Rheumatoid Arthritis

KEVIN FOLEY, RESEARCH/ELSEVIER GLOBAL MEDICAL NEWS

KEVIN FOLEY, RESEARCH/ELSEVIER GLOBAL MEDICAL NEWS

KEVIN FOLEY, RESEARCH/ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” said Dr. Reginato.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5 kg metal disk onto a table.

During the tasks, ankle, knee, hip, and back MEE and MEC were calculated. Maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task were also assessed.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, Dr. Reginato said.

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” said Dr. Reginato.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5 kg metal disk onto a table.

During the tasks, ankle, knee, hip, and back MEE and MEC were calculated. Maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task were also assessed.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, Dr. Reginato said.

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” said Dr. Reginato.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5 kg metal disk onto a table.

During the tasks, ankle, knee, hip, and back MEE and MEC were calculated. Maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task were also assessed.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, Dr. Reginato said.

HONOLULU — Even over-the-counter doses of nonselective NSAIDs significantly increase the risk of serious GI complications, Joseph Biskupiak, Ph.D., said at the annual meeting of the American College of Gastroenterology.

Moreover, his study of a large, national outpatient primary care database of electronic medical records showed that this risk is further intensified by concomitant use of low-dose aspirin, added Dr. Biskupiak of the University of Utah College of Pharmacy, Salt Lake City.

“I think there are a couple of take-home messages here for the patient and physician populations. It's that [over-the-counter] NSAIDs are not benign. As physicians, you need to assess patient usage of these medications and inform them of the associated risks. And patients taking these medications need to discuss their use with their physician,” he said.

Dr. Biskupiak reviewed the 3.2-million-patient GE Medical Systems Centricity database and identified 11,957 individuals taking OTC naproxen at 220 mg/day and 38,507 taking OTC ibuprofen at 200 mg/day who were free of medical conditions or therapies that would predispose to GI bleeding. He compared the incidence of GI perforations, ulcers, or bleeding (PUB) during the first 3 months after taking the NSAID—even a single dose—with the rates during the 6- and 12-month periods prior to taking either NSAID.

In the 6 months prior to taking ibuprofen, 55 patients experienced a PUB, as did 100 in the year prior to taking the drug. During the 3 months after starting on ibuprofen, patients were 2.5 times more likely to experience a PUB than in the previous 6 months, and 38% more likely to experience a PUB than in the year prior to taking the NSAID.

Similarly, patients who took naproxen were 2.74 times more likely to develop PUBs than in the 6 months before taking the drug, and 54% more likely than in the year beforehand, he continued.

Concurrent low-dose aspirin was used by 2,328 patients who took naproxen; their risk of developing a PUB was twice that of patients on naproxen alone. The 4,843 patients on low-dose aspirin and ibuprofen were 3.36 times more likely to develop a PUB within 3 months of starting the NSAID than patients taking ibuprofen alone.

Session cochair Dr. David Y. Graham questioned the clinical relevance of Dr. Biskupiak's findings.

“The actual PUB complication rates with [over-the-counter] NSAIDs were maybe 1 in 200 patients per year. In the control group, it would be a little less than that. That's an extraordinarily low number. The question is, is it clinically important?” asked Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

Dr. Biskupiak's answer was emphatically yes. “Considering that we're talking about an estimated 60 million Americans using OTC pain medications daily—many of whom are unaware that NSAIDs can cause major GI problems—even though 1 in 200 is a very small number, it turns out to be a significant total number of people,” noted Dr. Biskupiak. “And remember: More than 100,000 hospitalizations annually … are attributed to GI complications of NSAID usage.”

His study was funded by Pfizer Inc.

NSAIDs are not benign. Patients taking them need to be informed of the associated risks. DR. BISKUPIAK

HONOLULU — Even over-the-counter doses of nonselective NSAIDs significantly increase the risk of serious GI complications, Joseph Biskupiak, Ph.D., said at the annual meeting of the American College of Gastroenterology.

Moreover, his study of a large, national outpatient primary care database of electronic medical records showed that this risk is further intensified by concomitant use of low-dose aspirin, added Dr. Biskupiak of the University of Utah College of Pharmacy, Salt Lake City.

“I think there are a couple of take-home messages here for the patient and physician populations. It's that [over-the-counter] NSAIDs are not benign. As physicians, you need to assess patient usage of these medications and inform them of the associated risks. And patients taking these medications need to discuss their use with their physician,” he said.

Dr. Biskupiak reviewed the 3.2-million-patient GE Medical Systems Centricity database and identified 11,957 individuals taking OTC naproxen at 220 mg/day and 38,507 taking OTC ibuprofen at 200 mg/day who were free of medical conditions or therapies that would predispose to GI bleeding. He compared the incidence of GI perforations, ulcers, or bleeding (PUB) during the first 3 months after taking the NSAID—even a single dose—with the rates during the 6- and 12-month periods prior to taking either NSAID.

In the 6 months prior to taking ibuprofen, 55 patients experienced a PUB, as did 100 in the year prior to taking the drug. During the 3 months after starting on ibuprofen, patients were 2.5 times more likely to experience a PUB than in the previous 6 months, and 38% more likely to experience a PUB than in the year prior to taking the NSAID.

Similarly, patients who took naproxen were 2.74 times more likely to develop PUBs than in the 6 months before taking the drug, and 54% more likely than in the year beforehand, he continued.

Concurrent low-dose aspirin was used by 2,328 patients who took naproxen; their risk of developing a PUB was twice that of patients on naproxen alone. The 4,843 patients on low-dose aspirin and ibuprofen were 3.36 times more likely to develop a PUB within 3 months of starting the NSAID than patients taking ibuprofen alone.

Session cochair Dr. David Y. Graham questioned the clinical relevance of Dr. Biskupiak's findings.

“The actual PUB complication rates with [over-the-counter] NSAIDs were maybe 1 in 200 patients per year. In the control group, it would be a little less than that. That's an extraordinarily low number. The question is, is it clinically important?” asked Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

Dr. Biskupiak's answer was emphatically yes. “Considering that we're talking about an estimated 60 million Americans using OTC pain medications daily—many of whom are unaware that NSAIDs can cause major GI problems—even though 1 in 200 is a very small number, it turns out to be a significant total number of people,” noted Dr. Biskupiak. “And remember: More than 100,000 hospitalizations annually … are attributed to GI complications of NSAID usage.”

His study was funded by Pfizer Inc.

NSAIDs are not benign. Patients taking them need to be informed of the associated risks. DR. BISKUPIAK

HONOLULU — Even over-the-counter doses of nonselective NSAIDs significantly increase the risk of serious GI complications, Joseph Biskupiak, Ph.D., said at the annual meeting of the American College of Gastroenterology.

Moreover, his study of a large, national outpatient primary care database of electronic medical records showed that this risk is further intensified by concomitant use of low-dose aspirin, added Dr. Biskupiak of the University of Utah College of Pharmacy, Salt Lake City.

“I think there are a couple of take-home messages here for the patient and physician populations. It's that [over-the-counter] NSAIDs are not benign. As physicians, you need to assess patient usage of these medications and inform them of the associated risks. And patients taking these medications need to discuss their use with their physician,” he said.

Dr. Biskupiak reviewed the 3.2-million-patient GE Medical Systems Centricity database and identified 11,957 individuals taking OTC naproxen at 220 mg/day and 38,507 taking OTC ibuprofen at 200 mg/day who were free of medical conditions or therapies that would predispose to GI bleeding. He compared the incidence of GI perforations, ulcers, or bleeding (PUB) during the first 3 months after taking the NSAID—even a single dose—with the rates during the 6- and 12-month periods prior to taking either NSAID.

In the 6 months prior to taking ibuprofen, 55 patients experienced a PUB, as did 100 in the year prior to taking the drug. During the 3 months after starting on ibuprofen, patients were 2.5 times more likely to experience a PUB than in the previous 6 months, and 38% more likely to experience a PUB than in the year prior to taking the NSAID.

Similarly, patients who took naproxen were 2.74 times more likely to develop PUBs than in the 6 months before taking the drug, and 54% more likely than in the year beforehand, he continued.

Concurrent low-dose aspirin was used by 2,328 patients who took naproxen; their risk of developing a PUB was twice that of patients on naproxen alone. The 4,843 patients on low-dose aspirin and ibuprofen were 3.36 times more likely to develop a PUB within 3 months of starting the NSAID than patients taking ibuprofen alone.

Session cochair Dr. David Y. Graham questioned the clinical relevance of Dr. Biskupiak's findings.

“The actual PUB complication rates with [over-the-counter] NSAIDs were maybe 1 in 200 patients per year. In the control group, it would be a little less than that. That's an extraordinarily low number. The question is, is it clinically important?” asked Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

Dr. Biskupiak's answer was emphatically yes. “Considering that we're talking about an estimated 60 million Americans using OTC pain medications daily—many of whom are unaware that NSAIDs can cause major GI problems—even though 1 in 200 is a very small number, it turns out to be a significant total number of people,” noted Dr. Biskupiak. “And remember: More than 100,000 hospitalizations annually … are attributed to GI complications of NSAID usage.”

His study was funded by Pfizer Inc.

NSAIDs are not benign. Patients taking them need to be informed of the associated risks. DR. BISKUPIAK

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

Limiting Tunnel Widening in ACL Repair

A novel hamstring anterior cruciate ligament reconstruction technique that uses a shorter, more rigidly fixed graft prevents the tunnel widening that can lead to a bungee-cord effect following ACL repair.

Dr. Peter Fauno of Randers (Denmark) Central Hospital and colleagues randomly assigned 100 patients to undergo either the new technique using a transfemoral fixation implant with an interference screw in the tibial tunnel, or extracortical fixation in the femur with a bicortical screw and washer distal to the tibial tunnel. A total of 87 patients were available for assessment at 1-year follow-up.

Patients who underwent the new technique had a lower incidence of tunnel widening, compared with those in the conventional technique group (Arthroscopy 2005;21:1337–41.)

A total of 7 of 41 patients (17%) undergoing transfemoral fixation implantation with an interference screw in the tibial tunnel experienced femoral tunnel widening; 5 patients (12%) in that group experienced tibial tunnel widening.

By comparison, 20 of 46 patients (44%) who received extracortical fixation had femoral tunnel widening; 16 patients (35%) in that group had tibial tunnel widening.

Despite the similarity in clinical outcome at 1 year and assuming tunnel widening has no clinical implications, Dr. Fauno believes the risk of tunnel widening should be kept as low as possible.

Vitamin D Beats Calcium for Bones

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Vitamin D supplements should be recommended “when sun exposure and dietary sources are insufficient,” Dr. Steingrimsdottir and associates said.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxyvitamin D for maintaining calcium homeostasis in a study of 944 healthy white adult residents of Iceland. The 491 women and 453 men were aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, a marker of bone health, even when calcium intake was not sufficient to maintain those PTH levels. In contrast, high calcium intake did not make up for decreased vitamin D.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were found to be dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Our study indicates that as long as vitamin D status is secured by vitamin D, supplements or sufficient sunshine calcium intake levels of more than 800 mg [per day] may be unnecessary,” the investigators noted.

Botox Effective for Tennis Elbow Pain

Botulinum toxin injections may provide short-term pain relief for patients with lateral epicondylitis, Chinese researchers have reported.

A randomized, placebo-controlled trial of botulinum toxin in 60 patients with lateral epicondylitis was conducted at Prince of Wales Hospital in Hong Kong. Dr. Shiu Man Wong and colleagues administered either a single 60-unit injection of botulinum toxin type A or an equivalent volume of normal saline to patients.

Baseline pain scores, using a 100-mm visual analog scale (VAS) of 65.5 mm at baseline, improved to a score of 25.4 mm at 4 weeks in patients receiving botulinum toxin. In controls, the VAS score was 66 mm at baseline and 51 mm at 4 weeks (Ann. Intern. Med. 2005;143:793–7).

Twelve weeks after injection, VAS scores were 23.5 mm for the study group and 43.5 mm for controls.

Mild paresis of the fingers was found at the 4-week check in four patients in the study group, with symptoms persisting in one patient through 12 weeks of follow-up. No patient in the placebo group developed finger paresis. Weak finger extension in the affected limb was noted in 10 patients who received botulinum toxin and in 6 patients in the placebo group.

There was no significant difference in grip strength between the two groups during the study period.

SAN DIEGO — Microfracture as a treatment for full thickness chondral lesions provided functional improvement in a group of professional and recreational athletes at 6-year follow-up, but the level of postoperative sports participation declined with time, Dr. Alberto Gobbi reported at a symposium sponsored by the International Cartilage Repair Society.

The finding suggests that while microfracture can be performed as a simple, minimally invasive method to promote cartilage healing, it “may not be the definitive treatment for the athletes' knee, as further procedures may be indicated in the future,” said Dr. Gobbi, an orthopedic surgeon with the Orthopedic Arthroscopic Surgery International Research Center in Milan. “However, it can relieve symptoms and delay the need for further treatment.”

Dr. Gobbi and his associate Dr. Ramces Francisco followed 53 professional and recreational athletes who underwent microfracture surgery for unilateral knee articular cartilage injury at their center. Mean patient age was 38 years. Of the patients, 33 were male, and 26 were professional athletes. Mean follow-up was 6 years.

Outcomes were assessed using the Lysholm score, Tegner activity level score, the International Knee Documentation Committee (IKDC) scoring system, and a subjective evaluation based on a 100-point scale. Roentgenograms, MRI, or CT scans were done pre- and postoperatively.

Dr. Gobbi reported that the cause of most injuries was related to sports microtrauma (38%) and macrotrauma (21%), although 38% of patients did not report any traumatic etiology and 4% showed patellar malalignment. The most common location of injury was the medial femoral condyle (61%), and the mean defect size among study participants was 4 cm

Between baseline and final follow-up the mean Lysholm scores improved from 57 to 87; the Tegner scores improved from 3 to 5; and the subjective evaluation improved from 40/100 to 70/100. At baseline, only three patients scored an A or B on the IKDC, but by final follow-up, 70% of patients scored an A or B.

Also by final follow-up, activities of daily living improved in 65% of patients while imaging studies revealed increased degenerative changes in 30% of patients.

“When we analyzed the [return to] strenuous sports activities, we found they increased to 80% in the first 2 years but then gradually decreased to 55% at final follow-up,” Dr. Gobbi added. Changing to a low-risk sport, advancing age of the study participants, work and family obligations, and the influence of degenerative joint disease may have contributed to the decline in postsurgical sports activity.

Second-look arthroscopy performed in 10 patients showed that the articular defects were covered with fibrocartilaginous tissue at a level adjacent with normal articular surface and were firm when palpated with a probe. Biopsies from these same 10 patients showed areas of fibromyxoid tissue with differentiation, a transition zone with cartilage tissue, and initial hyaline transformation tissue.

Candidates should be evaluated by age, activity level, type of sport, type of injury, expectations, associated pathologies, likelihood of rehabilitation compliance, and the articular depth of the defect.

SAN DIEGO — Microfracture as a treatment for full thickness chondral lesions provided functional improvement in a group of professional and recreational athletes at 6-year follow-up, but the level of postoperative sports participation declined with time, Dr. Alberto Gobbi reported at a symposium sponsored by the International Cartilage Repair Society.

The finding suggests that while microfracture can be performed as a simple, minimally invasive method to promote cartilage healing, it “may not be the definitive treatment for the athletes' knee, as further procedures may be indicated in the future,” said Dr. Gobbi, an orthopedic surgeon with the Orthopedic Arthroscopic Surgery International Research Center in Milan. “However, it can relieve symptoms and delay the need for further treatment.”

Dr. Gobbi and his associate Dr. Ramces Francisco followed 53 professional and recreational athletes who underwent microfracture surgery for unilateral knee articular cartilage injury at their center. Mean patient age was 38 years. Of the patients, 33 were male, and 26 were professional athletes. Mean follow-up was 6 years.

Outcomes were assessed using the Lysholm score, Tegner activity level score, the International Knee Documentation Committee (IKDC) scoring system, and a subjective evaluation based on a 100-point scale. Roentgenograms, MRI, or CT scans were done pre- and postoperatively.

Dr. Gobbi reported that the cause of most injuries was related to sports microtrauma (38%) and macrotrauma (21%), although 38% of patients did not report any traumatic etiology and 4% showed patellar malalignment. The most common location of injury was the medial femoral condyle (61%), and the mean defect size among study participants was 4 cm

Between baseline and final follow-up the mean Lysholm scores improved from 57 to 87; the Tegner scores improved from 3 to 5; and the subjective evaluation improved from 40/100 to 70/100. At baseline, only three patients scored an A or B on the IKDC, but by final follow-up, 70% of patients scored an A or B.

Also by final follow-up, activities of daily living improved in 65% of patients while imaging studies revealed increased degenerative changes in 30% of patients.

“When we analyzed the [return to] strenuous sports activities, we found they increased to 80% in the first 2 years but then gradually decreased to 55% at final follow-up,” Dr. Gobbi added. Changing to a low-risk sport, advancing age of the study participants, work and family obligations, and the influence of degenerative joint disease may have contributed to the decline in postsurgical sports activity.

Second-look arthroscopy performed in 10 patients showed that the articular defects were covered with fibrocartilaginous tissue at a level adjacent with normal articular surface and were firm when palpated with a probe. Biopsies from these same 10 patients showed areas of fibromyxoid tissue with differentiation, a transition zone with cartilage tissue, and initial hyaline transformation tissue.

Candidates should be evaluated by age, activity level, type of sport, type of injury, expectations, associated pathologies, likelihood of rehabilitation compliance, and the articular depth of the defect.

SAN DIEGO — Microfracture as a treatment for full thickness chondral lesions provided functional improvement in a group of professional and recreational athletes at 6-year follow-up, but the level of postoperative sports participation declined with time, Dr. Alberto Gobbi reported at a symposium sponsored by the International Cartilage Repair Society.

The finding suggests that while microfracture can be performed as a simple, minimally invasive method to promote cartilage healing, it “may not be the definitive treatment for the athletes' knee, as further procedures may be indicated in the future,” said Dr. Gobbi, an orthopedic surgeon with the Orthopedic Arthroscopic Surgery International Research Center in Milan. “However, it can relieve symptoms and delay the need for further treatment.”

Dr. Gobbi and his associate Dr. Ramces Francisco followed 53 professional and recreational athletes who underwent microfracture surgery for unilateral knee articular cartilage injury at their center. Mean patient age was 38 years. Of the patients, 33 were male, and 26 were professional athletes. Mean follow-up was 6 years.

Outcomes were assessed using the Lysholm score, Tegner activity level score, the International Knee Documentation Committee (IKDC) scoring system, and a subjective evaluation based on a 100-point scale. Roentgenograms, MRI, or CT scans were done pre- and postoperatively.

Dr. Gobbi reported that the cause of most injuries was related to sports microtrauma (38%) and macrotrauma (21%), although 38% of patients did not report any traumatic etiology and 4% showed patellar malalignment. The most common location of injury was the medial femoral condyle (61%), and the mean defect size among study participants was 4 cm

Between baseline and final follow-up the mean Lysholm scores improved from 57 to 87; the Tegner scores improved from 3 to 5; and the subjective evaluation improved from 40/100 to 70/100. At baseline, only three patients scored an A or B on the IKDC, but by final follow-up, 70% of patients scored an A or B.

Also by final follow-up, activities of daily living improved in 65% of patients while imaging studies revealed increased degenerative changes in 30% of patients.

“When we analyzed the [return to] strenuous sports activities, we found they increased to 80% in the first 2 years but then gradually decreased to 55% at final follow-up,” Dr. Gobbi added. Changing to a low-risk sport, advancing age of the study participants, work and family obligations, and the influence of degenerative joint disease may have contributed to the decline in postsurgical sports activity.

Second-look arthroscopy performed in 10 patients showed that the articular defects were covered with fibrocartilaginous tissue at a level adjacent with normal articular surface and were firm when palpated with a probe. Biopsies from these same 10 patients showed areas of fibromyxoid tissue with differentiation, a transition zone with cartilage tissue, and initial hyaline transformation tissue.

Candidates should be evaluated by age, activity level, type of sport, type of injury, expectations, associated pathologies, likelihood of rehabilitation compliance, and the articular depth of the defect.

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. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also 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. Seventy-five percent of the subjects on 240 mg a day of febuxostat 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, Dr. Schumacher 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, added Dr. Schumacher, who reported receiving 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. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also 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. Seventy-five percent of the subjects on 240 mg a day of febuxostat 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, Dr. Schumacher 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, added Dr. Schumacher, who reported receiving 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. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also 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. Seventy-five percent of the subjects on 240 mg a day of febuxostat 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, Dr. Schumacher 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, added Dr. Schumacher, who reported receiving funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but long-term safety data are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was very small, so this finding remains “difficult to interpret,” the researchers noted.

The use of ulcer-healing drugs such as proton pump inhibitors reduced the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, they added.

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but long-term safety data are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was very small, so this finding remains “difficult to interpret,” the researchers noted.

The use of ulcer-healing drugs such as proton pump inhibitors reduced the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, they added.

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but long-term safety data are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was very small, so this finding remains “difficult to interpret,” the researchers noted.

The use of ulcer-healing drugs such as proton pump inhibitors reduced the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, they added.

SAN DIEGO — A second or third course of treatment with rituximab was safe and effective in patients with active rheumatoid arthritis enrolled in an open-label extension study, according to two poster presentations at the annual meeting of the American College of Rheumatology.

The monoclonal antibody rituximab had previously been investigated in two phase II studies in rheumatoid arthritis, and patients who had demonstrated improvement in the first treatment course (C1) were eligible to enroll in the extension phase.

Thus far 192 have enrolled; 141 have received a second course (C2) of rituximab treatment, and 25 received a third course (C3), according to Dr. Paul Emery of the Leeds (England) General Infirmary.

During C1, patients received intravenous rituximab in a dosage of 500 mg or 1,000 mg on days 1 and 15, along with methotrexate, cyclophosphamide, or no disease-modifying antirheumatic drug. They also received corticosteroids or placebo.

During C2, patients received 1,000-mg rituximab on days 1 and 15, 10–25 mg/week of methotrexate, and intravenous glucocorticoid premedication; they also received oral glucocorticoids for two weeks. Responses at week 24 were compared with the C1 and C2 baselines.

In the poster that summarized the safety data from C2, Dr. Emery reported that the percentage of patients who experienced serious adverse events after C2 was similar to that after C1 (11% and 10%, respectively).

There was no evidence of cumulative toxicity with repeat courses of the drug, he noted.

Following C1, there was one serious infection (bacterial arthritis). Four patients experienced serious infections following C2—one each of appendicitis, otitis media, bronchopneumonia, and urinary tract infection.

There have been no reports of serious infections following C3, wrote Dr. Emery.

The majority of infusion-related adverse events were mild to moderate.

A separate poster presented efficacy data from the first 78 patients who have either been followed for 24 weeks following C2 or who withdrew from the trial.

“By all measures, rituximab retreatment following C2 was effective,” wrote Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas.

Disease Activity Score (DAS)-28 fell from a mean of 6.95 at C1 baseline to 4.58 at week 24, and then from a mean of 6.43 at C2 baseline to 4.16.

A total of 47 patients achieved ACR20 responses from the C2 baseline, and 57 achieved good to moderate EULAR responses.

C-reactive protein levels and rheumatoid factor titers both were significantly reduced during the observation periods after C1 and C2.

Rituximab targets CD20-positive B cells, and by binding CD20 it depletes B cells. However, because CD20 is not expressed on stem or plasma cells, B-cell recovery subsequently occurs.

Both B-cell depleted and B-cell recovered patients responded following C2, Dr. Fleischmann wrote.

Dr. Fleischmann disclosed that he has received research grants and consulting fees and is on the speakers' bureau of Genentech Inc.

Dr. Emery disclosed that he has received research grants and consulting fees from Roche.

There was no evidence of cumulative toxicity with repeated courses of rituximab. DR. EMERY

SAN DIEGO — A second or third course of treatment with rituximab was safe and effective in patients with active rheumatoid arthritis enrolled in an open-label extension study, according to two poster presentations at the annual meeting of the American College of Rheumatology.

The monoclonal antibody rituximab had previously been investigated in two phase II studies in rheumatoid arthritis, and patients who had demonstrated improvement in the first treatment course (C1) were eligible to enroll in the extension phase.

Thus far 192 have enrolled; 141 have received a second course (C2) of rituximab treatment, and 25 received a third course (C3), according to Dr. Paul Emery of the Leeds (England) General Infirmary.

During C1, patients received intravenous rituximab in a dosage of 500 mg or 1,000 mg on days 1 and 15, along with methotrexate, cyclophosphamide, or no disease-modifying antirheumatic drug. They also received corticosteroids or placebo.

During C2, patients received 1,000-mg rituximab on days 1 and 15, 10–25 mg/week of methotrexate, and intravenous glucocorticoid premedication; they also received oral glucocorticoids for two weeks. Responses at week 24 were compared with the C1 and C2 baselines.

In the poster that summarized the safety data from C2, Dr. Emery reported that the percentage of patients who experienced serious adverse events after C2 was similar to that after C1 (11% and 10%, respectively).

There was no evidence of cumulative toxicity with repeat courses of the drug, he noted.

Following C1, there was one serious infection (bacterial arthritis). Four patients experienced serious infections following C2—one each of appendicitis, otitis media, bronchopneumonia, and urinary tract infection.

There have been no reports of serious infections following C3, wrote Dr. Emery.

The majority of infusion-related adverse events were mild to moderate.

A separate poster presented efficacy data from the first 78 patients who have either been followed for 24 weeks following C2 or who withdrew from the trial.

“By all measures, rituximab retreatment following C2 was effective,” wrote Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas.

Disease Activity Score (DAS)-28 fell from a mean of 6.95 at C1 baseline to 4.58 at week 24, and then from a mean of 6.43 at C2 baseline to 4.16.

A total of 47 patients achieved ACR20 responses from the C2 baseline, and 57 achieved good to moderate EULAR responses.

C-reactive protein levels and rheumatoid factor titers both were significantly reduced during the observation periods after C1 and C2.

Rituximab targets CD20-positive B cells, and by binding CD20 it depletes B cells. However, because CD20 is not expressed on stem or plasma cells, B-cell recovery subsequently occurs.

Both B-cell depleted and B-cell recovered patients responded following C2, Dr. Fleischmann wrote.

Dr. Fleischmann disclosed that he has received research grants and consulting fees and is on the speakers' bureau of Genentech Inc.

Dr. Emery disclosed that he has received research grants and consulting fees from Roche.

There was no evidence of cumulative toxicity with repeated courses of rituximab. DR. EMERY

SAN DIEGO — A second or third course of treatment with rituximab was safe and effective in patients with active rheumatoid arthritis enrolled in an open-label extension study, according to two poster presentations at the annual meeting of the American College of Rheumatology.

The monoclonal antibody rituximab had previously been investigated in two phase II studies in rheumatoid arthritis, and patients who had demonstrated improvement in the first treatment course (C1) were eligible to enroll in the extension phase.

Thus far 192 have enrolled; 141 have received a second course (C2) of rituximab treatment, and 25 received a third course (C3), according to Dr. Paul Emery of the Leeds (England) General Infirmary.

During C1, patients received intravenous rituximab in a dosage of 500 mg or 1,000 mg on days 1 and 15, along with methotrexate, cyclophosphamide, or no disease-modifying antirheumatic drug. They also received corticosteroids or placebo.

During C2, patients received 1,000-mg rituximab on days 1 and 15, 10–25 mg/week of methotrexate, and intravenous glucocorticoid premedication; they also received oral glucocorticoids for two weeks. Responses at week 24 were compared with the C1 and C2 baselines.

In the poster that summarized the safety data from C2, Dr. Emery reported that the percentage of patients who experienced serious adverse events after C2 was similar to that after C1 (11% and 10%, respectively).

There was no evidence of cumulative toxicity with repeat courses of the drug, he noted.

Following C1, there was one serious infection (bacterial arthritis). Four patients experienced serious infections following C2—one each of appendicitis, otitis media, bronchopneumonia, and urinary tract infection.

There have been no reports of serious infections following C3, wrote Dr. Emery.

The majority of infusion-related adverse events were mild to moderate.

A separate poster presented efficacy data from the first 78 patients who have either been followed for 24 weeks following C2 or who withdrew from the trial.

“By all measures, rituximab retreatment following C2 was effective,” wrote Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas.

Disease Activity Score (DAS)-28 fell from a mean of 6.95 at C1 baseline to 4.58 at week 24, and then from a mean of 6.43 at C2 baseline to 4.16.

A total of 47 patients achieved ACR20 responses from the C2 baseline, and 57 achieved good to moderate EULAR responses.

C-reactive protein levels and rheumatoid factor titers both were significantly reduced during the observation periods after C1 and C2.

Rituximab targets CD20-positive B cells, and by binding CD20 it depletes B cells. However, because CD20 is not expressed on stem or plasma cells, B-cell recovery subsequently occurs.

Both B-cell depleted and B-cell recovered patients responded following C2, Dr. Fleischmann wrote.

Dr. Fleischmann disclosed that he has received research grants and consulting fees and is on the speakers' bureau of Genentech Inc.

Dr. Emery disclosed that he has received research grants and consulting fees from Roche.

There was no evidence of cumulative toxicity with repeated courses of rituximab. DR. EMERY

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm.

In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the DMARDs until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% of the patients were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, approximately 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups.

But by the end of the second year patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in two patient subsets: those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery.

Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm.

In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the DMARDs until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% of the patients were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, approximately 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups.

But by the end of the second year patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in two patient subsets: those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery.

Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

SAN DIEGO — Patients in the Utrecht Rheumatoid Arthritis Cohort who began treatment early in the course of disease were less likely to need joint surgery later on, Dr. Suzan M.M. Verstappen said at the annual meeting of the American College of Rheumatology.

In the ongoing Utrecht cohort study, begun in 1990, patients initially were randomized to early treatment with methotrexate, intramuscular gold, or hydroxychloroquine—or to a “pyramid” treatment approach, which was at that time the traditional paradigm.

In the pyramid strategy patients first take aspirin and other NSAIDs, delaying treatment with the DMARDs until later in the course of disease.

At the time of the first analysis, in 1994, it was apparent that patients in the early DMARD group were faring better, and henceforth, all patients were randomized to one of the three drugs, she said.

“In the present study we investigated the prevalence of joint surgery and looked at which clinical, radiographic, and demographic variables in the first 2 years of treatment—when we all know a lot of disease activity occurs—predicted later joint surgery,” said Dr. Verstappen of University Medical Center Utrecht (the Netherlands).

The cohort included 482 patients, whose mean age was 56 years and mean disease duration was 7.2 years. A total of 70% of the patients were female, and 65% were rheumatoid factor positive.

Overall, 144 patients underwent a total of 256 surgeries. Of these interventions, 32% were major surgeries such as total joint replacement, 50% were intermediate procedures such as arthrodesis, and 18% were minor interventions such as arthroscopy.

By the end of the fifth year, approximately 18% of patients had required at least one type of surgical intervention, according to Kaplan-Meier survival analysis. Overall mean survival time until surgery was 10 years, and for the major surgical interventions, the mean survival time was 12 years.

With regard to the need for surgical intervention among patients who responded to drug therapy, compared with those who were nonresponders, at the end of the first year no significant difference was seen between the two groups.

But by the end of the second year patients who responded to drug therapy had fewer surgical interventions, she said.

Furthermore, surgical interventions were significantly more common in two patient subsets: those whose functional disability was worse at baseline and those who initially were randomized to NSAID therapy.

Multivariate Cox regression analyses of the 1-year data found that female gender, delayed start with DMARDs, and radiographic progression were predictive of later surgery.

Hazard ratios for these variables were 1.55, 1.68, and 1.016, respectively, Dr. Verstappen said.

At the end of the second year, only a delayed start of DMARD therapy and radiographic progression were predictors, with hazard ratios of 1.73 and 1.029, respectively, on the multivariate analysis.

The need for joint surgery can be considered an outcome measure reflecting an unfavorable course of rheumatoid arthritis, and a significant number of patients still require some type of surgical intervention, Dr. Verstappen said.

“This is the first study to demonstrate that early treatment prevents later surgical intervention, and we hope that with more early aggressive treatment the percentage of patients requiring surgery later on will decrease further,” she said.

HONOLULU — A novel fixed-combination tablet comprising an immediate-release proton pump inhibitor plus an enteric-coated NSAID showed considerable promise for the prevention of upper GI mucosal injury in a pilot study, Dr. W. James Alexander reported at the annual meeting of the American College of Gastroenterology.

Large clinical trials are now being planned to evaluate the efficacy of the fixed-combination drug, which is designed to ensure adherence to gastroprotective therapy when recommended for NSAID users, explained Dr. Alexander, senior vice president of product development and chief medical officer at Pozen Inc., Chapel Hill, N.C.

Pozen has been issued a patent for the fixed-combination tablet, known for now as PN 100.

Each tablet contains 15 mg of immediate-release lansoprazole surrounding a core of 500 mg of naproxen, which has a pH-sensitive enteric coating.

Dr. Alexander reported on 60 healthy volunteers randomized to 14 days of one of three treatment regimens: PN 100, twice daily; 500 mg of enteric-coated naproxen, twice daily; or 15 mg of delayed-release lansoprazole in the morning plus naproxen 500 mg, twice daily, which is the type of gastroprotective regimen most often used in current clinical practice.

Endoscopy performed on day 14 by a gastroenterologist blinded to treatment status revealed 5 subjects in the PN 100 group had Lanza grade 3 or 4 mucosal lesions, compared with 15 subjects on twice-daily enteric naproxen and 14 on delayed-release lansoprazole plus naproxen twice daily. Two patients on enteric naproxen developed gastric ulcers, as did one on delayed-release lansoprazole plus naproxen. None of the PN 100-treated subjects developed gastric ulcers.

The mean cumulative number of erosions found at endoscopy on days 8 and 14 was 10 in the PN 100 group, 26 with enteric naproxen alone, and 19 with delayed-release lansoprazole plus naproxen.

Findings from 24-hour gastric acid pH monitoring indicated nocturnal acid suppression was better in patients taking twice-daily PN 100 than in those using the once-daily delayed-release lansoprazole preparation plus twice-daily naproxen.

Large clinical trials are being planned to evaluate the combo agent's efficacy. DR. ALEXANDER

HONOLULU — A novel fixed-combination tablet comprising an immediate-release proton pump inhibitor plus an enteric-coated NSAID showed considerable promise for the prevention of upper GI mucosal injury in a pilot study, Dr. W. James Alexander reported at the annual meeting of the American College of Gastroenterology.

Large clinical trials are now being planned to evaluate the efficacy of the fixed-combination drug, which is designed to ensure adherence to gastroprotective therapy when recommended for NSAID users, explained Dr. Alexander, senior vice president of product development and chief medical officer at Pozen Inc., Chapel Hill, N.C.

Pozen has been issued a patent for the fixed-combination tablet, known for now as PN 100.

Each tablet contains 15 mg of immediate-release lansoprazole surrounding a core of 500 mg of naproxen, which has a pH-sensitive enteric coating.

Dr. Alexander reported on 60 healthy volunteers randomized to 14 days of one of three treatment regimens: PN 100, twice daily; 500 mg of enteric-coated naproxen, twice daily; or 15 mg of delayed-release lansoprazole in the morning plus naproxen 500 mg, twice daily, which is the type of gastroprotective regimen most often used in current clinical practice.

Endoscopy performed on day 14 by a gastroenterologist blinded to treatment status revealed 5 subjects in the PN 100 group had Lanza grade 3 or 4 mucosal lesions, compared with 15 subjects on twice-daily enteric naproxen and 14 on delayed-release lansoprazole plus naproxen twice daily. Two patients on enteric naproxen developed gastric ulcers, as did one on delayed-release lansoprazole plus naproxen. None of the PN 100-treated subjects developed gastric ulcers.

The mean cumulative number of erosions found at endoscopy on days 8 and 14 was 10 in the PN 100 group, 26 with enteric naproxen alone, and 19 with delayed-release lansoprazole plus naproxen.

Findings from 24-hour gastric acid pH monitoring indicated nocturnal acid suppression was better in patients taking twice-daily PN 100 than in those using the once-daily delayed-release lansoprazole preparation plus twice-daily naproxen.

Large clinical trials are being planned to evaluate the combo agent's efficacy. DR. ALEXANDER

HONOLULU — A novel fixed-combination tablet comprising an immediate-release proton pump inhibitor plus an enteric-coated NSAID showed considerable promise for the prevention of upper GI mucosal injury in a pilot study, Dr. W. James Alexander reported at the annual meeting of the American College of Gastroenterology.

Large clinical trials are now being planned to evaluate the efficacy of the fixed-combination drug, which is designed to ensure adherence to gastroprotective therapy when recommended for NSAID users, explained Dr. Alexander, senior vice president of product development and chief medical officer at Pozen Inc., Chapel Hill, N.C.

Pozen has been issued a patent for the fixed-combination tablet, known for now as PN 100.

Each tablet contains 15 mg of immediate-release lansoprazole surrounding a core of 500 mg of naproxen, which has a pH-sensitive enteric coating.

Dr. Alexander reported on 60 healthy volunteers randomized to 14 days of one of three treatment regimens: PN 100, twice daily; 500 mg of enteric-coated naproxen, twice daily; or 15 mg of delayed-release lansoprazole in the morning plus naproxen 500 mg, twice daily, which is the type of gastroprotective regimen most often used in current clinical practice.

Endoscopy performed on day 14 by a gastroenterologist blinded to treatment status revealed 5 subjects in the PN 100 group had Lanza grade 3 or 4 mucosal lesions, compared with 15 subjects on twice-daily enteric naproxen and 14 on delayed-release lansoprazole plus naproxen twice daily. Two patients on enteric naproxen developed gastric ulcers, as did one on delayed-release lansoprazole plus naproxen. None of the PN 100-treated subjects developed gastric ulcers.

The mean cumulative number of erosions found at endoscopy on days 8 and 14 was 10 in the PN 100 group, 26 with enteric naproxen alone, and 19 with delayed-release lansoprazole plus naproxen.

Findings from 24-hour gastric acid pH monitoring indicated nocturnal acid suppression was better in patients taking twice-daily PN 100 than in those using the once-daily delayed-release lansoprazole preparation plus twice-daily naproxen.

Large clinical trials are being planned to evaluate the combo agent's efficacy. DR. ALEXANDER