Timothy F. Kirn

SAN DIEGO – Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm.

However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups–28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group–even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked.

The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

“I would conclude we don't need to be checking vitamin D levels in patients with fibromyalgia,” Dr. Warner said.

SAN DIEGO – Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm.

However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups–28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group–even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked.

The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

“I would conclude we don't need to be checking vitamin D levels in patients with fibromyalgia,” Dr. Warner said.

SAN DIEGO – Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm.

However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups–28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group–even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked.

The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

“I would conclude we don't need to be checking vitamin D levels in patients with fibromyalgia,” Dr. Warner said.

SCOTTSDALE, ARIZ. – Opiate addicts who go through withdrawal using buprenorphine are nine times more likely to complete their withdrawal regimen than are patients who use clonidine, a large National Institute on Drug Abuse-sponsored trial shows.

In addition, buprenorphine might be that much-sought-after key to getting more opiate abusers invested in their longer-term psychotherapy treatment, Leslie Amass, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The study involved 344 opiate-addicted subjects who were randomized to either a 13-day schedule of tapered withdrawal using buprenorphine-naloxone (Suboxone) or a tapered withdrawal using clonidine patches. The patients came from 12 centers; 113 patients were detoxified as inpatients and 231 as outpatients. Most were heroin abusers, and many had been in treatment before.

No problems were found with the early doses of buprenorphine. All of the patients took and tolerated their first day's dose of 8 mg, and 90% completed the induction phase of treatment. During that phase, the dose was increased to 16 mg before being cut back, said Dr. Amass, a principal investigator with the Friends Research Institute Inc., Los Angeles.

Overall, 68% of the buprenorphine-detoxified patients completed the full process, compared with only 30% of the clonidine patients.

Moreover, 77% of the inpatient, buprenorphine-detoxified patients completed and tested negative for illicit opiate use on day 14, compared with 22% of the inpatient, clonidine-detoxified patients. The same was true for 29% of the buprenorphine-treated outpatients and 5% of the clonidine-treated outpatients.

Fewer adverse events occurred in the buprenorphine-treated patients, and most were related to withdrawal. They included insomnia (62%), arthralgia (54%), and anxiety (52%). Only one of the serious adverse events was deemed potentially related to buprenorphine: a case of hematemesis that might have been a general opioid reaction.

“The big message here is that if you are going to pursue a short-term intervention focused on medical withdrawal for opiate addiction, buprenorphine is the way to go,” Dr. Amass said.

Longer follow-up of these patients has been difficult, as is typical with drug-treatment patients. But there is good reason to think that buprenorphine serves as a better bridge to long-term treatment for more patients, Dr. Amass said.

Several studies have tried to document this influence, including a recently reported investigation that followed adolescents. The study found that almost two-thirds of the adolescents treated with buprenorphine alone completed a 4-week course and transferred to naloxone maintenance. But only 5% of those treated with clonidine had done so (Arch. Gen. Psychiatry 2005;62:1157–64).

“That's unheard of in the treatment of adolescents,” Dr. Amass said.

The centers involved in the National Institute on Drug Abuse study had such a positive experience with buprenorphine and have become so convinced it leads to long-term treatment that almost all have continued their programs, she said.

The exceptions have been the study's methadone clinics, which are legally prohibited from changing drug treatments.

Two of the centers that have continued with buprenorphine are very prominent treatment centers that previously have eschewed pharmacologic detoxification of this kind: the Betty Ford Center in Rancho Mirage, Calif., and Phoenix House in New York.

Phoenix House notes that, of the first group of patients admitted to its buprenorphine withdrawal program, 90% completed detoxification and 76% continued into long-term treatment.

In a coordinated study at Phoenix House, almost 50% of 38 patients admitted to the program, completed a full 3-month treatment regimen. That compared with about 60% of 37 nonopiate drug abusers. Historically, the retention rate of opiate users is significantly lower than that of other drug or alcohol abusers.

The staff at Phoenix House attributes its better retention partly to the condition of its patients during the initial days of their stays. Phoenix House patients tend to be well enough during those early days to absorb the message delivered by counselors that recovery requires more than simply detoxification, Dr. Amass said.

The remaining contribution to retention probably has to do with the pharmacology of buprenorphine.

Buprenorphine “is the single best predictor of retention, regardless of setting,” Dr. Amass said.

SCOTTSDALE, ARIZ. – Opiate addicts who go through withdrawal using buprenorphine are nine times more likely to complete their withdrawal regimen than are patients who use clonidine, a large National Institute on Drug Abuse-sponsored trial shows.

In addition, buprenorphine might be that much-sought-after key to getting more opiate abusers invested in their longer-term psychotherapy treatment, Leslie Amass, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The study involved 344 opiate-addicted subjects who were randomized to either a 13-day schedule of tapered withdrawal using buprenorphine-naloxone (Suboxone) or a tapered withdrawal using clonidine patches. The patients came from 12 centers; 113 patients were detoxified as inpatients and 231 as outpatients. Most were heroin abusers, and many had been in treatment before.

No problems were found with the early doses of buprenorphine. All of the patients took and tolerated their first day's dose of 8 mg, and 90% completed the induction phase of treatment. During that phase, the dose was increased to 16 mg before being cut back, said Dr. Amass, a principal investigator with the Friends Research Institute Inc., Los Angeles.

Overall, 68% of the buprenorphine-detoxified patients completed the full process, compared with only 30% of the clonidine patients.

Moreover, 77% of the inpatient, buprenorphine-detoxified patients completed and tested negative for illicit opiate use on day 14, compared with 22% of the inpatient, clonidine-detoxified patients. The same was true for 29% of the buprenorphine-treated outpatients and 5% of the clonidine-treated outpatients.

Fewer adverse events occurred in the buprenorphine-treated patients, and most were related to withdrawal. They included insomnia (62%), arthralgia (54%), and anxiety (52%). Only one of the serious adverse events was deemed potentially related to buprenorphine: a case of hematemesis that might have been a general opioid reaction.

“The big message here is that if you are going to pursue a short-term intervention focused on medical withdrawal for opiate addiction, buprenorphine is the way to go,” Dr. Amass said.

Longer follow-up of these patients has been difficult, as is typical with drug-treatment patients. But there is good reason to think that buprenorphine serves as a better bridge to long-term treatment for more patients, Dr. Amass said.

Several studies have tried to document this influence, including a recently reported investigation that followed adolescents. The study found that almost two-thirds of the adolescents treated with buprenorphine alone completed a 4-week course and transferred to naloxone maintenance. But only 5% of those treated with clonidine had done so (Arch. Gen. Psychiatry 2005;62:1157–64).

“That's unheard of in the treatment of adolescents,” Dr. Amass said.

The centers involved in the National Institute on Drug Abuse study had such a positive experience with buprenorphine and have become so convinced it leads to long-term treatment that almost all have continued their programs, she said.

The exceptions have been the study's methadone clinics, which are legally prohibited from changing drug treatments.

Two of the centers that have continued with buprenorphine are very prominent treatment centers that previously have eschewed pharmacologic detoxification of this kind: the Betty Ford Center in Rancho Mirage, Calif., and Phoenix House in New York.

Phoenix House notes that, of the first group of patients admitted to its buprenorphine withdrawal program, 90% completed detoxification and 76% continued into long-term treatment.

In a coordinated study at Phoenix House, almost 50% of 38 patients admitted to the program, completed a full 3-month treatment regimen. That compared with about 60% of 37 nonopiate drug abusers. Historically, the retention rate of opiate users is significantly lower than that of other drug or alcohol abusers.

The staff at Phoenix House attributes its better retention partly to the condition of its patients during the initial days of their stays. Phoenix House patients tend to be well enough during those early days to absorb the message delivered by counselors that recovery requires more than simply detoxification, Dr. Amass said.

The remaining contribution to retention probably has to do with the pharmacology of buprenorphine.

Buprenorphine “is the single best predictor of retention, regardless of setting,” Dr. Amass said.

SCOTTSDALE, ARIZ. – Opiate addicts who go through withdrawal using buprenorphine are nine times more likely to complete their withdrawal regimen than are patients who use clonidine, a large National Institute on Drug Abuse-sponsored trial shows.

In addition, buprenorphine might be that much-sought-after key to getting more opiate abusers invested in their longer-term psychotherapy treatment, Leslie Amass, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The study involved 344 opiate-addicted subjects who were randomized to either a 13-day schedule of tapered withdrawal using buprenorphine-naloxone (Suboxone) or a tapered withdrawal using clonidine patches. The patients came from 12 centers; 113 patients were detoxified as inpatients and 231 as outpatients. Most were heroin abusers, and many had been in treatment before.

No problems were found with the early doses of buprenorphine. All of the patients took and tolerated their first day's dose of 8 mg, and 90% completed the induction phase of treatment. During that phase, the dose was increased to 16 mg before being cut back, said Dr. Amass, a principal investigator with the Friends Research Institute Inc., Los Angeles.

Overall, 68% of the buprenorphine-detoxified patients completed the full process, compared with only 30% of the clonidine patients.

Moreover, 77% of the inpatient, buprenorphine-detoxified patients completed and tested negative for illicit opiate use on day 14, compared with 22% of the inpatient, clonidine-detoxified patients. The same was true for 29% of the buprenorphine-treated outpatients and 5% of the clonidine-treated outpatients.

Fewer adverse events occurred in the buprenorphine-treated patients, and most were related to withdrawal. They included insomnia (62%), arthralgia (54%), and anxiety (52%). Only one of the serious adverse events was deemed potentially related to buprenorphine: a case of hematemesis that might have been a general opioid reaction.

“The big message here is that if you are going to pursue a short-term intervention focused on medical withdrawal for opiate addiction, buprenorphine is the way to go,” Dr. Amass said.

Longer follow-up of these patients has been difficult, as is typical with drug-treatment patients. But there is good reason to think that buprenorphine serves as a better bridge to long-term treatment for more patients, Dr. Amass said.

Several studies have tried to document this influence, including a recently reported investigation that followed adolescents. The study found that almost two-thirds of the adolescents treated with buprenorphine alone completed a 4-week course and transferred to naloxone maintenance. But only 5% of those treated with clonidine had done so (Arch. Gen. Psychiatry 2005;62:1157–64).

“That's unheard of in the treatment of adolescents,” Dr. Amass said.

The centers involved in the National Institute on Drug Abuse study had such a positive experience with buprenorphine and have become so convinced it leads to long-term treatment that almost all have continued their programs, she said.

The exceptions have been the study's methadone clinics, which are legally prohibited from changing drug treatments.

Two of the centers that have continued with buprenorphine are very prominent treatment centers that previously have eschewed pharmacologic detoxification of this kind: the Betty Ford Center in Rancho Mirage, Calif., and Phoenix House in New York.

Phoenix House notes that, of the first group of patients admitted to its buprenorphine withdrawal program, 90% completed detoxification and 76% continued into long-term treatment.

In a coordinated study at Phoenix House, almost 50% of 38 patients admitted to the program, completed a full 3-month treatment regimen. That compared with about 60% of 37 nonopiate drug abusers. Historically, the retention rate of opiate users is significantly lower than that of other drug or alcohol abusers.

The staff at Phoenix House attributes its better retention partly to the condition of its patients during the initial days of their stays. Phoenix House patients tend to be well enough during those early days to absorb the message delivered by counselors that recovery requires more than simply detoxification, Dr. Amass said.

The remaining contribution to retention probably has to do with the pharmacology of buprenorphine.

Buprenorphine “is the single best predictor of retention, regardless of setting,” Dr. Amass said.

SCOTTSDALE, ARIZ. – At a recent workshop on office buprenorphine prescribing, the first question addressed was: Is the 30-patient limit likely to be revised?

The urgency of the question is another sign that physicians who choose to become waiver-qualified to treat patients addicted to narcotics under the Drug Addiction Treatment Act of 2000 continue to find that the demand surpasses their ability to provide care.

Currently, about 5,000 physicians have the waiver to prescribe buprenorphine for addiction treatment, said Dr. Laura F. McNicholas, who led the workshop, which was held at the annual meeting of the American Academy of Addiction Psychiatry. It has been reported that fewer than half that number regularly prescribe, however.

Those who do prescribe tend to be swamped with patients. Many of the specialists who attended the workshop mentioned that they would like to be able to refer patients they have gotten stabilized to create more room on their rosters, but they have been unable to find other physicians to take those patients.

Last year, federal officials relaxed the limit set on the number of patients who could be treated from 30 patients at any one site to 30 patients per waiver-qualified physician. This has led many to question whether further relaxation is forthcoming.

Among those familiar with the machinations of the federal government, the sense is that Congress may be amenable to the idea of loosening the limits further because federal officials are satisfied with the way the program has been working.

But some limits will stay be in place, at least for the time being, said Dr. McNicholas, who recently chaired a panel that developed office buprenorphine guidelines for the Substance Abuse and Mental Health Services Administration.

The medical groups involved have not come to a consensus about the new limits they should seek from Congress, but discussions have begun, she added.

A recent assessment document on the buprenorphine prescribing program shows that even the Drug Enforcement Agency is satisfied with the program, said Dr. McNicholas, of the University of Pennsylvania Treatment Research Center, Philadelphia.

The document, which has been discussed but not yet finalized or published, says that, as expected, the program is reaching a different demographic of narcotics addicts than has traditionally been involved with methadone programs and other kinds of treatment. Those prescribed buprenorphine are more middle class and less likely to be addicted to heroin.

Figures in the report, which covers 3 years, indicate that about 60% of the patients treated through the program had never been in drug treatment before, and about 40% had been abusing diverted prescription medications, such as OxyContin, Dr. McNicholas said.

The report also says that while there has been diversion of buprenorphine, it does not appear to be a major problem. In fact, it notes that many of the cases have involved patients giving the medication to friends, who then find it so efficacious that they seek out treatment for themselves.

Another topic of discussion during the workshop involved the side effects that clinicians were seeing that were not particularly noted in the early trials of buprenorphine.

Several of those who attended the workshop said that some of their patients have headaches when they start the medication and some complain of feeling fatigued.

Dr. McNicholas said experience is suggesting that 20% of patients experience head-aches when they first go on buprenorphine, but that the condition always resolves in a few days.

Regarding the fatigue issue, Dr. McNicholas said she was skeptical of those complaints because, kinetically, the drug should not have that effect. However, when pressed by several of those who said that they did have fatigued patients, she allowed: “I am not saying it is not real, but I certainly haven't seen it–and we have no data.

“I hear things, frankly, that we did not see during the studies,” one of which was occurrence of headaches, she added.

There continue to be no worrisome reports of drug-drug interactions with buprenorphine. Such interactions were expected because it is given by sublingual administration; this is done so that large amounts do not assault the liver, but it means that most of the medication goes to the brain first.

SCOTTSDALE, ARIZ. – At a recent workshop on office buprenorphine prescribing, the first question addressed was: Is the 30-patient limit likely to be revised?

The urgency of the question is another sign that physicians who choose to become waiver-qualified to treat patients addicted to narcotics under the Drug Addiction Treatment Act of 2000 continue to find that the demand surpasses their ability to provide care.

Currently, about 5,000 physicians have the waiver to prescribe buprenorphine for addiction treatment, said Dr. Laura F. McNicholas, who led the workshop, which was held at the annual meeting of the American Academy of Addiction Psychiatry. It has been reported that fewer than half that number regularly prescribe, however.

Those who do prescribe tend to be swamped with patients. Many of the specialists who attended the workshop mentioned that they would like to be able to refer patients they have gotten stabilized to create more room on their rosters, but they have been unable to find other physicians to take those patients.

Last year, federal officials relaxed the limit set on the number of patients who could be treated from 30 patients at any one site to 30 patients per waiver-qualified physician. This has led many to question whether further relaxation is forthcoming.

Among those familiar with the machinations of the federal government, the sense is that Congress may be amenable to the idea of loosening the limits further because federal officials are satisfied with the way the program has been working.

But some limits will stay be in place, at least for the time being, said Dr. McNicholas, who recently chaired a panel that developed office buprenorphine guidelines for the Substance Abuse and Mental Health Services Administration.

The medical groups involved have not come to a consensus about the new limits they should seek from Congress, but discussions have begun, she added.

A recent assessment document on the buprenorphine prescribing program shows that even the Drug Enforcement Agency is satisfied with the program, said Dr. McNicholas, of the University of Pennsylvania Treatment Research Center, Philadelphia.

The document, which has been discussed but not yet finalized or published, says that, as expected, the program is reaching a different demographic of narcotics addicts than has traditionally been involved with methadone programs and other kinds of treatment. Those prescribed buprenorphine are more middle class and less likely to be addicted to heroin.

Figures in the report, which covers 3 years, indicate that about 60% of the patients treated through the program had never been in drug treatment before, and about 40% had been abusing diverted prescription medications, such as OxyContin, Dr. McNicholas said.

The report also says that while there has been diversion of buprenorphine, it does not appear to be a major problem. In fact, it notes that many of the cases have involved patients giving the medication to friends, who then find it so efficacious that they seek out treatment for themselves.

Another topic of discussion during the workshop involved the side effects that clinicians were seeing that were not particularly noted in the early trials of buprenorphine.

Several of those who attended the workshop said that some of their patients have headaches when they start the medication and some complain of feeling fatigued.

Dr. McNicholas said experience is suggesting that 20% of patients experience head-aches when they first go on buprenorphine, but that the condition always resolves in a few days.

Regarding the fatigue issue, Dr. McNicholas said she was skeptical of those complaints because, kinetically, the drug should not have that effect. However, when pressed by several of those who said that they did have fatigued patients, she allowed: “I am not saying it is not real, but I certainly haven't seen it–and we have no data.

“I hear things, frankly, that we did not see during the studies,” one of which was occurrence of headaches, she added.

There continue to be no worrisome reports of drug-drug interactions with buprenorphine. Such interactions were expected because it is given by sublingual administration; this is done so that large amounts do not assault the liver, but it means that most of the medication goes to the brain first.

SCOTTSDALE, ARIZ. – At a recent workshop on office buprenorphine prescribing, the first question addressed was: Is the 30-patient limit likely to be revised?

The urgency of the question is another sign that physicians who choose to become waiver-qualified to treat patients addicted to narcotics under the Drug Addiction Treatment Act of 2000 continue to find that the demand surpasses their ability to provide care.

Currently, about 5,000 physicians have the waiver to prescribe buprenorphine for addiction treatment, said Dr. Laura F. McNicholas, who led the workshop, which was held at the annual meeting of the American Academy of Addiction Psychiatry. It has been reported that fewer than half that number regularly prescribe, however.

Those who do prescribe tend to be swamped with patients. Many of the specialists who attended the workshop mentioned that they would like to be able to refer patients they have gotten stabilized to create more room on their rosters, but they have been unable to find other physicians to take those patients.

Last year, federal officials relaxed the limit set on the number of patients who could be treated from 30 patients at any one site to 30 patients per waiver-qualified physician. This has led many to question whether further relaxation is forthcoming.

Among those familiar with the machinations of the federal government, the sense is that Congress may be amenable to the idea of loosening the limits further because federal officials are satisfied with the way the program has been working.

But some limits will stay be in place, at least for the time being, said Dr. McNicholas, who recently chaired a panel that developed office buprenorphine guidelines for the Substance Abuse and Mental Health Services Administration.

The medical groups involved have not come to a consensus about the new limits they should seek from Congress, but discussions have begun, she added.

A recent assessment document on the buprenorphine prescribing program shows that even the Drug Enforcement Agency is satisfied with the program, said Dr. McNicholas, of the University of Pennsylvania Treatment Research Center, Philadelphia.

The document, which has been discussed but not yet finalized or published, says that, as expected, the program is reaching a different demographic of narcotics addicts than has traditionally been involved with methadone programs and other kinds of treatment. Those prescribed buprenorphine are more middle class and less likely to be addicted to heroin.

Figures in the report, which covers 3 years, indicate that about 60% of the patients treated through the program had never been in drug treatment before, and about 40% had been abusing diverted prescription medications, such as OxyContin, Dr. McNicholas said.

The report also says that while there has been diversion of buprenorphine, it does not appear to be a major problem. In fact, it notes that many of the cases have involved patients giving the medication to friends, who then find it so efficacious that they seek out treatment for themselves.

Another topic of discussion during the workshop involved the side effects that clinicians were seeing that were not particularly noted in the early trials of buprenorphine.

Several of those who attended the workshop said that some of their patients have headaches when they start the medication and some complain of feeling fatigued.

Dr. McNicholas said experience is suggesting that 20% of patients experience head-aches when they first go on buprenorphine, but that the condition always resolves in a few days.

Regarding the fatigue issue, Dr. McNicholas said she was skeptical of those complaints because, kinetically, the drug should not have that effect. However, when pressed by several of those who said that they did have fatigued patients, she allowed: “I am not saying it is not real, but I certainly haven't seen it–and we have no data.

“I hear things, frankly, that we did not see during the studies,” one of which was occurrence of headaches, she added.

There continue to be no worrisome reports of drug-drug interactions with buprenorphine. Such interactions were expected because it is given by sublingual administration; this is done so that large amounts do not assault the liver, but it means that most of the medication goes to the brain first.

SAN FRANCISCO — The generalization that the more procedures a hospital does, the better it is, may be an oversimplification at best and misleading at worst, according to two studies presented at the annual clinical congress of the American College of Surgeons.

In one study, Dr. Melissa A. Meyers and her coinvestigators compared colectomy mortality in rural hospitals with that in urban hospitals, using Medicare data on 279,385 patients who had surgery between 1994 and 1999.

Overall mortality was the same in the two groups. In small rural hospitals with a low volume of procedures, the mortality rate was 6.7%. In urban hospitals, most of which had higher volume, the rate was 6.4%, said Dr. Meyers of the surgery department at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Analysis of the data did show some evidence that the more colectomies a hospital performed the lower the mortality, but that held only for the urban hospitals. Rural hospitals had no such correlation between volume and mortality, though 90% of the rural hospitals had a low volume. And mortality at the rural hospitals was not much different from that at the best urban hospitals, where the rate was 5.6%.

“Hospital procedure volume is a poor proxy for quality in a rural setting, and we need to develop better ways to gauge quality in hospitals overall,” Dr. Meyers said.

In the second study, Dr. Dharam Kumbhani and his colleagues looked at 30-day mortality for 10 different surgical procedures in the Veterans Administration system. The study was a repeat of an earlier, highly controversial investigation that the authors decided to revisit with more recent data. Both studies used data from the Veterans Affairs (VA) National Surgical Quality Improvement Program.

The earlier study found no relationship in the VA system between surgical volume and outcome for eight different surgical procedures. The present study, which looked at procedures ranging from carotid endarterectomy and total hip arthroplasty to pancreaticoduodenectomy, again found no relationship between low volume and worse outcome, said Dr. Kumbhani of the VA Boston Healthcare System.

In 8 of the 10 surgical procedures, there was a statistically significant relationship between low volume and the observed-to-expected ratio of 30-day mortality. However, this difference was not clinically significant, Dr. Kumbhani said. Moreover, when the data were analyzed using a hierarchical model that accounted for patient and hospital factors, no relationship was found between volume and 30-day mortality.

“We believe that systems of care are much more important than volume in determining the quality of surgical care,” he said. “A lot of high-volume centers have better risk-adjusted outcomes, not because they have higher volumes but because they have better systems in place.”

The findings of his study are probably more accurate than other studies of volume and surgical outcome, because the VA program collects all of its data prospectively and was designed for just this type of analysis, Dr. Kumbhani added.

Most of those who attended the presentations were gratified by the results. During the animated discussion period, it was suggested that the studies should serve as a cautionary note to efforts to measure quality solely in terms of volume, because the volume-quality equation perhaps only holds for very sophisticated procedures such as transplants.

But Dr. Justin Dimick of the Veterans Affairs Medical Center in White River Junction, Vt., a designated discussant for the VA study, took issue with generalizing its results. The study's findings are at odds with an extensive body of research showing that the more a surgeon or a hospital does a particular procedure the better they are at it, he said.

SAN FRANCISCO — The generalization that the more procedures a hospital does, the better it is, may be an oversimplification at best and misleading at worst, according to two studies presented at the annual clinical congress of the American College of Surgeons.

In one study, Dr. Melissa A. Meyers and her coinvestigators compared colectomy mortality in rural hospitals with that in urban hospitals, using Medicare data on 279,385 patients who had surgery between 1994 and 1999.

Overall mortality was the same in the two groups. In small rural hospitals with a low volume of procedures, the mortality rate was 6.7%. In urban hospitals, most of which had higher volume, the rate was 6.4%, said Dr. Meyers of the surgery department at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Analysis of the data did show some evidence that the more colectomies a hospital performed the lower the mortality, but that held only for the urban hospitals. Rural hospitals had no such correlation between volume and mortality, though 90% of the rural hospitals had a low volume. And mortality at the rural hospitals was not much different from that at the best urban hospitals, where the rate was 5.6%.

“Hospital procedure volume is a poor proxy for quality in a rural setting, and we need to develop better ways to gauge quality in hospitals overall,” Dr. Meyers said.

In the second study, Dr. Dharam Kumbhani and his colleagues looked at 30-day mortality for 10 different surgical procedures in the Veterans Administration system. The study was a repeat of an earlier, highly controversial investigation that the authors decided to revisit with more recent data. Both studies used data from the Veterans Affairs (VA) National Surgical Quality Improvement Program.

The earlier study found no relationship in the VA system between surgical volume and outcome for eight different surgical procedures. The present study, which looked at procedures ranging from carotid endarterectomy and total hip arthroplasty to pancreaticoduodenectomy, again found no relationship between low volume and worse outcome, said Dr. Kumbhani of the VA Boston Healthcare System.

In 8 of the 10 surgical procedures, there was a statistically significant relationship between low volume and the observed-to-expected ratio of 30-day mortality. However, this difference was not clinically significant, Dr. Kumbhani said. Moreover, when the data were analyzed using a hierarchical model that accounted for patient and hospital factors, no relationship was found between volume and 30-day mortality.

“We believe that systems of care are much more important than volume in determining the quality of surgical care,” he said. “A lot of high-volume centers have better risk-adjusted outcomes, not because they have higher volumes but because they have better systems in place.”

The findings of his study are probably more accurate than other studies of volume and surgical outcome, because the VA program collects all of its data prospectively and was designed for just this type of analysis, Dr. Kumbhani added.

Most of those who attended the presentations were gratified by the results. During the animated discussion period, it was suggested that the studies should serve as a cautionary note to efforts to measure quality solely in terms of volume, because the volume-quality equation perhaps only holds for very sophisticated procedures such as transplants.

But Dr. Justin Dimick of the Veterans Affairs Medical Center in White River Junction, Vt., a designated discussant for the VA study, took issue with generalizing its results. The study's findings are at odds with an extensive body of research showing that the more a surgeon or a hospital does a particular procedure the better they are at it, he said.

SAN FRANCISCO — The generalization that the more procedures a hospital does, the better it is, may be an oversimplification at best and misleading at worst, according to two studies presented at the annual clinical congress of the American College of Surgeons.

In one study, Dr. Melissa A. Meyers and her coinvestigators compared colectomy mortality in rural hospitals with that in urban hospitals, using Medicare data on 279,385 patients who had surgery between 1994 and 1999.

Overall mortality was the same in the two groups. In small rural hospitals with a low volume of procedures, the mortality rate was 6.7%. In urban hospitals, most of which had higher volume, the rate was 6.4%, said Dr. Meyers of the surgery department at Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Analysis of the data did show some evidence that the more colectomies a hospital performed the lower the mortality, but that held only for the urban hospitals. Rural hospitals had no such correlation between volume and mortality, though 90% of the rural hospitals had a low volume. And mortality at the rural hospitals was not much different from that at the best urban hospitals, where the rate was 5.6%.

“Hospital procedure volume is a poor proxy for quality in a rural setting, and we need to develop better ways to gauge quality in hospitals overall,” Dr. Meyers said.

In the second study, Dr. Dharam Kumbhani and his colleagues looked at 30-day mortality for 10 different surgical procedures in the Veterans Administration system. The study was a repeat of an earlier, highly controversial investigation that the authors decided to revisit with more recent data. Both studies used data from the Veterans Affairs (VA) National Surgical Quality Improvement Program.

The earlier study found no relationship in the VA system between surgical volume and outcome for eight different surgical procedures. The present study, which looked at procedures ranging from carotid endarterectomy and total hip arthroplasty to pancreaticoduodenectomy, again found no relationship between low volume and worse outcome, said Dr. Kumbhani of the VA Boston Healthcare System.

In 8 of the 10 surgical procedures, there was a statistically significant relationship between low volume and the observed-to-expected ratio of 30-day mortality. However, this difference was not clinically significant, Dr. Kumbhani said. Moreover, when the data were analyzed using a hierarchical model that accounted for patient and hospital factors, no relationship was found between volume and 30-day mortality.

“We believe that systems of care are much more important than volume in determining the quality of surgical care,” he said. “A lot of high-volume centers have better risk-adjusted outcomes, not because they have higher volumes but because they have better systems in place.”

The findings of his study are probably more accurate than other studies of volume and surgical outcome, because the VA program collects all of its data prospectively and was designed for just this type of analysis, Dr. Kumbhani added.

Most of those who attended the presentations were gratified by the results. During the animated discussion period, it was suggested that the studies should serve as a cautionary note to efforts to measure quality solely in terms of volume, because the volume-quality equation perhaps only holds for very sophisticated procedures such as transplants.

But Dr. Justin Dimick of the Veterans Affairs Medical Center in White River Junction, Vt., a designated discussant for the VA study, took issue with generalizing its results. The study's findings are at odds with an extensive body of research showing that the more a surgeon or a hospital does a particular procedure the better they are at it, he said.

SAN FRANCISCO — Bariatric surgery may carry a higher mortality risk than previously reported, according to a study of Medicare patients presented by Dr. David R. Flum at the annual clinical congress of the American College of Surgeons.

Previous reports have suggested that the mortality risk from gastric bypass procedures is only 1%–2%.

In the new study, Dr. Flum and colleagues looked at a Medicare database of 16,000 gastric bypass procedures performed between 1997 and 2002. Patients in the database were mostly female (75%), and the average age of the patients was 47 years, with 90% younger than 65 years. The investigators could not tell if the procedures were open or laparoscopic; however, most were presumed to have been open given the time period.

The analysis showed that the mortality rate was 2.0% at 30 days post procedure, 2.8% at 90 days, and 4.6% at 1 year, said Dr. Flum of the surgery department at the University of Washington, Seattle. Older patients and males had a higher risk of mortality than other patients, a fact that most surgeons who perform obesity procedures are well aware of, he added. The 30-day mortality rate was 3.7% for males versus 1.5% for females, and the mortality risk of patients 65 years or older was 3 times that of patients younger than 65, with a mortality rate of 44% at 1 year among those 75 years or older.

The researchers also calculated patient mortality for the individual surgeons who performed the procedures. That analysis showed a pattern of lower mortality with the surgeons who performed the highest number of Medicare procedures, although it is not known from the data whether that pattern represents better technical skill or more restrictive patient selection by those experienced surgeons, Dr. Flum said.

Among the surgeons who performed the most procedures (more than 71 during the period studied), the 30-day mortality for patients older than 65 years (1.8%) was about the same as it was for younger patients (1.1%).

Dr. Flum noted that Medicare patients are either over 65 years of age or disabled, and therefore probably do not reflect the general population of patients who undergo bariatric surgery.

Moreover, the study does not indicate what the mortality would have been in this population had they not undergone surgery.

Still, the study provides important information, particularly now with the number of procedures continuing to grow, Dr. Flum said.

“Trying to make it look like bariatric surgery has zero deaths, which has been an approach used by many advocates for a decade, is problematic,” he said. “This helps set the bar more realistically.”

“If we don't use this data to help start an enlightened conversation about how to apply bariatric surgery, we're really missing a tremendous opportunity,” he added.

SAN FRANCISCO — Bariatric surgery may carry a higher mortality risk than previously reported, according to a study of Medicare patients presented by Dr. David R. Flum at the annual clinical congress of the American College of Surgeons.

Previous reports have suggested that the mortality risk from gastric bypass procedures is only 1%–2%.

In the new study, Dr. Flum and colleagues looked at a Medicare database of 16,000 gastric bypass procedures performed between 1997 and 2002. Patients in the database were mostly female (75%), and the average age of the patients was 47 years, with 90% younger than 65 years. The investigators could not tell if the procedures were open or laparoscopic; however, most were presumed to have been open given the time period.

The analysis showed that the mortality rate was 2.0% at 30 days post procedure, 2.8% at 90 days, and 4.6% at 1 year, said Dr. Flum of the surgery department at the University of Washington, Seattle. Older patients and males had a higher risk of mortality than other patients, a fact that most surgeons who perform obesity procedures are well aware of, he added. The 30-day mortality rate was 3.7% for males versus 1.5% for females, and the mortality risk of patients 65 years or older was 3 times that of patients younger than 65, with a mortality rate of 44% at 1 year among those 75 years or older.

The researchers also calculated patient mortality for the individual surgeons who performed the procedures. That analysis showed a pattern of lower mortality with the surgeons who performed the highest number of Medicare procedures, although it is not known from the data whether that pattern represents better technical skill or more restrictive patient selection by those experienced surgeons, Dr. Flum said.

Among the surgeons who performed the most procedures (more than 71 during the period studied), the 30-day mortality for patients older than 65 years (1.8%) was about the same as it was for younger patients (1.1%).

Dr. Flum noted that Medicare patients are either over 65 years of age or disabled, and therefore probably do not reflect the general population of patients who undergo bariatric surgery.

Moreover, the study does not indicate what the mortality would have been in this population had they not undergone surgery.

Still, the study provides important information, particularly now with the number of procedures continuing to grow, Dr. Flum said.

“Trying to make it look like bariatric surgery has zero deaths, which has been an approach used by many advocates for a decade, is problematic,” he said. “This helps set the bar more realistically.”

“If we don't use this data to help start an enlightened conversation about how to apply bariatric surgery, we're really missing a tremendous opportunity,” he added.

SAN FRANCISCO — Bariatric surgery may carry a higher mortality risk than previously reported, according to a study of Medicare patients presented by Dr. David R. Flum at the annual clinical congress of the American College of Surgeons.

Previous reports have suggested that the mortality risk from gastric bypass procedures is only 1%–2%.

In the new study, Dr. Flum and colleagues looked at a Medicare database of 16,000 gastric bypass procedures performed between 1997 and 2002. Patients in the database were mostly female (75%), and the average age of the patients was 47 years, with 90% younger than 65 years. The investigators could not tell if the procedures were open or laparoscopic; however, most were presumed to have been open given the time period.

The analysis showed that the mortality rate was 2.0% at 30 days post procedure, 2.8% at 90 days, and 4.6% at 1 year, said Dr. Flum of the surgery department at the University of Washington, Seattle. Older patients and males had a higher risk of mortality than other patients, a fact that most surgeons who perform obesity procedures are well aware of, he added. The 30-day mortality rate was 3.7% for males versus 1.5% for females, and the mortality risk of patients 65 years or older was 3 times that of patients younger than 65, with a mortality rate of 44% at 1 year among those 75 years or older.

The researchers also calculated patient mortality for the individual surgeons who performed the procedures. That analysis showed a pattern of lower mortality with the surgeons who performed the highest number of Medicare procedures, although it is not known from the data whether that pattern represents better technical skill or more restrictive patient selection by those experienced surgeons, Dr. Flum said.

Among the surgeons who performed the most procedures (more than 71 during the period studied), the 30-day mortality for patients older than 65 years (1.8%) was about the same as it was for younger patients (1.1%).

Dr. Flum noted that Medicare patients are either over 65 years of age or disabled, and therefore probably do not reflect the general population of patients who undergo bariatric surgery.

Moreover, the study does not indicate what the mortality would have been in this population had they not undergone surgery.

Still, the study provides important information, particularly now with the number of procedures continuing to grow, Dr. Flum said.

“Trying to make it look like bariatric surgery has zero deaths, which has been an approach used by many advocates for a decade, is problematic,” he said. “This helps set the bar more realistically.”

“If we don't use this data to help start an enlightened conversation about how to apply bariatric surgery, we're really missing a tremendous opportunity,” he added.

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups (28.76 ng/mL for the osteoarthritis group vs. 29.16 for the fibromyalgia group) even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% vs. 20%.

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups (28.76 ng/mL for the osteoarthritis group vs. 29.16 for the fibromyalgia group) even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% vs. 20%.

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant.

Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups (28.76 ng/mL for the osteoarthritis group vs. 29.16 for the fibromyalgia group) even though there was a slightly higher percentage of patients with fibromyalgia who were insufficient, 29% vs. 20%.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation.

Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group.

None of the patients on placebo had a reduction below 6 mg/dL in their last three measurements.

Dr. Schumacher noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Of the subjects on 240 mg a day of febuxostat, 75% got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, he added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, he added. Dr. Schumacher received funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation.

Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group.

None of the patients on placebo had a reduction below 6 mg/dL in their last three measurements.

Dr. Schumacher noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Of the subjects on 240 mg a day of febuxostat, 75% got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, he added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, he added. Dr. Schumacher received funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation.

Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group.

None of the patients on placebo had a reduction below 6 mg/dL in their last three measurements.

Dr. Schumacher noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Of the subjects on 240 mg a day of febuxostat, 75% got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, he added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, he added. Dr. Schumacher received funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SAN DIEGO — Wedged shoe insoles may do little for medial knee osteoarthritic pain, according to a small, 18-week trial presented at the annual meeting of the American College of Rheumatology.

“A 5-degree lateral wedged insole was not efficacious in people with medial knee osteoarthritis in this particular trial,” said Kristin Baker, Ph.D., of the clinical epidemiology research and training unit at Boston University.

The randomized, double-blind, crossover trial, which enrolled 46 individuals with radiographically confirmed medial knee osteoarthritis, was designed to detect a 10% treatment effect on the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The wedged insole did not have this effect.

Given the patients' baseline WOMAC pain scores (a mean of 266 on the 0- to 500-point scale), a positive treatment effect would have been a decrease of 26–27 points. The study found that the wedge produced a mean 13-point benefit.

Use of a wedged insole did not result in the participants' being able to take less pain medication.

In a subgroup analysis, individuals with a body mass index (kg/m

The study began with a 2-week washout period, during which participants kept a pain diary. During the subsequent 6 weeks, subjects wore either a 5-degree lateral-wedge insole or a neutral insole. Then, for 4 more weeks, they did not wear any insole. For the final 6 weeks, participants crossed over and wore the other type of insole.

Patients were expected to wear the insoles for at least 8 hours per day, and their compliance rate was high, Dr. Baker said.

SAN DIEGO — Wedged shoe insoles may do little for medial knee osteoarthritic pain, according to a small, 18-week trial presented at the annual meeting of the American College of Rheumatology.

“A 5-degree lateral wedged insole was not efficacious in people with medial knee osteoarthritis in this particular trial,” said Kristin Baker, Ph.D., of the clinical epidemiology research and training unit at Boston University.

The randomized, double-blind, crossover trial, which enrolled 46 individuals with radiographically confirmed medial knee osteoarthritis, was designed to detect a 10% treatment effect on the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The wedged insole did not have this effect.

Given the patients' baseline WOMAC pain scores (a mean of 266 on the 0- to 500-point scale), a positive treatment effect would have been a decrease of 26–27 points. The study found that the wedge produced a mean 13-point benefit.

Use of a wedged insole did not result in the participants' being able to take less pain medication.

In a subgroup analysis, individuals with a body mass index (kg/m

The study began with a 2-week washout period, during which participants kept a pain diary. During the subsequent 6 weeks, subjects wore either a 5-degree lateral-wedge insole or a neutral insole. Then, for 4 more weeks, they did not wear any insole. For the final 6 weeks, participants crossed over and wore the other type of insole.

Patients were expected to wear the insoles for at least 8 hours per day, and their compliance rate was high, Dr. Baker said.

SAN DIEGO — Wedged shoe insoles may do little for medial knee osteoarthritic pain, according to a small, 18-week trial presented at the annual meeting of the American College of Rheumatology.

“A 5-degree lateral wedged insole was not efficacious in people with medial knee osteoarthritis in this particular trial,” said Kristin Baker, Ph.D., of the clinical epidemiology research and training unit at Boston University.

The randomized, double-blind, crossover trial, which enrolled 46 individuals with radiographically confirmed medial knee osteoarthritis, was designed to detect a 10% treatment effect on the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The wedged insole did not have this effect.

Given the patients' baseline WOMAC pain scores (a mean of 266 on the 0- to 500-point scale), a positive treatment effect would have been a decrease of 26–27 points. The study found that the wedge produced a mean 13-point benefit.

Use of a wedged insole did not result in the participants' being able to take less pain medication.

In a subgroup analysis, individuals with a body mass index (kg/m

The study began with a 2-week washout period, during which participants kept a pain diary. During the subsequent 6 weeks, subjects wore either a 5-degree lateral-wedge insole or a neutral insole. Then, for 4 more weeks, they did not wear any insole. For the final 6 weeks, participants crossed over and wore the other type of insole.

Patients were expected to wear the insoles for at least 8 hours per day, and their compliance rate was high, Dr. Baker said.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.