements were taken for the total hip, lumbar spine, and femoral neck. BMD was increased a mean 2.2% in the active alendronate group, versus a mean 1.2% in the active risedronate group.

Lumbar spine BMD increased a mean 3.7% with alendronate, versus 2.6% with risedronate. In addition, femoral neck BMD increased a mean 1.6% with alendronate and 0.9% with risedronate, he said.

A greater proportion of patients also either maintained or increased BMD on alendronate. Of the patients on alendronate, 84% at least maintained trochanter BMD and 51% had at least a 3% increase, whereas on risedronate, 68% of patients at least maintained BMD, and 41% had a 3% increase or greater.

In addition, alendronate depressed urine and serum markers of bone turnover to a greater degree than risedronate. There was no difference in the occurrence of adverse events between the two drugs.

Not everyone at the meeting was impressed by the study or its results.

“Marketing,” said Paul D. Miller, M.D., when asked about the trial, which was sponsored by Merck and Co., Inc., the manufacturer of alendronate. It's not clear that the degree of difference reported translates into greater bone strength, he said.

“The problem is that there are no fracture data,” said Dr. Miller, medical director for the Colorado Center for Bone Research, Lakewood. “At these differences, the bone strength may not be very different.”

A larger study over a longer period of time would be needed to acquire fracture data, said Richard Petruschke, Pharm. D., who is a spokesperson for Merck and one of the investigators in the study.

“There is literature to support using these surrogates as being meaningful when taken together,” Dr. Petruschke commented.