Rheumatoid Arthritis

AMSTERDAM — The clinical response to repeat courses of rituximab equalled or surpassed the initial course in patients with rheumatoid arthritis who are participating in a long-term open-label study, Dr. Paul Emery said at the annual European Congress of Rheumatology.

Patients with rheumatoid arthritis (RA) unresponsive to traditional disease-modifying antirheumatic drugs but who achieved at least a 20% improvement in tender and swollen joint counts following a single course of rituximab were eligible to receive additional courses for residual disease.

To date, 145 patients have received at least two courses, and 24-week follow-up data are available for 99. Each treatment course consists of two separate infusions, 1,000 mg each, 2 weeks apart.

Baseline characteristics of the 99 patients were similar to those of the original larger study population, where the mean age was 54 years and disease duration was 10 years.

Mean tender and swollen joint counts at baseline were approximately 32 and 20, respectively, and mean disease activity score including a 28-joint count (DAS28) was 6.8 (N. Engl. J. Med. 2004; 350:2572–81).

A total of 58 (59%) of patients had achieved an ACR20 response 24 weeks after the first course of rituximab, while 72 (73%) reached this level of response 24 weeks after the second course, according to Dr. Emery, professor of rheumatology and clinical director of the Academic Unit of Musculoskeletal Disease at the Leeds (England) Teaching Hospitals Trust.

Maximal efficacy with rituximab generally is seen at 24 weeks.

Increased efficacy also was apparent on other measures. (See table.)

Repeat courses of the B-cell-depleting agent were well tolerated, and there was no evidence of increased overall incidence of adverse events, numbers of infections, or infusion reactions, he said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — The clinical response to repeat courses of rituximab equalled or surpassed the initial course in patients with rheumatoid arthritis who are participating in a long-term open-label study, Dr. Paul Emery said at the annual European Congress of Rheumatology.

Patients with rheumatoid arthritis (RA) unresponsive to traditional disease-modifying antirheumatic drugs but who achieved at least a 20% improvement in tender and swollen joint counts following a single course of rituximab were eligible to receive additional courses for residual disease.

To date, 145 patients have received at least two courses, and 24-week follow-up data are available for 99. Each treatment course consists of two separate infusions, 1,000 mg each, 2 weeks apart.

Baseline characteristics of the 99 patients were similar to those of the original larger study population, where the mean age was 54 years and disease duration was 10 years.

Mean tender and swollen joint counts at baseline were approximately 32 and 20, respectively, and mean disease activity score including a 28-joint count (DAS28) was 6.8 (N. Engl. J. Med. 2004; 350:2572–81).

A total of 58 (59%) of patients had achieved an ACR20 response 24 weeks after the first course of rituximab, while 72 (73%) reached this level of response 24 weeks after the second course, according to Dr. Emery, professor of rheumatology and clinical director of the Academic Unit of Musculoskeletal Disease at the Leeds (England) Teaching Hospitals Trust.

Maximal efficacy with rituximab generally is seen at 24 weeks.

Increased efficacy also was apparent on other measures. (See table.)

Repeat courses of the B-cell-depleting agent were well tolerated, and there was no evidence of increased overall incidence of adverse events, numbers of infections, or infusion reactions, he said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — The clinical response to repeat courses of rituximab equalled or surpassed the initial course in patients with rheumatoid arthritis who are participating in a long-term open-label study, Dr. Paul Emery said at the annual European Congress of Rheumatology.

Patients with rheumatoid arthritis (RA) unresponsive to traditional disease-modifying antirheumatic drugs but who achieved at least a 20% improvement in tender and swollen joint counts following a single course of rituximab were eligible to receive additional courses for residual disease.

To date, 145 patients have received at least two courses, and 24-week follow-up data are available for 99. Each treatment course consists of two separate infusions, 1,000 mg each, 2 weeks apart.

Baseline characteristics of the 99 patients were similar to those of the original larger study population, where the mean age was 54 years and disease duration was 10 years.

Mean tender and swollen joint counts at baseline were approximately 32 and 20, respectively, and mean disease activity score including a 28-joint count (DAS28) was 6.8 (N. Engl. J. Med. 2004; 350:2572–81).

A total of 58 (59%) of patients had achieved an ACR20 response 24 weeks after the first course of rituximab, while 72 (73%) reached this level of response 24 weeks after the second course, according to Dr. Emery, professor of rheumatology and clinical director of the Academic Unit of Musculoskeletal Disease at the Leeds (England) Teaching Hospitals Trust.

Maximal efficacy with rituximab generally is seen at 24 weeks.

Increased efficacy also was apparent on other measures. (See table.)

Repeat courses of the B-cell-depleting agent were well tolerated, and there was no evidence of increased overall incidence of adverse events, numbers of infections, or infusion reactions, he said.

ELSEVIER GLOBAL MEDICAL NEWS

GLASGOW, SCOTLAND — Successful stem cell transplantation in two patients with recalcitrant Still's disease suggests that this approach could offer a viable alternative for patients who do not respond to other therapies, according to Dr. Hanumantha V. Reddy.

Treatment typically includes nonsteroidal anti-inflammatory drugs, high-dose corticosteroids, and intravenous immunoglobulin. Disease-modifying antirheumatic drugs (DMARDs) are sometimes used, although they tend to be more beneficial for the articular symptoms than for the systemic abnormalities, noted Dr. Reddy in a poster session at the annual meeting of the British Society for Rheumatology.

In the first case, explained by Dr. Reddy, a 34-year-old woman had intermittent fever, rash, arthritis that was significantly erosive, leukocytosis, anemia, and elevated inflammatory markers. She was steroid dependent and had not responded to DMARDs or biologic therapies.

She underwent autologous stem cell transplantation in early 2003 and responded well, soon entering remission with normalization of her inflammatory markers. In 2004, she had a successful pregnancy, and she remains in remission, Dr. Reddy reported.

The second stem cell transplantation involved a 24-year-old woman who had been diagnosed with Still's disease at age 14 and had frequent flares but no significant joint damage. She too was steroid dependent and had not responded to traditional DMARDs, biologic therapies, or intravenous immunoglobulin, according to Dr. Reddy of the rheumatology department, Royal Liverpool University Hospital, England.

The patient underwent autologous stem cell transplantation. The posttransplant period was complicated by 3 months of persistent fever, presumed to be viral in origin. She also experienced two episodes of severe autoimmune hemolysis characterized by frank hematuria and the presence of Kidd group antibodies. She recovered well, however, and is currently in remission, Dr. Reddy reported.

Stem cell transplantation risks were seen in a series of 34 children with juvenile idiopathic arthritis who underwent the procedure. Although 53% of patients in this series responded well and experienced drug-free remission, five died—two from disease relapse and three from infection-associated hemophagocytic syndrome (Ann. Rheum. Dis. 2004;63:1318–26).

GLASGOW, SCOTLAND — Successful stem cell transplantation in two patients with recalcitrant Still's disease suggests that this approach could offer a viable alternative for patients who do not respond to other therapies, according to Dr. Hanumantha V. Reddy.

Treatment typically includes nonsteroidal anti-inflammatory drugs, high-dose corticosteroids, and intravenous immunoglobulin. Disease-modifying antirheumatic drugs (DMARDs) are sometimes used, although they tend to be more beneficial for the articular symptoms than for the systemic abnormalities, noted Dr. Reddy in a poster session at the annual meeting of the British Society for Rheumatology.

In the first case, explained by Dr. Reddy, a 34-year-old woman had intermittent fever, rash, arthritis that was significantly erosive, leukocytosis, anemia, and elevated inflammatory markers. She was steroid dependent and had not responded to DMARDs or biologic therapies.

She underwent autologous stem cell transplantation in early 2003 and responded well, soon entering remission with normalization of her inflammatory markers. In 2004, she had a successful pregnancy, and she remains in remission, Dr. Reddy reported.

The second stem cell transplantation involved a 24-year-old woman who had been diagnosed with Still's disease at age 14 and had frequent flares but no significant joint damage. She too was steroid dependent and had not responded to traditional DMARDs, biologic therapies, or intravenous immunoglobulin, according to Dr. Reddy of the rheumatology department, Royal Liverpool University Hospital, England.

The patient underwent autologous stem cell transplantation. The posttransplant period was complicated by 3 months of persistent fever, presumed to be viral in origin. She also experienced two episodes of severe autoimmune hemolysis characterized by frank hematuria and the presence of Kidd group antibodies. She recovered well, however, and is currently in remission, Dr. Reddy reported.

Stem cell transplantation risks were seen in a series of 34 children with juvenile idiopathic arthritis who underwent the procedure. Although 53% of patients in this series responded well and experienced drug-free remission, five died—two from disease relapse and three from infection-associated hemophagocytic syndrome (Ann. Rheum. Dis. 2004;63:1318–26).

GLASGOW, SCOTLAND — Successful stem cell transplantation in two patients with recalcitrant Still's disease suggests that this approach could offer a viable alternative for patients who do not respond to other therapies, according to Dr. Hanumantha V. Reddy.

Treatment typically includes nonsteroidal anti-inflammatory drugs, high-dose corticosteroids, and intravenous immunoglobulin. Disease-modifying antirheumatic drugs (DMARDs) are sometimes used, although they tend to be more beneficial for the articular symptoms than for the systemic abnormalities, noted Dr. Reddy in a poster session at the annual meeting of the British Society for Rheumatology.

In the first case, explained by Dr. Reddy, a 34-year-old woman had intermittent fever, rash, arthritis that was significantly erosive, leukocytosis, anemia, and elevated inflammatory markers. She was steroid dependent and had not responded to DMARDs or biologic therapies.

She underwent autologous stem cell transplantation in early 2003 and responded well, soon entering remission with normalization of her inflammatory markers. In 2004, she had a successful pregnancy, and she remains in remission, Dr. Reddy reported.

The second stem cell transplantation involved a 24-year-old woman who had been diagnosed with Still's disease at age 14 and had frequent flares but no significant joint damage. She too was steroid dependent and had not responded to traditional DMARDs, biologic therapies, or intravenous immunoglobulin, according to Dr. Reddy of the rheumatology department, Royal Liverpool University Hospital, England.

The patient underwent autologous stem cell transplantation. The posttransplant period was complicated by 3 months of persistent fever, presumed to be viral in origin. She also experienced two episodes of severe autoimmune hemolysis characterized by frank hematuria and the presence of Kidd group antibodies. She recovered well, however, and is currently in remission, Dr. Reddy reported.

Stem cell transplantation risks were seen in a series of 34 children with juvenile idiopathic arthritis who underwent the procedure. Although 53% of patients in this series responded well and experienced drug-free remission, five died—two from disease relapse and three from infection-associated hemophagocytic syndrome (Ann. Rheum. Dis. 2004;63:1318–26).

AMSTERDAM — Early and aggressive therapy with infliximab and methotrexate may favorably alter the course of rheumatoid arthritis, according to new data from the Dutch BEST trial.

After 3 years of follow-up, 55% of the 120 BEST participants initially randomized to combined therapy with infliximab and methotrexate were able to wean off infliximab. They had discontinued infliximab a median of 26 weeks earlier, thereafter consistently maintaining a Disease Activity Score (DAS) of 2.4 or less, down from a mean baseline DAS of 4.3, Dr. Arie E. van der Bijl reported at the annual European Congress of Rheumatology.

After discontinuing infliximab, most of these patients remained on methotrexate maintenance monotherapy. Of particular note was the finding that 17 patients, or 14% of the original 120, were in clinical remission as defined by a DAS of 1.6 or less without any antirheumatic drugs.

BEST is a multicenter randomized trial comparing four different treatment strategies in 506 patients with early rheumatoid arthritis (RA). Although several audience members speculated that similarly favorable 3-year results might have been achieved with early methotrexate monotherapy, which is known to produce very good outcomes in a minority of RA patients, Dr. van der Bijl of Leiden University Medical Center, the Netherlands, was quick to correct them. Another of the four BEST study arms featured exactly that strategy, and the results in terms of rates of low disease activity or clinical remission weren't nearly as good as in the combined infliximab/methotrexate arm.

The new BEST results warrant cautious interpretation. Whether early infliximab plus methotrexate alters the course of RA must await longer-term follow-up, including radiologic evidence of prevention of progressive joint damage, he stressed.

BEST is supported by the Dutch government and the Dutch College of Health Insurance Companies.

AMSTERDAM — Early and aggressive therapy with infliximab and methotrexate may favorably alter the course of rheumatoid arthritis, according to new data from the Dutch BEST trial.

After 3 years of follow-up, 55% of the 120 BEST participants initially randomized to combined therapy with infliximab and methotrexate were able to wean off infliximab. They had discontinued infliximab a median of 26 weeks earlier, thereafter consistently maintaining a Disease Activity Score (DAS) of 2.4 or less, down from a mean baseline DAS of 4.3, Dr. Arie E. van der Bijl reported at the annual European Congress of Rheumatology.

After discontinuing infliximab, most of these patients remained on methotrexate maintenance monotherapy. Of particular note was the finding that 17 patients, or 14% of the original 120, were in clinical remission as defined by a DAS of 1.6 or less without any antirheumatic drugs.

BEST is a multicenter randomized trial comparing four different treatment strategies in 506 patients with early rheumatoid arthritis (RA). Although several audience members speculated that similarly favorable 3-year results might have been achieved with early methotrexate monotherapy, which is known to produce very good outcomes in a minority of RA patients, Dr. van der Bijl of Leiden University Medical Center, the Netherlands, was quick to correct them. Another of the four BEST study arms featured exactly that strategy, and the results in terms of rates of low disease activity or clinical remission weren't nearly as good as in the combined infliximab/methotrexate arm.

The new BEST results warrant cautious interpretation. Whether early infliximab plus methotrexate alters the course of RA must await longer-term follow-up, including radiologic evidence of prevention of progressive joint damage, he stressed.

BEST is supported by the Dutch government and the Dutch College of Health Insurance Companies.

AMSTERDAM — Early and aggressive therapy with infliximab and methotrexate may favorably alter the course of rheumatoid arthritis, according to new data from the Dutch BEST trial.

After 3 years of follow-up, 55% of the 120 BEST participants initially randomized to combined therapy with infliximab and methotrexate were able to wean off infliximab. They had discontinued infliximab a median of 26 weeks earlier, thereafter consistently maintaining a Disease Activity Score (DAS) of 2.4 or less, down from a mean baseline DAS of 4.3, Dr. Arie E. van der Bijl reported at the annual European Congress of Rheumatology.

After discontinuing infliximab, most of these patients remained on methotrexate maintenance monotherapy. Of particular note was the finding that 17 patients, or 14% of the original 120, were in clinical remission as defined by a DAS of 1.6 or less without any antirheumatic drugs.

BEST is a multicenter randomized trial comparing four different treatment strategies in 506 patients with early rheumatoid arthritis (RA). Although several audience members speculated that similarly favorable 3-year results might have been achieved with early methotrexate monotherapy, which is known to produce very good outcomes in a minority of RA patients, Dr. van der Bijl of Leiden University Medical Center, the Netherlands, was quick to correct them. Another of the four BEST study arms featured exactly that strategy, and the results in terms of rates of low disease activity or clinical remission weren't nearly as good as in the combined infliximab/methotrexate arm.

The new BEST results warrant cautious interpretation. Whether early infliximab plus methotrexate alters the course of RA must await longer-term follow-up, including radiologic evidence of prevention of progressive joint damage, he stressed.

BEST is supported by the Dutch government and the Dutch College of Health Insurance Companies.

The National Guideline Clearinghouse Web site presents clinical practice guidelines with standardized abstracts and tables that allow physicians to make comparison of practice guidelines on similar topics. The clearinghouse was created by the Agency for Healthcare Research and Quality in partnership with the American Medical Association and the America's Health Insurance Plans. For more information, visit www.guideline.gov

The National Guideline Clearinghouse Web site presents clinical practice guidelines with standardized abstracts and tables that allow physicians to make comparison of practice guidelines on similar topics. The clearinghouse was created by the Agency for Healthcare Research and Quality in partnership with the American Medical Association and the America's Health Insurance Plans. For more information, visit www.guideline.gov

The National Guideline Clearinghouse Web site presents clinical practice guidelines with standardized abstracts and tables that allow physicians to make comparison of practice guidelines on similar topics. The clearinghouse was created by the Agency for Healthcare Research and Quality in partnership with the American Medical Association and the America's Health Insurance Plans. For more information, visit www.guideline.gov

AMSTERDAM — Rheumatoid arthritis patients on a tumor necrosis factor antagonist in clinical practice have an increased rate of hospitalization for serious, non-TB infections, but that risk appears to be considerably less than previously reported, Dr. Lars Klareskog said at the annual European Congress of Rheumatology.

Moreover, the Swedish national clinical experience indicates that the rate of hospitalization for serious infections doesn't escalate with increasing time spent on the tumor necrosis factor (TNF) inhibitor. The risk is greatest during the first year; thereafter, it drops off and remains fairly static, according to Dr. Klareskog, professor of rheumatology at the Karolinska Institute, Stockholm.

He presented data from the Swedish Biologics Register, a national population-based registry of all patients on a TNF inhibitor for rheumatoid arthritis (RA). The analysis included 2,465 patients given a TNF inhibitor during 1999–2003. The comparison group consisted of 35,450 Swedish RA patients not treated with an anti-TNF agent; this group included historical controls treated for RA as early as 1964.

It's widely recognized that anti-TNF therapy increases the risk of TB. But that risk remains small, on the order of 0.1 case per 100 person-years on the drug.

Of much greater practical concern is the potential for increased risk of other, more common serious infections. That risk has not been well defined. Some relatively small observational studies have quoted a twofold elevation in risk, while others have found no increase.

A recent metaanalysis of randomized clinical trials reported a twofold increased risk of serious infection in RA patients on TNF inhibitors (JAMA 2006;295:2275–85). However, those trials were of relatively short duration and included a narrow spectrum of patients.

The new analysis of Swedish registry data was designed to help clarify the picture using a large real-world patient experience, Dr. Klareskog said at the meeting, which was sponsored by the European League Against Rheumatism.

With 253 hospitalizations for infection in Swedish patients during 4,471 person-years of therapy with their first TNF inhibitor, the crude rate of infection was 5.7 per 100 person-years, compared with 5.3 per 100 person-years in patients not treated with a TNF antagonist. After adjustment for sex, age, comorbidities, and propensity for hospitalization, patients on their first TNF inhibitor had a significant 28% increased relative risk of hospitalization for serious infection, compared with RA patients who had never taken a TNF antagonist.

In the smaller group of 528 patients on their second TNF inhibitor because their first was ineffective or poorly tolerated, the hospitalization rate for infection was 7.1 per 100 person-years. This represented an adjusted 64% increase in relative risk over that of RA patients who never received a TNF antagonist.

No particular type of infection predominated; the risks of hospitalization for skin, articular, bloodstream, and other infection sites were similarly increased in users of TNF antagonists. The data revealed no big surprises. These data fill out the picture of the risks associated with these agents in real-world practice.

AMSTERDAM — Rheumatoid arthritis patients on a tumor necrosis factor antagonist in clinical practice have an increased rate of hospitalization for serious, non-TB infections, but that risk appears to be considerably less than previously reported, Dr. Lars Klareskog said at the annual European Congress of Rheumatology.

Moreover, the Swedish national clinical experience indicates that the rate of hospitalization for serious infections doesn't escalate with increasing time spent on the tumor necrosis factor (TNF) inhibitor. The risk is greatest during the first year; thereafter, it drops off and remains fairly static, according to Dr. Klareskog, professor of rheumatology at the Karolinska Institute, Stockholm.

He presented data from the Swedish Biologics Register, a national population-based registry of all patients on a TNF inhibitor for rheumatoid arthritis (RA). The analysis included 2,465 patients given a TNF inhibitor during 1999–2003. The comparison group consisted of 35,450 Swedish RA patients not treated with an anti-TNF agent; this group included historical controls treated for RA as early as 1964.

It's widely recognized that anti-TNF therapy increases the risk of TB. But that risk remains small, on the order of 0.1 case per 100 person-years on the drug.

Of much greater practical concern is the potential for increased risk of other, more common serious infections. That risk has not been well defined. Some relatively small observational studies have quoted a twofold elevation in risk, while others have found no increase.

A recent metaanalysis of randomized clinical trials reported a twofold increased risk of serious infection in RA patients on TNF inhibitors (JAMA 2006;295:2275–85). However, those trials were of relatively short duration and included a narrow spectrum of patients.

The new analysis of Swedish registry data was designed to help clarify the picture using a large real-world patient experience, Dr. Klareskog said at the meeting, which was sponsored by the European League Against Rheumatism.

With 253 hospitalizations for infection in Swedish patients during 4,471 person-years of therapy with their first TNF inhibitor, the crude rate of infection was 5.7 per 100 person-years, compared with 5.3 per 100 person-years in patients not treated with a TNF antagonist. After adjustment for sex, age, comorbidities, and propensity for hospitalization, patients on their first TNF inhibitor had a significant 28% increased relative risk of hospitalization for serious infection, compared with RA patients who had never taken a TNF antagonist.

In the smaller group of 528 patients on their second TNF inhibitor because their first was ineffective or poorly tolerated, the hospitalization rate for infection was 7.1 per 100 person-years. This represented an adjusted 64% increase in relative risk over that of RA patients who never received a TNF antagonist.

No particular type of infection predominated; the risks of hospitalization for skin, articular, bloodstream, and other infection sites were similarly increased in users of TNF antagonists. The data revealed no big surprises. These data fill out the picture of the risks associated with these agents in real-world practice.

AMSTERDAM — Rheumatoid arthritis patients on a tumor necrosis factor antagonist in clinical practice have an increased rate of hospitalization for serious, non-TB infections, but that risk appears to be considerably less than previously reported, Dr. Lars Klareskog said at the annual European Congress of Rheumatology.

Moreover, the Swedish national clinical experience indicates that the rate of hospitalization for serious infections doesn't escalate with increasing time spent on the tumor necrosis factor (TNF) inhibitor. The risk is greatest during the first year; thereafter, it drops off and remains fairly static, according to Dr. Klareskog, professor of rheumatology at the Karolinska Institute, Stockholm.

He presented data from the Swedish Biologics Register, a national population-based registry of all patients on a TNF inhibitor for rheumatoid arthritis (RA). The analysis included 2,465 patients given a TNF inhibitor during 1999–2003. The comparison group consisted of 35,450 Swedish RA patients not treated with an anti-TNF agent; this group included historical controls treated for RA as early as 1964.

It's widely recognized that anti-TNF therapy increases the risk of TB. But that risk remains small, on the order of 0.1 case per 100 person-years on the drug.

Of much greater practical concern is the potential for increased risk of other, more common serious infections. That risk has not been well defined. Some relatively small observational studies have quoted a twofold elevation in risk, while others have found no increase.

A recent metaanalysis of randomized clinical trials reported a twofold increased risk of serious infection in RA patients on TNF inhibitors (JAMA 2006;295:2275–85). However, those trials were of relatively short duration and included a narrow spectrum of patients.

The new analysis of Swedish registry data was designed to help clarify the picture using a large real-world patient experience, Dr. Klareskog said at the meeting, which was sponsored by the European League Against Rheumatism.

With 253 hospitalizations for infection in Swedish patients during 4,471 person-years of therapy with their first TNF inhibitor, the crude rate of infection was 5.7 per 100 person-years, compared with 5.3 per 100 person-years in patients not treated with a TNF antagonist. After adjustment for sex, age, comorbidities, and propensity for hospitalization, patients on their first TNF inhibitor had a significant 28% increased relative risk of hospitalization for serious infection, compared with RA patients who had never taken a TNF antagonist.

In the smaller group of 528 patients on their second TNF inhibitor because their first was ineffective or poorly tolerated, the hospitalization rate for infection was 7.1 per 100 person-years. This represented an adjusted 64% increase in relative risk over that of RA patients who never received a TNF antagonist.

No particular type of infection predominated; the risks of hospitalization for skin, articular, bloodstream, and other infection sites were similarly increased in users of TNF antagonists. The data revealed no big surprises. These data fill out the picture of the risks associated with these agents in real-world practice.

AMSTERDAM — Extended-release acetaminophen is a possible alternative to cyclooxygenase-2 inhibitors for pain associated with knee osteoarthritis, Dr. Thomas J. Schnitzer reported at the annual European Congress of Rheumatology.

Current osteoarthritis (OA) guidelines recommend the original shorter-acting formulation of acetaminophen at 4 g/day as a first-line treatment for pain associated with the disease. The extended-release formulation, which is commercially available, offers the advantage of less frequent dosing, explained Dr. Schnitzer, professor of medicine at Northwestern University, Chicago.

He reported on 403 adults with knee OA who participated in a 4-week, 23-center, double-blind U.S. clinical trial. Participants were randomized to extended-release acetaminophen at the recommended adult dosage of 1,300 mg t.i.d., rofecoxib at 12.5 mg/day, or rofecoxib at 25 mg/day.

The mean 143.5-mm drop on the 0- to 500-mm visual analog scale in the acetaminophen group was not significantly different from the results with rofecoxib at 12.5 mg/day, but it was inferior to the 175.9-mm drop with high-dose rofecoxib.

Study withdrawal rates for lack of efficacy were 1.5% with extended-release acetaminophen and 3.6% and 1.6%, respectively, for low- and high-dose rofecoxib. Dropout due to adverse events occurred in 5.9% of the acetaminophen group, 6.5% with rofecoxib 12.5 mg, and 7.0% with 25 mg. Headache was reported by 6.6% of patients on extended-release acetaminophen, compared with 0.7% on the low dose and 5.4% on the high dose of rofecoxib, Dr. Schnitzer noted. Two patients had an acute MI during the 4-week study, both in the rofecoxib 12.5-mg arm. Investigators deemed the MIs unrelated to the study medication.

The study was sponsored by McNeil Consumer Healthcare.

AMSTERDAM — Extended-release acetaminophen is a possible alternative to cyclooxygenase-2 inhibitors for pain associated with knee osteoarthritis, Dr. Thomas J. Schnitzer reported at the annual European Congress of Rheumatology.

Current osteoarthritis (OA) guidelines recommend the original shorter-acting formulation of acetaminophen at 4 g/day as a first-line treatment for pain associated with the disease. The extended-release formulation, which is commercially available, offers the advantage of less frequent dosing, explained Dr. Schnitzer, professor of medicine at Northwestern University, Chicago.

He reported on 403 adults with knee OA who participated in a 4-week, 23-center, double-blind U.S. clinical trial. Participants were randomized to extended-release acetaminophen at the recommended adult dosage of 1,300 mg t.i.d., rofecoxib at 12.5 mg/day, or rofecoxib at 25 mg/day.

The mean 143.5-mm drop on the 0- to 500-mm visual analog scale in the acetaminophen group was not significantly different from the results with rofecoxib at 12.5 mg/day, but it was inferior to the 175.9-mm drop with high-dose rofecoxib.

Study withdrawal rates for lack of efficacy were 1.5% with extended-release acetaminophen and 3.6% and 1.6%, respectively, for low- and high-dose rofecoxib. Dropout due to adverse events occurred in 5.9% of the acetaminophen group, 6.5% with rofecoxib 12.5 mg, and 7.0% with 25 mg. Headache was reported by 6.6% of patients on extended-release acetaminophen, compared with 0.7% on the low dose and 5.4% on the high dose of rofecoxib, Dr. Schnitzer noted. Two patients had an acute MI during the 4-week study, both in the rofecoxib 12.5-mg arm. Investigators deemed the MIs unrelated to the study medication.

The study was sponsored by McNeil Consumer Healthcare.

AMSTERDAM — Extended-release acetaminophen is a possible alternative to cyclooxygenase-2 inhibitors for pain associated with knee osteoarthritis, Dr. Thomas J. Schnitzer reported at the annual European Congress of Rheumatology.

Current osteoarthritis (OA) guidelines recommend the original shorter-acting formulation of acetaminophen at 4 g/day as a first-line treatment for pain associated with the disease. The extended-release formulation, which is commercially available, offers the advantage of less frequent dosing, explained Dr. Schnitzer, professor of medicine at Northwestern University, Chicago.

He reported on 403 adults with knee OA who participated in a 4-week, 23-center, double-blind U.S. clinical trial. Participants were randomized to extended-release acetaminophen at the recommended adult dosage of 1,300 mg t.i.d., rofecoxib at 12.5 mg/day, or rofecoxib at 25 mg/day.

The mean 143.5-mm drop on the 0- to 500-mm visual analog scale in the acetaminophen group was not significantly different from the results with rofecoxib at 12.5 mg/day, but it was inferior to the 175.9-mm drop with high-dose rofecoxib.

Study withdrawal rates for lack of efficacy were 1.5% with extended-release acetaminophen and 3.6% and 1.6%, respectively, for low- and high-dose rofecoxib. Dropout due to adverse events occurred in 5.9% of the acetaminophen group, 6.5% with rofecoxib 12.5 mg, and 7.0% with 25 mg. Headache was reported by 6.6% of patients on extended-release acetaminophen, compared with 0.7% on the low dose and 5.4% on the high dose of rofecoxib, Dr. Schnitzer noted. Two patients had an acute MI during the 4-week study, both in the rofecoxib 12.5-mg arm. Investigators deemed the MIs unrelated to the study medication.

The study was sponsored by McNeil Consumer Healthcare.

GLASGOW, SCOTLAND — Sulfasalazine should be added to the list of drugs that can interfere with assays of urinary catecholamines and their metabolites, Dr. Clive Kelly reported at the annual meeting of the British Society for Rheumatology.

Several medications—including tricyclic antidepressants, antipsychotics, and levodopa—can cause false-positive results when assays for normetanephrine and metanephrine are undertaken to rule out pheochromocytoma. The effect of sulfasalazine on the results of urinary catecholamine assays has not thus far been reported in the literature or to the manufacturers, according to Dr. Kelly, who heads the department of rheumatology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, England.

In one such case of a false-positive pheochromocytoma result, a 48-year-old man with well-controlled rheumatoid arthritis was admitted with a blood pressure reading of 210/130 mm Hg. He had been taking sulfasalazine for 6 years and was then on 1 g/day. His other medications included Calcichew D3 (calcium carbonate plus vitamin D₃), cimetidine, and thyroxine. Initial investigations found nothing remarkable, Dr. Kelly said, but following a 24-hour urine collection, a high-performance liquid chromatography assay found significantly increased levels of normetanephrine at 60.8 μmol/day (the normal range is less than 3.2 μmol/day).

Three repeated analyses during the subsequent 5 months produced similar results, despite that neither MRI nor metaiodobenzylguanidine scintigraphy showed any evidence of a pheochromocytoma, Dr. Kelly wrote in a poster.

To further examine the influence of sulfasalazine on urine collections for fractionated metanephrines, he and his colleagues then prospectively recruited 10 rheumatoid arthritis patients on sulfasalazine who were not hypertensive and were not taking antihypertensive drugs, and 10 age- and sex-matched controls who also were not hypertensive but were not taking sulfasalazine. Both groups provided 24-hour urine collections, which were then analyzed using standard techniques.

The mean level of normetanephrine in the sulfasalazine group was 17.3 μmol/day, compared with 2.4 μmol/day in the control group. The pheochromocytoma false-positive rate was 80% in the sulfasalazine group and 20% in the control group, Dr. Kelly reported. Normetanephrine elevations were not dose dependent.

“We suspect that a metabolite of sulfasalazine forms a peak on the chromatogram close to the position of normetanephrine and is therefore easily misidentified,” he wrote. An alternative explanation is that sulfasalazine may increase endogenous loads of catecholamines or their metabolites.

GLASGOW, SCOTLAND — Sulfasalazine should be added to the list of drugs that can interfere with assays of urinary catecholamines and their metabolites, Dr. Clive Kelly reported at the annual meeting of the British Society for Rheumatology.

Several medications—including tricyclic antidepressants, antipsychotics, and levodopa—can cause false-positive results when assays for normetanephrine and metanephrine are undertaken to rule out pheochromocytoma. The effect of sulfasalazine on the results of urinary catecholamine assays has not thus far been reported in the literature or to the manufacturers, according to Dr. Kelly, who heads the department of rheumatology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, England.

In one such case of a false-positive pheochromocytoma result, a 48-year-old man with well-controlled rheumatoid arthritis was admitted with a blood pressure reading of 210/130 mm Hg. He had been taking sulfasalazine for 6 years and was then on 1 g/day. His other medications included Calcichew D3 (calcium carbonate plus vitamin D₃), cimetidine, and thyroxine. Initial investigations found nothing remarkable, Dr. Kelly said, but following a 24-hour urine collection, a high-performance liquid chromatography assay found significantly increased levels of normetanephrine at 60.8 μmol/day (the normal range is less than 3.2 μmol/day).

Three repeated analyses during the subsequent 5 months produced similar results, despite that neither MRI nor metaiodobenzylguanidine scintigraphy showed any evidence of a pheochromocytoma, Dr. Kelly wrote in a poster.

To further examine the influence of sulfasalazine on urine collections for fractionated metanephrines, he and his colleagues then prospectively recruited 10 rheumatoid arthritis patients on sulfasalazine who were not hypertensive and were not taking antihypertensive drugs, and 10 age- and sex-matched controls who also were not hypertensive but were not taking sulfasalazine. Both groups provided 24-hour urine collections, which were then analyzed using standard techniques.

The mean level of normetanephrine in the sulfasalazine group was 17.3 μmol/day, compared with 2.4 μmol/day in the control group. The pheochromocytoma false-positive rate was 80% in the sulfasalazine group and 20% in the control group, Dr. Kelly reported. Normetanephrine elevations were not dose dependent.

“We suspect that a metabolite of sulfasalazine forms a peak on the chromatogram close to the position of normetanephrine and is therefore easily misidentified,” he wrote. An alternative explanation is that sulfasalazine may increase endogenous loads of catecholamines or their metabolites.

GLASGOW, SCOTLAND — Sulfasalazine should be added to the list of drugs that can interfere with assays of urinary catecholamines and their metabolites, Dr. Clive Kelly reported at the annual meeting of the British Society for Rheumatology.

Several medications—including tricyclic antidepressants, antipsychotics, and levodopa—can cause false-positive results when assays for normetanephrine and metanephrine are undertaken to rule out pheochromocytoma. The effect of sulfasalazine on the results of urinary catecholamine assays has not thus far been reported in the literature or to the manufacturers, according to Dr. Kelly, who heads the department of rheumatology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, England.

In one such case of a false-positive pheochromocytoma result, a 48-year-old man with well-controlled rheumatoid arthritis was admitted with a blood pressure reading of 210/130 mm Hg. He had been taking sulfasalazine for 6 years and was then on 1 g/day. His other medications included Calcichew D3 (calcium carbonate plus vitamin D₃), cimetidine, and thyroxine. Initial investigations found nothing remarkable, Dr. Kelly said, but following a 24-hour urine collection, a high-performance liquid chromatography assay found significantly increased levels of normetanephrine at 60.8 μmol/day (the normal range is less than 3.2 μmol/day).

Three repeated analyses during the subsequent 5 months produced similar results, despite that neither MRI nor metaiodobenzylguanidine scintigraphy showed any evidence of a pheochromocytoma, Dr. Kelly wrote in a poster.

To further examine the influence of sulfasalazine on urine collections for fractionated metanephrines, he and his colleagues then prospectively recruited 10 rheumatoid arthritis patients on sulfasalazine who were not hypertensive and were not taking antihypertensive drugs, and 10 age- and sex-matched controls who also were not hypertensive but were not taking sulfasalazine. Both groups provided 24-hour urine collections, which were then analyzed using standard techniques.

The mean level of normetanephrine in the sulfasalazine group was 17.3 μmol/day, compared with 2.4 μmol/day in the control group. The pheochromocytoma false-positive rate was 80% in the sulfasalazine group and 20% in the control group, Dr. Kelly reported. Normetanephrine elevations were not dose dependent.

“We suspect that a metabolite of sulfasalazine forms a peak on the chromatogram close to the position of normetanephrine and is therefore easily misidentified,” he wrote. An alternative explanation is that sulfasalazine may increase endogenous loads of catecholamines or their metabolites.

CHICAGO — The once-dismissed unicompartmental knee arthroplasty is regaining popularity due to its specific advantages in certain patients, compared with total knee arthroplasty, according to Dr. Bryan J. Nestor of the Hospital for Special Surgery in New York.

“It's an operation that's seen renewed interest over the last 10 years and I think for some good reasons,” Dr. Nestor said at a symposium sponsored by the American College of Rheumatology.

Indications for unicompartmental knee replacement (UKR), also called minimally invasive partial knee surgery, include:

▸ Isolated medial or lateral joint disease.

▸ Minimal and correctable deformity.

▸ Flexion contracture less than 5 degrees.

▸ Flexion greater than 115 degrees.

▸ Patient weight under 200 pounds.

“That leaves about 10% of the patients I see who have severe arthritis of the knee and are candidates for unicompartmental knee replacement,” said Dr. Nestor. He described the procedure as less invasive than total knee arthroplasty (TKA).

“If you're only bending to 110 degrees preoperatively, you're not going to gain that motion postoperatively and are better served with a TKA. However, if you're bending 130–135 degrees, which we sometimes see with isolated unicompartmental arthritis, doing a total knee [arthroplasty] may cause the patient to lose motion and I have to counsel him accordingly, as the average motion after total knee replacement is only about 115 degrees. With a unicompartmental knee I can feel pretty comfortable that I will preserve that 130-degree arc of motion,” he said.

In Dr. Nestor's experience, about half of UKR patients leave the hospital within 2–3 days, and many of these are bending beyond 90 degrees and can do outpatient rehabilitation. Further, many feel better by the 6th week, “whereas with total knee replacement we don't usually see that much self-reported improvement until 3 months,” he said. “More importantly, patients will tell you that the knee feels like a normal knee.”

“This technique is associated with a failure rate of 10%–15% at 10 years, compared with 2% or less for TKA. The unicompartmental procedure can now be revised. Today, a revision of a failed unicompartmental knee replacement approaches the results of a total knee arthroplasty, so we're not burning a bridge and that's why I think the renewed interest in UKR for selected patients is justified.”

CHICAGO — The once-dismissed unicompartmental knee arthroplasty is regaining popularity due to its specific advantages in certain patients, compared with total knee arthroplasty, according to Dr. Bryan J. Nestor of the Hospital for Special Surgery in New York.

“It's an operation that's seen renewed interest over the last 10 years and I think for some good reasons,” Dr. Nestor said at a symposium sponsored by the American College of Rheumatology.

Indications for unicompartmental knee replacement (UKR), also called minimally invasive partial knee surgery, include:

▸ Isolated medial or lateral joint disease.

▸ Minimal and correctable deformity.

▸ Flexion contracture less than 5 degrees.

▸ Flexion greater than 115 degrees.

▸ Patient weight under 200 pounds.

“That leaves about 10% of the patients I see who have severe arthritis of the knee and are candidates for unicompartmental knee replacement,” said Dr. Nestor. He described the procedure as less invasive than total knee arthroplasty (TKA).

“If you're only bending to 110 degrees preoperatively, you're not going to gain that motion postoperatively and are better served with a TKA. However, if you're bending 130–135 degrees, which we sometimes see with isolated unicompartmental arthritis, doing a total knee [arthroplasty] may cause the patient to lose motion and I have to counsel him accordingly, as the average motion after total knee replacement is only about 115 degrees. With a unicompartmental knee I can feel pretty comfortable that I will preserve that 130-degree arc of motion,” he said.

In Dr. Nestor's experience, about half of UKR patients leave the hospital within 2–3 days, and many of these are bending beyond 90 degrees and can do outpatient rehabilitation. Further, many feel better by the 6th week, “whereas with total knee replacement we don't usually see that much self-reported improvement until 3 months,” he said. “More importantly, patients will tell you that the knee feels like a normal knee.”

“This technique is associated with a failure rate of 10%–15% at 10 years, compared with 2% or less for TKA. The unicompartmental procedure can now be revised. Today, a revision of a failed unicompartmental knee replacement approaches the results of a total knee arthroplasty, so we're not burning a bridge and that's why I think the renewed interest in UKR for selected patients is justified.”

CHICAGO — The once-dismissed unicompartmental knee arthroplasty is regaining popularity due to its specific advantages in certain patients, compared with total knee arthroplasty, according to Dr. Bryan J. Nestor of the Hospital for Special Surgery in New York.

“It's an operation that's seen renewed interest over the last 10 years and I think for some good reasons,” Dr. Nestor said at a symposium sponsored by the American College of Rheumatology.

Indications for unicompartmental knee replacement (UKR), also called minimally invasive partial knee surgery, include:

▸ Isolated medial or lateral joint disease.

▸ Minimal and correctable deformity.

▸ Flexion contracture less than 5 degrees.

▸ Flexion greater than 115 degrees.

▸ Patient weight under 200 pounds.

“That leaves about 10% of the patients I see who have severe arthritis of the knee and are candidates for unicompartmental knee replacement,” said Dr. Nestor. He described the procedure as less invasive than total knee arthroplasty (TKA).

“If you're only bending to 110 degrees preoperatively, you're not going to gain that motion postoperatively and are better served with a TKA. However, if you're bending 130–135 degrees, which we sometimes see with isolated unicompartmental arthritis, doing a total knee [arthroplasty] may cause the patient to lose motion and I have to counsel him accordingly, as the average motion after total knee replacement is only about 115 degrees. With a unicompartmental knee I can feel pretty comfortable that I will preserve that 130-degree arc of motion,” he said.

In Dr. Nestor's experience, about half of UKR patients leave the hospital within 2–3 days, and many of these are bending beyond 90 degrees and can do outpatient rehabilitation. Further, many feel better by the 6th week, “whereas with total knee replacement we don't usually see that much self-reported improvement until 3 months,” he said. “More importantly, patients will tell you that the knee feels like a normal knee.”

“This technique is associated with a failure rate of 10%–15% at 10 years, compared with 2% or less for TKA. The unicompartmental procedure can now be revised. Today, a revision of a failed unicompartmental knee replacement approaches the results of a total knee arthroplasty, so we're not burning a bridge and that's why I think the renewed interest in UKR for selected patients is justified.”

SAN DIEGO — Participation in a program that incorporated mindfulness meditation and yoga resulted in a statistically significant reduction in psychological distress in a pilot study of patients with rheumatoid arthritis, Elizabeth Kimbrough Pradhan, Ph.D., reported at the annual meeting of the American College of Rheumatology.

A group of 63 adults with rheumatoid arthritis (RA) was randomized to either a 2.5-hour mindfulness-based stress reduction class once a week for 8 weeks or to a wait-list control group.

Mindfulness meditation involves the cultivation of moment-to-moment awareness and attention, against a backdrop of compassion for oneself and others, said Dr. Pradhan of the Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore. Participants learned meditation techniques and hatha yoga postures, and were asked to practice at home for 45 minutes to an hour 6 days each week.

RA disease status was evaluated by Disease Activity Score (DAS) 28, while psychological distress was measured by the Symptom Checklist-90-Revised. Patients were predominantly female, educated, and of mid to high socioeconomic status. All were under the regular care of a rheumatologist, with 74% taking disease modifying antirheumatic drugs, 15.9% being prescribed biologic agents, 50.8% taking nonsteroidal anti-inflammatory drugs, and 31.8% using corticosteroids.

In the meditation group, there was a 30% reduction in psychological distress at 2 months, which was a statistically significant change, Dr. Pradhan said. The 10% decrease seen in the control group was not significant.

At 6 months, a statistically significant 33% reduction in psychological distress was seen in the meditation group, compared with a nonsignificant 2% decrease in the control group.

The mean DAS28 at baseline was 3.1 in the treatment group and 3.3 in the control group, indicating moderate disease activity. Mean erythrocyte sedimentation rate (ESR) was 22.1 in both groups.

There was no change in disease activity in either group by 2 months, but by 6 months there was an 11% decrease in the meditation group. This was statistically significant but would not be considered clinically significant by experts, Dr. Pradhan said. “Nonetheless, what was interesting was that of the four components in the DAS28, the one driving the change was ESR,” she said during a press briefing. There was a statistically significant 23% reduction in ESR from baseline to 2 months in the meditation group, and a statistically significant 33% decrease from baseline to 6 months. At both of these time points, there were slight increases in ESR in the control group. As to why the ESR would have decreased in response to meditation, Dr. Pradhan offered several possible explanations. One was that the meditation group may have modified lifestyle factors.

“If participants in the meditation group were feeling better as a result of being in the mindfulness-based stress reduction course, it is possible that they could have changed their diets to include more fruits and vegetables, reduced fried and sugary foods and so forth, which may have contributed to a decrease in general inflammation,” she explained.

Another possible explanation could be a proinflammatory response to stress, involving activation of the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system, she offered. Emotional responses to stress register in the hippocampus, causing the release of corticotropin-releasing hormone (CRH), which stimulates the HPA axis, ultimately resulting in the release of epinephrine and other hormones. CRH and norepinephrine are released peripherally through the response of the autonomic nervous system.

“A CRH receptor-dependent inflammatory response in RA synovial tissue has been observed, and CRH has been seen to up-regulate prostaglandin production in RA synovial tissue in a dose-response manner,” she said.

CRH, norepinephrine, and epinephrine may also potentiate inflammation in RA by activating macrophages that release interleukin (IL)-1, IL-6, and tumor necrosis factor-α and through up-regulation of β-adrenoceptors for norepinephrine that results in increased IL-6 secretion, Dr. Pradhan added.

SAN DIEGO — Participation in a program that incorporated mindfulness meditation and yoga resulted in a statistically significant reduction in psychological distress in a pilot study of patients with rheumatoid arthritis, Elizabeth Kimbrough Pradhan, Ph.D., reported at the annual meeting of the American College of Rheumatology.

A group of 63 adults with rheumatoid arthritis (RA) was randomized to either a 2.5-hour mindfulness-based stress reduction class once a week for 8 weeks or to a wait-list control group.

Mindfulness meditation involves the cultivation of moment-to-moment awareness and attention, against a backdrop of compassion for oneself and others, said Dr. Pradhan of the Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore. Participants learned meditation techniques and hatha yoga postures, and were asked to practice at home for 45 minutes to an hour 6 days each week.

RA disease status was evaluated by Disease Activity Score (DAS) 28, while psychological distress was measured by the Symptom Checklist-90-Revised. Patients were predominantly female, educated, and of mid to high socioeconomic status. All were under the regular care of a rheumatologist, with 74% taking disease modifying antirheumatic drugs, 15.9% being prescribed biologic agents, 50.8% taking nonsteroidal anti-inflammatory drugs, and 31.8% using corticosteroids.

In the meditation group, there was a 30% reduction in psychological distress at 2 months, which was a statistically significant change, Dr. Pradhan said. The 10% decrease seen in the control group was not significant.

At 6 months, a statistically significant 33% reduction in psychological distress was seen in the meditation group, compared with a nonsignificant 2% decrease in the control group.

The mean DAS28 at baseline was 3.1 in the treatment group and 3.3 in the control group, indicating moderate disease activity. Mean erythrocyte sedimentation rate (ESR) was 22.1 in both groups.

There was no change in disease activity in either group by 2 months, but by 6 months there was an 11% decrease in the meditation group. This was statistically significant but would not be considered clinically significant by experts, Dr. Pradhan said. “Nonetheless, what was interesting was that of the four components in the DAS28, the one driving the change was ESR,” she said during a press briefing. There was a statistically significant 23% reduction in ESR from baseline to 2 months in the meditation group, and a statistically significant 33% decrease from baseline to 6 months. At both of these time points, there were slight increases in ESR in the control group. As to why the ESR would have decreased in response to meditation, Dr. Pradhan offered several possible explanations. One was that the meditation group may have modified lifestyle factors.

“If participants in the meditation group were feeling better as a result of being in the mindfulness-based stress reduction course, it is possible that they could have changed their diets to include more fruits and vegetables, reduced fried and sugary foods and so forth, which may have contributed to a decrease in general inflammation,” she explained.

Another possible explanation could be a proinflammatory response to stress, involving activation of the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system, she offered. Emotional responses to stress register in the hippocampus, causing the release of corticotropin-releasing hormone (CRH), which stimulates the HPA axis, ultimately resulting in the release of epinephrine and other hormones. CRH and norepinephrine are released peripherally through the response of the autonomic nervous system.

“A CRH receptor-dependent inflammatory response in RA synovial tissue has been observed, and CRH has been seen to up-regulate prostaglandin production in RA synovial tissue in a dose-response manner,” she said.

CRH, norepinephrine, and epinephrine may also potentiate inflammation in RA by activating macrophages that release interleukin (IL)-1, IL-6, and tumor necrosis factor-α and through up-regulation of β-adrenoceptors for norepinephrine that results in increased IL-6 secretion, Dr. Pradhan added.

SAN DIEGO — Participation in a program that incorporated mindfulness meditation and yoga resulted in a statistically significant reduction in psychological distress in a pilot study of patients with rheumatoid arthritis, Elizabeth Kimbrough Pradhan, Ph.D., reported at the annual meeting of the American College of Rheumatology.

A group of 63 adults with rheumatoid arthritis (RA) was randomized to either a 2.5-hour mindfulness-based stress reduction class once a week for 8 weeks or to a wait-list control group.

Mindfulness meditation involves the cultivation of moment-to-moment awareness and attention, against a backdrop of compassion for oneself and others, said Dr. Pradhan of the Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore. Participants learned meditation techniques and hatha yoga postures, and were asked to practice at home for 45 minutes to an hour 6 days each week.

RA disease status was evaluated by Disease Activity Score (DAS) 28, while psychological distress was measured by the Symptom Checklist-90-Revised. Patients were predominantly female, educated, and of mid to high socioeconomic status. All were under the regular care of a rheumatologist, with 74% taking disease modifying antirheumatic drugs, 15.9% being prescribed biologic agents, 50.8% taking nonsteroidal anti-inflammatory drugs, and 31.8% using corticosteroids.

In the meditation group, there was a 30% reduction in psychological distress at 2 months, which was a statistically significant change, Dr. Pradhan said. The 10% decrease seen in the control group was not significant.

At 6 months, a statistically significant 33% reduction in psychological distress was seen in the meditation group, compared with a nonsignificant 2% decrease in the control group.

The mean DAS28 at baseline was 3.1 in the treatment group and 3.3 in the control group, indicating moderate disease activity. Mean erythrocyte sedimentation rate (ESR) was 22.1 in both groups.

There was no change in disease activity in either group by 2 months, but by 6 months there was an 11% decrease in the meditation group. This was statistically significant but would not be considered clinically significant by experts, Dr. Pradhan said. “Nonetheless, what was interesting was that of the four components in the DAS28, the one driving the change was ESR,” she said during a press briefing. There was a statistically significant 23% reduction in ESR from baseline to 2 months in the meditation group, and a statistically significant 33% decrease from baseline to 6 months. At both of these time points, there were slight increases in ESR in the control group. As to why the ESR would have decreased in response to meditation, Dr. Pradhan offered several possible explanations. One was that the meditation group may have modified lifestyle factors.

“If participants in the meditation group were feeling better as a result of being in the mindfulness-based stress reduction course, it is possible that they could have changed their diets to include more fruits and vegetables, reduced fried and sugary foods and so forth, which may have contributed to a decrease in general inflammation,” she explained.

Another possible explanation could be a proinflammatory response to stress, involving activation of the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system, she offered. Emotional responses to stress register in the hippocampus, causing the release of corticotropin-releasing hormone (CRH), which stimulates the HPA axis, ultimately resulting in the release of epinephrine and other hormones. CRH and norepinephrine are released peripherally through the response of the autonomic nervous system.

“A CRH receptor-dependent inflammatory response in RA synovial tissue has been observed, and CRH has been seen to up-regulate prostaglandin production in RA synovial tissue in a dose-response manner,” she said.

CRH, norepinephrine, and epinephrine may also potentiate inflammation in RA by activating macrophages that release interleukin (IL)-1, IL-6, and tumor necrosis factor-α and through up-regulation of β-adrenoceptors for norepinephrine that results in increased IL-6 secretion, Dr. Pradhan added.

Both diagnostic and therapeutic injections for shoulder pain are often placed inaccurately, even when clinicians are convinced they've injected the subacromial bursa rather than other structures, reported Dr. Hans-Erik Henkus of Medisch Centrum Haaglanden, the Hague, and his associates.

They found that only 66% of subacromial injections were accurate in a series of 33 patients, suggesting that the technique is “a poor tool” for diagnosing the source of shoulder pain and “worrisome” as a therapeutic strategy, the researchers said.

Rather than easing pain and restoring function, inaccurate injections worsen both.

Injecting a local anesthetic around the shoulder area is a widely used method for determining the source of the pain and for predicting the success of subacromial decompression surgery. Injecting corticosteroids is done to reduce inflammation and pain. Both strategies are “based on the assumption that these injections can be given with great accuracy,” Dr. Henkus and his associates wrote (Arthroscopy 2006;22:277–82).

But few studies have examined the accuracy of shoulder injections.

The investigators assessed the technique in 33 patients with nontraumatic shoulder pain localized to the deltoid region. The 11 men and 22 women, with an average age of 46 years, were unable to lie on the affected side. Abduction, retroversion, or internal rotation of the glenohumeral joint against resistance provoked further pain.

With the subjects in an upright seated position, an experienced orthopedic surgeon injected all the shoulders with a mixture of bupivacaine, methylprednisolone, and a contrast agent. The surgeon was randomly assigned to approach either anteromedially (16 cases) or posteriorly (17 cases). An MRI was performed immediately to determine the location of the infiltration.

The subacromial bursa was accurately targeted in only 22 (66%) of cases, even though the surgeon was confident that the injections had been accurate in 30 cases (91%) and “doubtful” in only 3.

Three injections infiltrated only the deltoid muscle and subcutaneous tissue, two the glenohumeral joint only, two the acromioclavicular joint only, and three the rotator cuff only.

Even when the subacromial bursa was correctly targeted, many surrounding tissues were infiltrated as well. The rotator cuff was infiltrated 13 times, the deltoid muscle 3 times, and the coracoacromial ligament 2 times.

Pain was reduced and function improved in the cases in which the subacromial bursa alone was injected. However, pain increased and function declined or showed no change when other structures, particularly the rotator cuff, were infiltrated.

“The rotator cuff muscle or tendon was hit in 17 patients,” a “worrisome” incidence that could well have caused rotator cuff rupture, particularly if corticosteroids had been injected, the investigators noted.

Neither the type of approach (anterior or posterior) nor the patient's body mass index had any influence on the accuracy of injection placement.

Given that a single faulty injection to any of a variety of structures could produce either a false-positive or a false-negative result, these findings indicate that “the diagnostic use of local injections in the subacromial bursa [is] a poor tool,” they said.

Both diagnostic and therapeutic injections for shoulder pain are often placed inaccurately, even when clinicians are convinced they've injected the subacromial bursa rather than other structures, reported Dr. Hans-Erik Henkus of Medisch Centrum Haaglanden, the Hague, and his associates.

They found that only 66% of subacromial injections were accurate in a series of 33 patients, suggesting that the technique is “a poor tool” for diagnosing the source of shoulder pain and “worrisome” as a therapeutic strategy, the researchers said.

Rather than easing pain and restoring function, inaccurate injections worsen both.

Injecting a local anesthetic around the shoulder area is a widely used method for determining the source of the pain and for predicting the success of subacromial decompression surgery. Injecting corticosteroids is done to reduce inflammation and pain. Both strategies are “based on the assumption that these injections can be given with great accuracy,” Dr. Henkus and his associates wrote (Arthroscopy 2006;22:277–82).

But few studies have examined the accuracy of shoulder injections.

The investigators assessed the technique in 33 patients with nontraumatic shoulder pain localized to the deltoid region. The 11 men and 22 women, with an average age of 46 years, were unable to lie on the affected side. Abduction, retroversion, or internal rotation of the glenohumeral joint against resistance provoked further pain.

With the subjects in an upright seated position, an experienced orthopedic surgeon injected all the shoulders with a mixture of bupivacaine, methylprednisolone, and a contrast agent. The surgeon was randomly assigned to approach either anteromedially (16 cases) or posteriorly (17 cases). An MRI was performed immediately to determine the location of the infiltration.

The subacromial bursa was accurately targeted in only 22 (66%) of cases, even though the surgeon was confident that the injections had been accurate in 30 cases (91%) and “doubtful” in only 3.

Three injections infiltrated only the deltoid muscle and subcutaneous tissue, two the glenohumeral joint only, two the acromioclavicular joint only, and three the rotator cuff only.

Even when the subacromial bursa was correctly targeted, many surrounding tissues were infiltrated as well. The rotator cuff was infiltrated 13 times, the deltoid muscle 3 times, and the coracoacromial ligament 2 times.

Pain was reduced and function improved in the cases in which the subacromial bursa alone was injected. However, pain increased and function declined or showed no change when other structures, particularly the rotator cuff, were infiltrated.

“The rotator cuff muscle or tendon was hit in 17 patients,” a “worrisome” incidence that could well have caused rotator cuff rupture, particularly if corticosteroids had been injected, the investigators noted.

Neither the type of approach (anterior or posterior) nor the patient's body mass index had any influence on the accuracy of injection placement.

Given that a single faulty injection to any of a variety of structures could produce either a false-positive or a false-negative result, these findings indicate that “the diagnostic use of local injections in the subacromial bursa [is] a poor tool,” they said.

Both diagnostic and therapeutic injections for shoulder pain are often placed inaccurately, even when clinicians are convinced they've injected the subacromial bursa rather than other structures, reported Dr. Hans-Erik Henkus of Medisch Centrum Haaglanden, the Hague, and his associates.

They found that only 66% of subacromial injections were accurate in a series of 33 patients, suggesting that the technique is “a poor tool” for diagnosing the source of shoulder pain and “worrisome” as a therapeutic strategy, the researchers said.

Rather than easing pain and restoring function, inaccurate injections worsen both.

Injecting a local anesthetic around the shoulder area is a widely used method for determining the source of the pain and for predicting the success of subacromial decompression surgery. Injecting corticosteroids is done to reduce inflammation and pain. Both strategies are “based on the assumption that these injections can be given with great accuracy,” Dr. Henkus and his associates wrote (Arthroscopy 2006;22:277–82).

But few studies have examined the accuracy of shoulder injections.

The investigators assessed the technique in 33 patients with nontraumatic shoulder pain localized to the deltoid region. The 11 men and 22 women, with an average age of 46 years, were unable to lie on the affected side. Abduction, retroversion, or internal rotation of the glenohumeral joint against resistance provoked further pain.

With the subjects in an upright seated position, an experienced orthopedic surgeon injected all the shoulders with a mixture of bupivacaine, methylprednisolone, and a contrast agent. The surgeon was randomly assigned to approach either anteromedially (16 cases) or posteriorly (17 cases). An MRI was performed immediately to determine the location of the infiltration.

The subacromial bursa was accurately targeted in only 22 (66%) of cases, even though the surgeon was confident that the injections had been accurate in 30 cases (91%) and “doubtful” in only 3.

Three injections infiltrated only the deltoid muscle and subcutaneous tissue, two the glenohumeral joint only, two the acromioclavicular joint only, and three the rotator cuff only.

Even when the subacromial bursa was correctly targeted, many surrounding tissues were infiltrated as well. The rotator cuff was infiltrated 13 times, the deltoid muscle 3 times, and the coracoacromial ligament 2 times.

Pain was reduced and function improved in the cases in which the subacromial bursa alone was injected. However, pain increased and function declined or showed no change when other structures, particularly the rotator cuff, were infiltrated.

“The rotator cuff muscle or tendon was hit in 17 patients,” a “worrisome” incidence that could well have caused rotator cuff rupture, particularly if corticosteroids had been injected, the investigators noted.

Neither the type of approach (anterior or posterior) nor the patient's body mass index had any influence on the accuracy of injection placement.

Given that a single faulty injection to any of a variety of structures could produce either a false-positive or a false-negative result, these findings indicate that “the diagnostic use of local injections in the subacromial bursa [is] a poor tool,” they said.