Rheumatoid Arthritis

TUCSON, ARIZ. — Gelfoam interposition is an effective, tendon-sparing alternative to the anchovy procedure for the treatment of trapeziometacarpal osteoarthritis, Dr. Ronald E. Palmer said at the annual meeting of the American Association for Hand Surgery.

The classic treatment for osteoarthritis of the trapezial metacarpal includes excision of the arthritic trapezium bone, with a ligament reconstruction using a forearm tendon, typically the flexor carpi radialis tendon. The remainder of the tendon is then rolled up like an anchovy filet when packaged in a can for sale and interposed in place of the trapezium, where it serves as a biological cushion and minimizes collapse.

Gelfoam interposition “is an effective procedure that is much easier to do” than the anchovy procedure, said Dr. Palmer of the Orthopedic Institute of Illinois in Peoria.

“It has few of the complications that the other procedures have—certainly no synovitis or osteolysis—and it spares the use of other tendons that may cause problems.” Dr. Palmer began using Gelfoam in 1996 and has now performed interpositions in 139 patients with symptomatic osteoarthritis of the trapezial metacarpal, Eaton classification stages II-IV.

All patients were evaluated with a clinical examination and questionnaire an average of 2 months after the procedure, said Dr. Palmer.

Pain relief was achieved in all cases, and all patients were satisfied with their postoperative results, he said, citing improved function and strength as measured by thumb carpal-metacarpal extension and abduction, thumb opposition, grip strength, pinch tip, palmar pinch, and lateral pinch.

The first web space did not atrophy after the procedure. There were no complications or morbidity.

Dr. Palmer said the anchovy procedure provides excellent pain relief.

But in his experience, there frequently wasn't enough tendon left with the anchovy procedure to adequately fill the space left by the excised trapezium.

TUCSON, ARIZ. — Gelfoam interposition is an effective, tendon-sparing alternative to the anchovy procedure for the treatment of trapeziometacarpal osteoarthritis, Dr. Ronald E. Palmer said at the annual meeting of the American Association for Hand Surgery.

The classic treatment for osteoarthritis of the trapezial metacarpal includes excision of the arthritic trapezium bone, with a ligament reconstruction using a forearm tendon, typically the flexor carpi radialis tendon. The remainder of the tendon is then rolled up like an anchovy filet when packaged in a can for sale and interposed in place of the trapezium, where it serves as a biological cushion and minimizes collapse.

Gelfoam interposition “is an effective procedure that is much easier to do” than the anchovy procedure, said Dr. Palmer of the Orthopedic Institute of Illinois in Peoria.

“It has few of the complications that the other procedures have—certainly no synovitis or osteolysis—and it spares the use of other tendons that may cause problems.” Dr. Palmer began using Gelfoam in 1996 and has now performed interpositions in 139 patients with symptomatic osteoarthritis of the trapezial metacarpal, Eaton classification stages II-IV.

All patients were evaluated with a clinical examination and questionnaire an average of 2 months after the procedure, said Dr. Palmer.

Pain relief was achieved in all cases, and all patients were satisfied with their postoperative results, he said, citing improved function and strength as measured by thumb carpal-metacarpal extension and abduction, thumb opposition, grip strength, pinch tip, palmar pinch, and lateral pinch.

The first web space did not atrophy after the procedure. There were no complications or morbidity.

Dr. Palmer said the anchovy procedure provides excellent pain relief.

But in his experience, there frequently wasn't enough tendon left with the anchovy procedure to adequately fill the space left by the excised trapezium.

TUCSON, ARIZ. — Gelfoam interposition is an effective, tendon-sparing alternative to the anchovy procedure for the treatment of trapeziometacarpal osteoarthritis, Dr. Ronald E. Palmer said at the annual meeting of the American Association for Hand Surgery.

The classic treatment for osteoarthritis of the trapezial metacarpal includes excision of the arthritic trapezium bone, with a ligament reconstruction using a forearm tendon, typically the flexor carpi radialis tendon. The remainder of the tendon is then rolled up like an anchovy filet when packaged in a can for sale and interposed in place of the trapezium, where it serves as a biological cushion and minimizes collapse.

Gelfoam interposition “is an effective procedure that is much easier to do” than the anchovy procedure, said Dr. Palmer of the Orthopedic Institute of Illinois in Peoria.

“It has few of the complications that the other procedures have—certainly no synovitis or osteolysis—and it spares the use of other tendons that may cause problems.” Dr. Palmer began using Gelfoam in 1996 and has now performed interpositions in 139 patients with symptomatic osteoarthritis of the trapezial metacarpal, Eaton classification stages II-IV.

All patients were evaluated with a clinical examination and questionnaire an average of 2 months after the procedure, said Dr. Palmer.

Pain relief was achieved in all cases, and all patients were satisfied with their postoperative results, he said, citing improved function and strength as measured by thumb carpal-metacarpal extension and abduction, thumb opposition, grip strength, pinch tip, palmar pinch, and lateral pinch.

The first web space did not atrophy after the procedure. There were no complications or morbidity.

Dr. Palmer said the anchovy procedure provides excellent pain relief.

But in his experience, there frequently wasn't enough tendon left with the anchovy procedure to adequately fill the space left by the excised trapezium.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

SNOWMASS, COLO. — Only the absence of “trio” families prevents major breakthroughs in finding genetic mutations for rheumatoid arthritis, even using the present technology, said Dr. Peter K. Gregersen at a symposium sponsored by the American College of Rheumatology.

Trio families, consisting of the patient and both parents, “are very hard to find, because RA is a late-onset disease,” explained Dr. Gregersen, the principal investigator of the North American Rheumatoid Arthritis Consortium, the world's largest effort to identify the genes associated with the development of rheumatoid arthritis. “But [studying trio families] is an extremely powerful way of doing association mapping.”

In searching for genes associated with complex diseases such as rheumatoid arthritis, the approach is to survey the entire genome of many individuals and their siblings with single nucleotide polymorphism markers (SNPs) to find regions of the DNA where particular SNPs are shared more frequently among affected siblings than nonaffected siblings.

This process requires enormous numbers of individuals, especially since rates of RA vary among different populations. Dr. Gergersen's consortium currently has about 1,000 sibling pairs, representing almost 800 families and 200 trio families. It has taken a few years to recruit them, and he estimates that they will need “several thousand,” said Dr. Gregersen, of North Shore University Hospital, Manhasset, N.Y.

Once the shared SNPs are found, the researchers can plot those SNP regions on the human genome map to try to identify likely candidate genes and refine the search.

A gene found by Dr. Gregersen's group with this method is the PTPN22 allele. The gene encodes a tyrosine phosphatase inhibitory to T cells, and it appears also to be involved in Graves' disease, systemic lupus, and type 1 diabetes.

Just in the last couple of years, the technology for this kind of work has all come together: the human genome map, the catalog of SNPs, and a fiber-optic technology for rapidly sorting through SNPs. And the cost of genotyping has dropped dramatically, from about $1 per SNP to “a couple of pennies,” Dr. Gregersen said.

But much more work needs to be done to hunt out other candidate genes. Neither the HLA-DRB1 allele, identified back in the 1970s, nor the PTPN22 allele accounts for all of the relative risk for rheumatoid arthritis, which has a heritability of about 60%.

The PTPN22 polymorphism is found in 28% of rheumatoid arthritis patients, versus 17% of the general population.

More than 300 other possible candidate gene regions have been identified already, and others probably exist.

But the sheer volume of the material that needs to be sorted through for this work means that even when the probability of chance associations is extremely low, they will occur often, Dr. Gregersen said.

The use of trio families, where the genotype of an affected individual can be compared with a parent who would have transferred the DNA of interest with the parent who did not, can greatly speed and improve the process.

The work will also elucidate the pharmacogenetics of response to arthritis drugs, an area of research about which there has been a lot of talk, but not much clinical translation so far, Dr. Gregersen said.

Physicians who have an adult patient with a confirmed diagnosis of RA, two living parents, and an interest in participating should have the patient call 800-382-4827.

The rheumatologists who assist are compensated $150 for their time for each patient. They need to confirm the subject's RA diagnosis on a checklist, and draw a blood specimen for overnight delivery. They will also be paid an additional $50 for each blood sample they draw from a parent. For parents not local to the rheumatologist, a phlebotomy service is available, arranged and paid for by the consortium.

Hip OA Injections Have Limited Effect

Intraarticular corticosteroid injections into the hip joints of osteoarthritis patients provide significant temporary pain relief, but do not provide long-term relief, according to a new study.

“I believe that the important message is that you cannot use this for standard therapy,” Dr. Henning Bliddal, a coauthor of the study, said in an interview.

Researchers at the Parker Institute at Frederiksberg (Denmark) Hospital tested pain relief among 101 patients with hip osteoarthritis randomized into three groups. The researchers wrote that to their knowledge, it is the first randomized, placebo-controlled trial of hyaluronic acid injections in the hip joint (Osteoarthritis Cartilage 2006;14:163–70).

Each patient underwent three injections at 14-day intervals. Patients receiving hyaluronic acid were given three injections of the medication. Those receiving corticosteroids were given a single injection of the medication followed by two sham injections. Those receiving a placebo received injections of saline water.

Researchers' primary outcome was “pain on walking,” using the patients' self-assessment on the 100-mm visual analog scale, measured at baseline, 14 days, 28 days, and 90 days.

The mean reduction in “pain on walking” for patients receiving corticosteroid injections was 12 points on the visual analog scale at 14 days, 15 points at 28 days, and 9 points at 90 days. The difference at 90 days was not considered statistically significant.

For those patients receiving the hyaluronic acid injection, the “pain on walking” measurement on the visual analog scale was reduced a mean of 10 points at 14 days, 11 points at 28 days, and 11 points at 90 days.

Assess Knee Replacement Expectations

Clinicians should assess osteoarthritis patients' understanding of total knee replacement before ordering the procedure, because their perceptions about the surgery may cloud the decision process, according to Dr. Francine M. Toye of Nuffield Orthopaedic Centre, Oxford, England, and her associates.

To explore patient beliefs, Dr. Toye and her associates conducted lengthy interviews with 18 patients awaiting total knee replacement (TKR) at a single British orthopedic hospital. The 12 men (aged 54–77 years) and 6 women (aged 60–76 years) had scored lower than average for both knee pain and loss of function on a standard assessment tool, indicating that they fell “below a certain threshold of clinical need” for the procedure.

Although their symptom burden was low, all patients believed that a specific medical diagnosis (osteoarthritis) confirmed by x-ray findings made TKR a virtual necessity. All patients also reported that their physicians compelled the surgery, not by means of coercion but simply because their “expert” opinion prevailed.

All but a few patients believed their osteoarthritis would inevitably progress, and they thought they would become “crippled” or “totally immobile” if they didn't undergo TKR quickly. They reported that health care professionals reinforced this belief in many instances, even though it was clearly erroneous, the researchers said (Soc. Sci. Med. 2005; doi:10.1016/j.socscimed.2005.11.054).

Most patients viewed TKR as the “only cure” for knee osteoarthritis. Most didn't expect a 100% improvement, but still many patients, particularly men, reported that they thought they would be “back to normal” after the procedure.

Adalimumab Aids All Psoriatic Arthritis

Adalimumab is effective in treating both mild to severe skin disease in patients with psoriatic arthritis, Dr. Dafna D. Gladman reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

To assess whether the level of skin disease affected the response of psoriasis to the drug, Dr. Gladman and her associates performed a posthoc analysis of a 24-week, placebo-controlled phase III trial of patients with moderately active to severely active psoriatic arthritis.

Among those in the adalimumab-treated group, 53 patients had mild to moderate skin disease, with a Psoriasis Area and Severity Index (PASI) score of less than 10 at baseline. Sixteen patients had moderate to severe skin disease, with a PASI score of 10 or more.

PASI responses occurred quickly and were maintained. After 24 weeks of drug treatment, the two subgroups had similar response rates. Comparing the mild-moderate and moderate-severe groups, a PASI 50 score (a 50% reduction from baseline) was achieved by 39 (74%) and 13 (81%), respectively; a PASI 90 score was achieved by 23 (43%) and 6 (38%) in the respective groups, reported Dr. Gladman of the University of Toronto. Dr. Gladman is a primary investigator for Abbott Laboratories, which makes adalimumab (Humira).

Hip OA Injections Have Limited Effect

Intraarticular corticosteroid injections into the hip joints of osteoarthritis patients provide significant temporary pain relief, but do not provide long-term relief, according to a new study.

“I believe that the important message is that you cannot use this for standard therapy,” Dr. Henning Bliddal, a coauthor of the study, said in an interview.

Researchers at the Parker Institute at Frederiksberg (Denmark) Hospital tested pain relief among 101 patients with hip osteoarthritis randomized into three groups. The researchers wrote that to their knowledge, it is the first randomized, placebo-controlled trial of hyaluronic acid injections in the hip joint (Osteoarthritis Cartilage 2006;14:163–70).

Each patient underwent three injections at 14-day intervals. Patients receiving hyaluronic acid were given three injections of the medication. Those receiving corticosteroids were given a single injection of the medication followed by two sham injections. Those receiving a placebo received injections of saline water.

Researchers' primary outcome was “pain on walking,” using the patients' self-assessment on the 100-mm visual analog scale, measured at baseline, 14 days, 28 days, and 90 days.

The mean reduction in “pain on walking” for patients receiving corticosteroid injections was 12 points on the visual analog scale at 14 days, 15 points at 28 days, and 9 points at 90 days. The difference at 90 days was not considered statistically significant.

For those patients receiving the hyaluronic acid injection, the “pain on walking” measurement on the visual analog scale was reduced a mean of 10 points at 14 days, 11 points at 28 days, and 11 points at 90 days.

Assess Knee Replacement Expectations

Clinicians should assess osteoarthritis patients' understanding of total knee replacement before ordering the procedure, because their perceptions about the surgery may cloud the decision process, according to Dr. Francine M. Toye of Nuffield Orthopaedic Centre, Oxford, England, and her associates.

To explore patient beliefs, Dr. Toye and her associates conducted lengthy interviews with 18 patients awaiting total knee replacement (TKR) at a single British orthopedic hospital. The 12 men (aged 54–77 years) and 6 women (aged 60–76 years) had scored lower than average for both knee pain and loss of function on a standard assessment tool, indicating that they fell “below a certain threshold of clinical need” for the procedure.

Although their symptom burden was low, all patients believed that a specific medical diagnosis (osteoarthritis) confirmed by x-ray findings made TKR a virtual necessity. All patients also reported that their physicians compelled the surgery, not by means of coercion but simply because their “expert” opinion prevailed.

All but a few patients believed their osteoarthritis would inevitably progress, and they thought they would become “crippled” or “totally immobile” if they didn't undergo TKR quickly. They reported that health care professionals reinforced this belief in many instances, even though it was clearly erroneous, the researchers said (Soc. Sci. Med. 2005; doi:10.1016/j.socscimed.2005.11.054).

Most patients viewed TKR as the “only cure” for knee osteoarthritis. Most didn't expect a 100% improvement, but still many patients, particularly men, reported that they thought they would be “back to normal” after the procedure.

Adalimumab Aids All Psoriatic Arthritis

Adalimumab is effective in treating both mild to severe skin disease in patients with psoriatic arthritis, Dr. Dafna D. Gladman reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

To assess whether the level of skin disease affected the response of psoriasis to the drug, Dr. Gladman and her associates performed a posthoc analysis of a 24-week, placebo-controlled phase III trial of patients with moderately active to severely active psoriatic arthritis.

Among those in the adalimumab-treated group, 53 patients had mild to moderate skin disease, with a Psoriasis Area and Severity Index (PASI) score of less than 10 at baseline. Sixteen patients had moderate to severe skin disease, with a PASI score of 10 or more.

PASI responses occurred quickly and were maintained. After 24 weeks of drug treatment, the two subgroups had similar response rates. Comparing the mild-moderate and moderate-severe groups, a PASI 50 score (a 50% reduction from baseline) was achieved by 39 (74%) and 13 (81%), respectively; a PASI 90 score was achieved by 23 (43%) and 6 (38%) in the respective groups, reported Dr. Gladman of the University of Toronto. Dr. Gladman is a primary investigator for Abbott Laboratories, which makes adalimumab (Humira).

Hip OA Injections Have Limited Effect

Intraarticular corticosteroid injections into the hip joints of osteoarthritis patients provide significant temporary pain relief, but do not provide long-term relief, according to a new study.

“I believe that the important message is that you cannot use this for standard therapy,” Dr. Henning Bliddal, a coauthor of the study, said in an interview.

Researchers at the Parker Institute at Frederiksberg (Denmark) Hospital tested pain relief among 101 patients with hip osteoarthritis randomized into three groups. The researchers wrote that to their knowledge, it is the first randomized, placebo-controlled trial of hyaluronic acid injections in the hip joint (Osteoarthritis Cartilage 2006;14:163–70).

Each patient underwent three injections at 14-day intervals. Patients receiving hyaluronic acid were given three injections of the medication. Those receiving corticosteroids were given a single injection of the medication followed by two sham injections. Those receiving a placebo received injections of saline water.

Researchers' primary outcome was “pain on walking,” using the patients' self-assessment on the 100-mm visual analog scale, measured at baseline, 14 days, 28 days, and 90 days.

The mean reduction in “pain on walking” for patients receiving corticosteroid injections was 12 points on the visual analog scale at 14 days, 15 points at 28 days, and 9 points at 90 days. The difference at 90 days was not considered statistically significant.

For those patients receiving the hyaluronic acid injection, the “pain on walking” measurement on the visual analog scale was reduced a mean of 10 points at 14 days, 11 points at 28 days, and 11 points at 90 days.

Assess Knee Replacement Expectations

Clinicians should assess osteoarthritis patients' understanding of total knee replacement before ordering the procedure, because their perceptions about the surgery may cloud the decision process, according to Dr. Francine M. Toye of Nuffield Orthopaedic Centre, Oxford, England, and her associates.

To explore patient beliefs, Dr. Toye and her associates conducted lengthy interviews with 18 patients awaiting total knee replacement (TKR) at a single British orthopedic hospital. The 12 men (aged 54–77 years) and 6 women (aged 60–76 years) had scored lower than average for both knee pain and loss of function on a standard assessment tool, indicating that they fell “below a certain threshold of clinical need” for the procedure.

Although their symptom burden was low, all patients believed that a specific medical diagnosis (osteoarthritis) confirmed by x-ray findings made TKR a virtual necessity. All patients also reported that their physicians compelled the surgery, not by means of coercion but simply because their “expert” opinion prevailed.

All but a few patients believed their osteoarthritis would inevitably progress, and they thought they would become “crippled” or “totally immobile” if they didn't undergo TKR quickly. They reported that health care professionals reinforced this belief in many instances, even though it was clearly erroneous, the researchers said (Soc. Sci. Med. 2005; doi:10.1016/j.socscimed.2005.11.054).

Most patients viewed TKR as the “only cure” for knee osteoarthritis. Most didn't expect a 100% improvement, but still many patients, particularly men, reported that they thought they would be “back to normal” after the procedure.

Adalimumab Aids All Psoriatic Arthritis

Adalimumab is effective in treating both mild to severe skin disease in patients with psoriatic arthritis, Dr. Dafna D. Gladman reported in a poster presentation at the annual meeting of the American Academy of Dermatology.

To assess whether the level of skin disease affected the response of psoriasis to the drug, Dr. Gladman and her associates performed a posthoc analysis of a 24-week, placebo-controlled phase III trial of patients with moderately active to severely active psoriatic arthritis.

Among those in the adalimumab-treated group, 53 patients had mild to moderate skin disease, with a Psoriasis Area and Severity Index (PASI) score of less than 10 at baseline. Sixteen patients had moderate to severe skin disease, with a PASI score of 10 or more.

PASI responses occurred quickly and were maintained. After 24 weeks of drug treatment, the two subgroups had similar response rates. Comparing the mild-moderate and moderate-severe groups, a PASI 50 score (a 50% reduction from baseline) was achieved by 39 (74%) and 13 (81%), respectively; a PASI 90 score was achieved by 23 (43%) and 6 (38%) in the respective groups, reported Dr. Gladman of the University of Toronto. Dr. Gladman is a primary investigator for Abbott Laboratories, which makes adalimumab (Humira).

Patients currently taking a glucocorticoid have nearly a fivefold increased risk of developing tuberculosis that is independent of other risk factors.

“Our results suggest that glucocorticoid use is associated with a substantially increased risk of developing tuberculosis and that the risk increases with increasing daily dose,” said Susan S. Jick, Sc.D., of Boston University, and her colleagues.

Although chronic corticosteroid use is common among patients with rheumatic diseases, the number of such patients in the study population was too small to say definitely whether use of corticosteroids specifically for arthritis and other rheumatic diseases was associated with an increased risk for TB.

Low body mass index (BMI), diabetes, current smoking, and obstructive pulmonary disorders were also determined to be important risk factors for tuberculosis in a review of 497 new cases of tuberculosis and 1,966 matched controls during the period 1990–2001 (Arthritis Rheum. 2006;55:19–26).

The researchers based their study on data available from the U.K.-based General Practice Research Database. Patients were included if they had a first-time diagnosis of tuberculosis followed by treatment with at least three different antituberculosis medications and if treatment lasted at least 6 months. As many as four control subjects were matched to each patient based on age, gender, the practice attended, and the patient's index date along with the control's visit to the practice that corresponded in time to the patient's index visit.

Assessment of glucocorticoid use was based on prescription data. Patients were classified as currently exposed if they had received a prescription for any oral glucocorticoid and if the supply had lasted until within 120 days prior to the index date. Recent exposure was defined as use that ended 121–180 days before the index date. All other use more than 180 days prior was considered past use.

The researchers also assessed current exposure to antirheumatic drugs or immunosuppressants and the presence of pulmonary disorders, rheumatic disorders, inflammatory bowel diseases, dermatitis, silicosis, renal failure, gastrectomy, and jejunoileal bypass surgery (diagnosed prior to the index date).

Patients currently using corticosteroids were 4.9 times more likely to develop tuberculosis than were nonusers, even after adjusting for the effects of BMI, smoking, disease-modifying antirheumatic drug use, and history of diabetes and pulmonary disease. The risk for tuberculosis remained elevated (OR 4.3) in patients who had recently stopped using corticosteroids.

First-time users were 3.2 times more likely to get tuberculosis than were never users. Patients with longer-term use, extending over two to nine consecutive prescriptions, saw their risk increase sevenfold.

The effect of corticosteroid use on risk for TB increased with increasing dose. The OR was 2.3 in people taking daily doses of prednisone equivalents less than 7.5 mg daily (physiologic) versus those taking supraphysiologic doses of 7.5 mg or more daily (OR 7.0, based on the highest daily dosage received by current users).

Both the American Thoracic Society and the Centers for Disease Control and Prevention agree that more than 15 mg/day of prednisone or its equivalent administered for 1 month or longer is a risk factor for tuberculosis. In light of this, the researchers evaluated the impact of daily dosage using this cutoff. The adjusted odds ratio was 2.8 for those using less than 15 mg of prednisone equivalents per day, while those using 15 mg of prednisone equivalents per day or more had an adjusted odds ratio of 7.7.

“We found that current smoking was associated with a 60% increased risk of tuberculosis. … Although this effect is relatively low, because smoking is prevalent in this study population 17% of all cases are attributable to smoking compared with only 8% of cases attributable to glucocorticoid use in this population,” the researchers said. Those with a BMI less than 20 kg/m

Prior pulmonary diagnoses were also associated with an increased risk of tuberculosis that was independent of other risk factors. A diagnosis of rheumatic disease and use of antirheumatic agents are purported to be risk factors for tuberculosis as well.

However, the number of patients taking antirheumatic drugs in this analysis was low—only 12 patients were currently exposed. Overall 17 participants (cases and controls) had rheumatoid arthritis, 1 had lupus, 12 had polymyalgia rheumatica, and 7 had arteritis. “Despite the large number of tuberculosis cases in this study, the prevalence of antirheumatic agent use was low … and therefore the independent effects for patients taking antirheumatic agents could not be reliably evaluated,” the researchers said.

In an accompanying editorial, Dr. Loreto Carmona observed that “the truth is that the report says little about the risk of TB in patients with rheumatic disease who are treated with glucocorticoids” (Arthritis Rheum. 2005;55:1–2). Dr. Carmona heads the research unit of the Spanish Foundation of Rheumatology in Madrid. It's unclear how much of the risk of tuberculosis is due to rheumatic diseases—for which corticoids are taken—and how much is due to the glucocorticoids.

Patients currently taking a glucocorticoid have nearly a fivefold increased risk of developing tuberculosis that is independent of other risk factors.

“Our results suggest that glucocorticoid use is associated with a substantially increased risk of developing tuberculosis and that the risk increases with increasing daily dose,” said Susan S. Jick, Sc.D., of Boston University, and her colleagues.

Although chronic corticosteroid use is common among patients with rheumatic diseases, the number of such patients in the study population was too small to say definitely whether use of corticosteroids specifically for arthritis and other rheumatic diseases was associated with an increased risk for TB.

Low body mass index (BMI), diabetes, current smoking, and obstructive pulmonary disorders were also determined to be important risk factors for tuberculosis in a review of 497 new cases of tuberculosis and 1,966 matched controls during the period 1990–2001 (Arthritis Rheum. 2006;55:19–26).

The researchers based their study on data available from the U.K.-based General Practice Research Database. Patients were included if they had a first-time diagnosis of tuberculosis followed by treatment with at least three different antituberculosis medications and if treatment lasted at least 6 months. As many as four control subjects were matched to each patient based on age, gender, the practice attended, and the patient's index date along with the control's visit to the practice that corresponded in time to the patient's index visit.

Assessment of glucocorticoid use was based on prescription data. Patients were classified as currently exposed if they had received a prescription for any oral glucocorticoid and if the supply had lasted until within 120 days prior to the index date. Recent exposure was defined as use that ended 121–180 days before the index date. All other use more than 180 days prior was considered past use.

The researchers also assessed current exposure to antirheumatic drugs or immunosuppressants and the presence of pulmonary disorders, rheumatic disorders, inflammatory bowel diseases, dermatitis, silicosis, renal failure, gastrectomy, and jejunoileal bypass surgery (diagnosed prior to the index date).

Patients currently using corticosteroids were 4.9 times more likely to develop tuberculosis than were nonusers, even after adjusting for the effects of BMI, smoking, disease-modifying antirheumatic drug use, and history of diabetes and pulmonary disease. The risk for tuberculosis remained elevated (OR 4.3) in patients who had recently stopped using corticosteroids.

First-time users were 3.2 times more likely to get tuberculosis than were never users. Patients with longer-term use, extending over two to nine consecutive prescriptions, saw their risk increase sevenfold.

The effect of corticosteroid use on risk for TB increased with increasing dose. The OR was 2.3 in people taking daily doses of prednisone equivalents less than 7.5 mg daily (physiologic) versus those taking supraphysiologic doses of 7.5 mg or more daily (OR 7.0, based on the highest daily dosage received by current users).

Both the American Thoracic Society and the Centers for Disease Control and Prevention agree that more than 15 mg/day of prednisone or its equivalent administered for 1 month or longer is a risk factor for tuberculosis. In light of this, the researchers evaluated the impact of daily dosage using this cutoff. The adjusted odds ratio was 2.8 for those using less than 15 mg of prednisone equivalents per day, while those using 15 mg of prednisone equivalents per day or more had an adjusted odds ratio of 7.7.

“We found that current smoking was associated with a 60% increased risk of tuberculosis. … Although this effect is relatively low, because smoking is prevalent in this study population 17% of all cases are attributable to smoking compared with only 8% of cases attributable to glucocorticoid use in this population,” the researchers said. Those with a BMI less than 20 kg/m

Prior pulmonary diagnoses were also associated with an increased risk of tuberculosis that was independent of other risk factors. A diagnosis of rheumatic disease and use of antirheumatic agents are purported to be risk factors for tuberculosis as well.

However, the number of patients taking antirheumatic drugs in this analysis was low—only 12 patients were currently exposed. Overall 17 participants (cases and controls) had rheumatoid arthritis, 1 had lupus, 12 had polymyalgia rheumatica, and 7 had arteritis. “Despite the large number of tuberculosis cases in this study, the prevalence of antirheumatic agent use was low … and therefore the independent effects for patients taking antirheumatic agents could not be reliably evaluated,” the researchers said.

In an accompanying editorial, Dr. Loreto Carmona observed that “the truth is that the report says little about the risk of TB in patients with rheumatic disease who are treated with glucocorticoids” (Arthritis Rheum. 2005;55:1–2). Dr. Carmona heads the research unit of the Spanish Foundation of Rheumatology in Madrid. It's unclear how much of the risk of tuberculosis is due to rheumatic diseases—for which corticoids are taken—and how much is due to the glucocorticoids.

Patients currently taking a glucocorticoid have nearly a fivefold increased risk of developing tuberculosis that is independent of other risk factors.

“Our results suggest that glucocorticoid use is associated with a substantially increased risk of developing tuberculosis and that the risk increases with increasing daily dose,” said Susan S. Jick, Sc.D., of Boston University, and her colleagues.

Although chronic corticosteroid use is common among patients with rheumatic diseases, the number of such patients in the study population was too small to say definitely whether use of corticosteroids specifically for arthritis and other rheumatic diseases was associated with an increased risk for TB.

Low body mass index (BMI), diabetes, current smoking, and obstructive pulmonary disorders were also determined to be important risk factors for tuberculosis in a review of 497 new cases of tuberculosis and 1,966 matched controls during the period 1990–2001 (Arthritis Rheum. 2006;55:19–26).

The researchers based their study on data available from the U.K.-based General Practice Research Database. Patients were included if they had a first-time diagnosis of tuberculosis followed by treatment with at least three different antituberculosis medications and if treatment lasted at least 6 months. As many as four control subjects were matched to each patient based on age, gender, the practice attended, and the patient's index date along with the control's visit to the practice that corresponded in time to the patient's index visit.

Assessment of glucocorticoid use was based on prescription data. Patients were classified as currently exposed if they had received a prescription for any oral glucocorticoid and if the supply had lasted until within 120 days prior to the index date. Recent exposure was defined as use that ended 121–180 days before the index date. All other use more than 180 days prior was considered past use.

The researchers also assessed current exposure to antirheumatic drugs or immunosuppressants and the presence of pulmonary disorders, rheumatic disorders, inflammatory bowel diseases, dermatitis, silicosis, renal failure, gastrectomy, and jejunoileal bypass surgery (diagnosed prior to the index date).

Patients currently using corticosteroids were 4.9 times more likely to develop tuberculosis than were nonusers, even after adjusting for the effects of BMI, smoking, disease-modifying antirheumatic drug use, and history of diabetes and pulmonary disease. The risk for tuberculosis remained elevated (OR 4.3) in patients who had recently stopped using corticosteroids.

First-time users were 3.2 times more likely to get tuberculosis than were never users. Patients with longer-term use, extending over two to nine consecutive prescriptions, saw their risk increase sevenfold.

The effect of corticosteroid use on risk for TB increased with increasing dose. The OR was 2.3 in people taking daily doses of prednisone equivalents less than 7.5 mg daily (physiologic) versus those taking supraphysiologic doses of 7.5 mg or more daily (OR 7.0, based on the highest daily dosage received by current users).

Both the American Thoracic Society and the Centers for Disease Control and Prevention agree that more than 15 mg/day of prednisone or its equivalent administered for 1 month or longer is a risk factor for tuberculosis. In light of this, the researchers evaluated the impact of daily dosage using this cutoff. The adjusted odds ratio was 2.8 for those using less than 15 mg of prednisone equivalents per day, while those using 15 mg of prednisone equivalents per day or more had an adjusted odds ratio of 7.7.

“We found that current smoking was associated with a 60% increased risk of tuberculosis. … Although this effect is relatively low, because smoking is prevalent in this study population 17% of all cases are attributable to smoking compared with only 8% of cases attributable to glucocorticoid use in this population,” the researchers said. Those with a BMI less than 20 kg/m

Prior pulmonary diagnoses were also associated with an increased risk of tuberculosis that was independent of other risk factors. A diagnosis of rheumatic disease and use of antirheumatic agents are purported to be risk factors for tuberculosis as well.

However, the number of patients taking antirheumatic drugs in this analysis was low—only 12 patients were currently exposed. Overall 17 participants (cases and controls) had rheumatoid arthritis, 1 had lupus, 12 had polymyalgia rheumatica, and 7 had arteritis. “Despite the large number of tuberculosis cases in this study, the prevalence of antirheumatic agent use was low … and therefore the independent effects for patients taking antirheumatic agents could not be reliably evaluated,” the researchers said.

In an accompanying editorial, Dr. Loreto Carmona observed that “the truth is that the report says little about the risk of TB in patients with rheumatic disease who are treated with glucocorticoids” (Arthritis Rheum. 2005;55:1–2). Dr. Carmona heads the research unit of the Spanish Foundation of Rheumatology in Madrid. It's unclear how much of the risk of tuberculosis is due to rheumatic diseases—for which corticoids are taken—and how much is due to the glucocorticoids.

Celecoxib is just as effective as naproxen and diclofenac for treating osteoarthritis, but it causes significantly fewer serious upper gastrointestinal events, compared with the other agents, according to data from a large international study.

The finding “shows conclusively that celecoxib does reduce the risk of upper GI complications, compared to conventional NSAIDs,” the study's lead author, Dr. Gurkirpal Singh, said. “Up until now managed care has been saying there is no evidence in a randomized, clinical trial that celecoxib is better than NSAIDs in reducing GI bleeding. But here it is; these are level 1 data that conclusively prove that.”

However, Dr. Brennan M.R. Spiegel noted that while the difference favoring celecoxib reached statistical significance in the study, the actual difference was a matter of 1 patient per 100 patient-years, which “is a tiny difference that to me is not enough to warrant spending as much money as we do on COX-2 inhibitors,” said Dr. Spiegel, of the division of digestive diseases at the University of California, Los Angeles.

He added that the study is “notable because it's very large, [but] I believed it before that GI events are less common with coxibs than with NSAIDs. I didn't need another study to demonstrate that.”

In a trial called the Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), Dr. Gurkirpal and his associates randomly assigned 13,194 osteoarthritis patients from 39 countries to double-blinded treatment with celecoxib 100 mg b.i.d., celecoxib 200 mg b.i.d., or nonselective NSAID therapy for 12 weeks. The NSAID therapy consisted of diclofenac 50 mg b.i.d. or naproxen 500 mg b.i.d. (Am. J. Med. 2006; 119:255–66).

Patients with a history of two or more episodes of active peptic ulceration were excluded from the study, as were those with gastrointestinal bleeding or recurrent gastric or duodenal ulcers and those with an esophageal, gastric, or duodenal ulcer within a month prior to randomization. Patients with active gastrointestinal disease or any condition that required NSAID therapy were also excluded from the study.

The mean age of study participants was 62 years, 76% were women, and 80% were white, reported Dr. Singh, of the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. The mean duration of osteoarthritis was 8 years.

Instruments used to measure efficacy included the Patient's Assessment of Arthritis Pain-Visual Analog Scale, Patients' Global Assessment of Arthritis, and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Serious GI events were evaluated by two independent committees that were blinded to patient randomization.

The researchers reported that the primary efficacy measures for both doses of celecoxib were equally effective as the NSAIDs in treating osteoarthritis.

There were 37 confirmed upper GI events: 19 in the patients who took the NSAIDs and 18 in the patients who took celecoxib. That translated into a rate of 2.1 per 100 patient-years for patients who took the NSAIDs vs. a rate of 1.0 per 100 patient-years for those who took celecoxib. The difference was statistically significant with a P value of .023.

A key limitation of the study, Dr. Singh said, is the fact that it was not powered to detect differences in terms of cardiovascular adverse events. “So we can't make any conclusion about that,” he said. “We did not see any statistically significant differences [between treatment groups], but at the time the study was designed, [concerns about COX-2 inhibitors and risk of] myocardial infarction were not an issue, so that's not something we followed.”

To tease that information out, he added, “you'd need a larger study over a longer period of time, perhaps in a high-risk population that has had myocardial infarction. I'd probably want to do it for at least 2 years.”

Dr. Spiegel said that the current standard of care for older patients with osteoarthritis has “overtaken” the overall impact of the SUCCESS-1 study findings.

“The reality is that people are moving to adding a proton pump inhibitor to an NSAID when [osteoarthritis] patients exceed the age of 65 or if they're put on aspirin,” he said. “They're not moving to COX-2 inhibitor, and this study doesn't give me any more reason to put someone on a COX-2 inhibitor as opposed to just adding a PPI to an NSAID, which is overall a cheaper thing to do. [That approach] is more relevant because it's cheaper, it's cost effective, and there's no risk of MI as there is with COX-2 inhibitors. In fact, there's less overall dyspepsia in patients who are on an NSAID plus a PPI, compared to [those on] a COX-2 inhibitor.”

Dr. Singh disclosed that he received research support from Searle Pharmaceuticals, Pharmacia, Pfizer, Merck & Co., Boehringer Ingelheim, TAP Pharmaceuticals, Wyeth, Altana Pharma, GlaxoSmithKline, Novartis Pharmaceuticals Corp., and Centocor Inc.

The finding 'shows conclusively that celecoxib does reduce the risk of upper GI complications.' DR. SINGH

Celecoxib is just as effective as naproxen and diclofenac for treating osteoarthritis, but it causes significantly fewer serious upper gastrointestinal events, compared with the other agents, according to data from a large international study.

The finding “shows conclusively that celecoxib does reduce the risk of upper GI complications, compared to conventional NSAIDs,” the study's lead author, Dr. Gurkirpal Singh, said. “Up until now managed care has been saying there is no evidence in a randomized, clinical trial that celecoxib is better than NSAIDs in reducing GI bleeding. But here it is; these are level 1 data that conclusively prove that.”

However, Dr. Brennan M.R. Spiegel noted that while the difference favoring celecoxib reached statistical significance in the study, the actual difference was a matter of 1 patient per 100 patient-years, which “is a tiny difference that to me is not enough to warrant spending as much money as we do on COX-2 inhibitors,” said Dr. Spiegel, of the division of digestive diseases at the University of California, Los Angeles.

He added that the study is “notable because it's very large, [but] I believed it before that GI events are less common with coxibs than with NSAIDs. I didn't need another study to demonstrate that.”

In a trial called the Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), Dr. Gurkirpal and his associates randomly assigned 13,194 osteoarthritis patients from 39 countries to double-blinded treatment with celecoxib 100 mg b.i.d., celecoxib 200 mg b.i.d., or nonselective NSAID therapy for 12 weeks. The NSAID therapy consisted of diclofenac 50 mg b.i.d. or naproxen 500 mg b.i.d. (Am. J. Med. 2006; 119:255–66).

Patients with a history of two or more episodes of active peptic ulceration were excluded from the study, as were those with gastrointestinal bleeding or recurrent gastric or duodenal ulcers and those with an esophageal, gastric, or duodenal ulcer within a month prior to randomization. Patients with active gastrointestinal disease or any condition that required NSAID therapy were also excluded from the study.

The mean age of study participants was 62 years, 76% were women, and 80% were white, reported Dr. Singh, of the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. The mean duration of osteoarthritis was 8 years.

Instruments used to measure efficacy included the Patient's Assessment of Arthritis Pain-Visual Analog Scale, Patients' Global Assessment of Arthritis, and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Serious GI events were evaluated by two independent committees that were blinded to patient randomization.

The researchers reported that the primary efficacy measures for both doses of celecoxib were equally effective as the NSAIDs in treating osteoarthritis.

There were 37 confirmed upper GI events: 19 in the patients who took the NSAIDs and 18 in the patients who took celecoxib. That translated into a rate of 2.1 per 100 patient-years for patients who took the NSAIDs vs. a rate of 1.0 per 100 patient-years for those who took celecoxib. The difference was statistically significant with a P value of .023.

A key limitation of the study, Dr. Singh said, is the fact that it was not powered to detect differences in terms of cardiovascular adverse events. “So we can't make any conclusion about that,” he said. “We did not see any statistically significant differences [between treatment groups], but at the time the study was designed, [concerns about COX-2 inhibitors and risk of] myocardial infarction were not an issue, so that's not something we followed.”

To tease that information out, he added, “you'd need a larger study over a longer period of time, perhaps in a high-risk population that has had myocardial infarction. I'd probably want to do it for at least 2 years.”

Dr. Spiegel said that the current standard of care for older patients with osteoarthritis has “overtaken” the overall impact of the SUCCESS-1 study findings.

“The reality is that people are moving to adding a proton pump inhibitor to an NSAID when [osteoarthritis] patients exceed the age of 65 or if they're put on aspirin,” he said. “They're not moving to COX-2 inhibitor, and this study doesn't give me any more reason to put someone on a COX-2 inhibitor as opposed to just adding a PPI to an NSAID, which is overall a cheaper thing to do. [That approach] is more relevant because it's cheaper, it's cost effective, and there's no risk of MI as there is with COX-2 inhibitors. In fact, there's less overall dyspepsia in patients who are on an NSAID plus a PPI, compared to [those on] a COX-2 inhibitor.”

Dr. Singh disclosed that he received research support from Searle Pharmaceuticals, Pharmacia, Pfizer, Merck & Co., Boehringer Ingelheim, TAP Pharmaceuticals, Wyeth, Altana Pharma, GlaxoSmithKline, Novartis Pharmaceuticals Corp., and Centocor Inc.

The finding 'shows conclusively that celecoxib does reduce the risk of upper GI complications.' DR. SINGH

Celecoxib is just as effective as naproxen and diclofenac for treating osteoarthritis, but it causes significantly fewer serious upper gastrointestinal events, compared with the other agents, according to data from a large international study.

The finding “shows conclusively that celecoxib does reduce the risk of upper GI complications, compared to conventional NSAIDs,” the study's lead author, Dr. Gurkirpal Singh, said. “Up until now managed care has been saying there is no evidence in a randomized, clinical trial that celecoxib is better than NSAIDs in reducing GI bleeding. But here it is; these are level 1 data that conclusively prove that.”

However, Dr. Brennan M.R. Spiegel noted that while the difference favoring celecoxib reached statistical significance in the study, the actual difference was a matter of 1 patient per 100 patient-years, which “is a tiny difference that to me is not enough to warrant spending as much money as we do on COX-2 inhibitors,” said Dr. Spiegel, of the division of digestive diseases at the University of California, Los Angeles.

He added that the study is “notable because it's very large, [but] I believed it before that GI events are less common with coxibs than with NSAIDs. I didn't need another study to demonstrate that.”

In a trial called the Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1), Dr. Gurkirpal and his associates randomly assigned 13,194 osteoarthritis patients from 39 countries to double-blinded treatment with celecoxib 100 mg b.i.d., celecoxib 200 mg b.i.d., or nonselective NSAID therapy for 12 weeks. The NSAID therapy consisted of diclofenac 50 mg b.i.d. or naproxen 500 mg b.i.d. (Am. J. Med. 2006; 119:255–66).

Patients with a history of two or more episodes of active peptic ulceration were excluded from the study, as were those with gastrointestinal bleeding or recurrent gastric or duodenal ulcers and those with an esophageal, gastric, or duodenal ulcer within a month prior to randomization. Patients with active gastrointestinal disease or any condition that required NSAID therapy were also excluded from the study.

The mean age of study participants was 62 years, 76% were women, and 80% were white, reported Dr. Singh, of the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. The mean duration of osteoarthritis was 8 years.

Instruments used to measure efficacy included the Patient's Assessment of Arthritis Pain-Visual Analog Scale, Patients' Global Assessment of Arthritis, and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Serious GI events were evaluated by two independent committees that were blinded to patient randomization.

The researchers reported that the primary efficacy measures for both doses of celecoxib were equally effective as the NSAIDs in treating osteoarthritis.

There were 37 confirmed upper GI events: 19 in the patients who took the NSAIDs and 18 in the patients who took celecoxib. That translated into a rate of 2.1 per 100 patient-years for patients who took the NSAIDs vs. a rate of 1.0 per 100 patient-years for those who took celecoxib. The difference was statistically significant with a P value of .023.

A key limitation of the study, Dr. Singh said, is the fact that it was not powered to detect differences in terms of cardiovascular adverse events. “So we can't make any conclusion about that,” he said. “We did not see any statistically significant differences [between treatment groups], but at the time the study was designed, [concerns about COX-2 inhibitors and risk of] myocardial infarction were not an issue, so that's not something we followed.”

To tease that information out, he added, “you'd need a larger study over a longer period of time, perhaps in a high-risk population that has had myocardial infarction. I'd probably want to do it for at least 2 years.”

Dr. Spiegel said that the current standard of care for older patients with osteoarthritis has “overtaken” the overall impact of the SUCCESS-1 study findings.

“The reality is that people are moving to adding a proton pump inhibitor to an NSAID when [osteoarthritis] patients exceed the age of 65 or if they're put on aspirin,” he said. “They're not moving to COX-2 inhibitor, and this study doesn't give me any more reason to put someone on a COX-2 inhibitor as opposed to just adding a PPI to an NSAID, which is overall a cheaper thing to do. [That approach] is more relevant because it's cheaper, it's cost effective, and there's no risk of MI as there is with COX-2 inhibitors. In fact, there's less overall dyspepsia in patients who are on an NSAID plus a PPI, compared to [those on] a COX-2 inhibitor.”

Dr. Singh disclosed that he received research support from Searle Pharmaceuticals, Pharmacia, Pfizer, Merck & Co., Boehringer Ingelheim, TAP Pharmaceuticals, Wyeth, Altana Pharma, GlaxoSmithKline, Novartis Pharmaceuticals Corp., and Centocor Inc.

The finding 'shows conclusively that celecoxib does reduce the risk of upper GI complications.' DR. SINGH

Type 1 Diabetic Women Have Low BMD

Women with type 1 diabetes should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause, said Elsa S. Strotmeyer, Ph.D., and her associates of the University of Pittsburgh.

Reported fracture rates were higher and bone mineral density (BMD) was lower in 67 premenopausal women aged 35–55 with type 1 diabetes than among 237 nondiabetic women, Dr. Strotmeyer and her associates said (Diabetes Care 2006;29:306–11).

Compared with the nondiabetic women, those with type 1 diabetes were younger (43.1 vs. 45.2 years) and weighed less (69.1 vs. 74.5 kg). One-third of the diabetic women reported having had a fracture after age 20 years, compared with less than a quarter of the nondiabetics.

Type 1 diabetes was associated with a 7.5% lower total hip BMD, 6.1% lower BMD in the femoral neck, 2.9% reduced whole-body BMD, and 15.8% lower calcaneal broadband ultrasound attenuation (BUA). All the differences were significant. Adjusting for age, lean mass, and fat mass reduced but did not eliminate any of the differences, they said.

After adjustment for age, neither duration of diabetes nor hemoglobin A_1c levels were significantly associated with BMD or BUA. Blindness (10.6% of the diabetic women vs. 0.4% of the controls) was associated with lower femoral neck and whole-body BMD, and reduced detection of the 10-g monofilament was related to lower femoral neck BMD after adjusting for age and diabetes duration.

The observed differences in BMD at multiple sites approached one standard deviation, which may confer an approximately doubled risk for hip fracture.

The large decrease in calcaneal BUA in the type 1 diabetic women suggests that peripheral bone sites may be even more compromised than other sites, Dr. Strotmeyer and her associates said.

Infections Prolong Elderly Surgery Stay

Elderly patients who developed surgical site infections after undergoing orthopedic surgery had significantly longer hospital stays, Dr. Jeanne Lee wrote in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Infection was an independent predictor of prolonged stay according to both bivariate and multivariate analyses in the outcomes study, conducted by Dr. Lee and colleagues at Duke University in Durham, N.C.

The study was conducted in eight hospitals between June 1991 and July 2002. The most common procedures were hip arthroplasty in 74 patients (22%), fracture repair in 55 patients (16%), and knee arthroplasty in 40 patients (12%). Staphylococcus aureus was the dominant pathogen, associated with 95 infections (56%), and 55% of these pathogens were methicillin resistant.

The mean length of stay was 13 days among 169 infected patients, compared with 4 days among 171 uninfected controls. The patients' mean age was 75 years, 66% were women, and 83% were Caucasian.

Other predictors of prolonged hospital stay included an inability to bathe independently, undergoing procedures of longer duration, postoperative glucose greater than 200 mg/dL, and having procedures on the same day as hospitalization.

The meeting was sponsored by the American Society for Microbiology.

Many Intercarpal Fusions Fail Early

Many patients who undergo intercarpal fusion later require total wrist arthrodesis, Dr. Samuel Koo and his colleagues reported at the annual meeting of the American Association for Hand Surgery.

The conversion rate was 17% in a retrospective analysis of data available on 72 of 90 consecutive patients who had intercarpal fusion from 1990 and 2002 performed by three surgeons.

The initial diagnosis in 80% of patients was posttraumatic arthrosis. The cohort of 54 men and 18 women had an average age of 35 years. Worker's compensation patients comprised about 75% of the cohort.

Midcarpal fusions were significantly more likely to fail than triscaphe, lunotriquetral, and radiocarpal fusions. Conversion to total wrist arthrodesis occurred in 9 of 32 (28%) midcarpal fusions, 2 of 24 (8%) triscaphe fusions, and 1 of 10 (10%) lunotriquetral fusions. None of the six radiocarpal fusions performed subsequently required total wrist arthrodesis. The average follow-up was 37 months.

More than half the conversions occurred within 11 months, and all but one occurred at less than 2 years. The average time from initial surgery to total wrist fusion was 13 months, said Dr. Koo of Northwestern University in Chicago. Age, gender, and worker's compensation status did not influence conversion rates.

Limitations of the study include its retrospective design, small sample size, and possible bias introduced by excluding patients in the initial study group due to incomplete charts, Dr. Koo said.

Type 1 Diabetic Women Have Low BMD

Women with type 1 diabetes should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause, said Elsa S. Strotmeyer, Ph.D., and her associates of the University of Pittsburgh.

Reported fracture rates were higher and bone mineral density (BMD) was lower in 67 premenopausal women aged 35–55 with type 1 diabetes than among 237 nondiabetic women, Dr. Strotmeyer and her associates said (Diabetes Care 2006;29:306–11).

Compared with the nondiabetic women, those with type 1 diabetes were younger (43.1 vs. 45.2 years) and weighed less (69.1 vs. 74.5 kg). One-third of the diabetic women reported having had a fracture after age 20 years, compared with less than a quarter of the nondiabetics.

Type 1 diabetes was associated with a 7.5% lower total hip BMD, 6.1% lower BMD in the femoral neck, 2.9% reduced whole-body BMD, and 15.8% lower calcaneal broadband ultrasound attenuation (BUA). All the differences were significant. Adjusting for age, lean mass, and fat mass reduced but did not eliminate any of the differences, they said.

After adjustment for age, neither duration of diabetes nor hemoglobin A_1c levels were significantly associated with BMD or BUA. Blindness (10.6% of the diabetic women vs. 0.4% of the controls) was associated with lower femoral neck and whole-body BMD, and reduced detection of the 10-g monofilament was related to lower femoral neck BMD after adjusting for age and diabetes duration.

The observed differences in BMD at multiple sites approached one standard deviation, which may confer an approximately doubled risk for hip fracture.

The large decrease in calcaneal BUA in the type 1 diabetic women suggests that peripheral bone sites may be even more compromised than other sites, Dr. Strotmeyer and her associates said.

Infections Prolong Elderly Surgery Stay

Elderly patients who developed surgical site infections after undergoing orthopedic surgery had significantly longer hospital stays, Dr. Jeanne Lee wrote in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Infection was an independent predictor of prolonged stay according to both bivariate and multivariate analyses in the outcomes study, conducted by Dr. Lee and colleagues at Duke University in Durham, N.C.

The study was conducted in eight hospitals between June 1991 and July 2002. The most common procedures were hip arthroplasty in 74 patients (22%), fracture repair in 55 patients (16%), and knee arthroplasty in 40 patients (12%). Staphylococcus aureus was the dominant pathogen, associated with 95 infections (56%), and 55% of these pathogens were methicillin resistant.

The mean length of stay was 13 days among 169 infected patients, compared with 4 days among 171 uninfected controls. The patients' mean age was 75 years, 66% were women, and 83% were Caucasian.

Other predictors of prolonged hospital stay included an inability to bathe independently, undergoing procedures of longer duration, postoperative glucose greater than 200 mg/dL, and having procedures on the same day as hospitalization.

The meeting was sponsored by the American Society for Microbiology.

Many Intercarpal Fusions Fail Early

Many patients who undergo intercarpal fusion later require total wrist arthrodesis, Dr. Samuel Koo and his colleagues reported at the annual meeting of the American Association for Hand Surgery.

The conversion rate was 17% in a retrospective analysis of data available on 72 of 90 consecutive patients who had intercarpal fusion from 1990 and 2002 performed by three surgeons.

The initial diagnosis in 80% of patients was posttraumatic arthrosis. The cohort of 54 men and 18 women had an average age of 35 years. Worker's compensation patients comprised about 75% of the cohort.

Midcarpal fusions were significantly more likely to fail than triscaphe, lunotriquetral, and radiocarpal fusions. Conversion to total wrist arthrodesis occurred in 9 of 32 (28%) midcarpal fusions, 2 of 24 (8%) triscaphe fusions, and 1 of 10 (10%) lunotriquetral fusions. None of the six radiocarpal fusions performed subsequently required total wrist arthrodesis. The average follow-up was 37 months.

More than half the conversions occurred within 11 months, and all but one occurred at less than 2 years. The average time from initial surgery to total wrist fusion was 13 months, said Dr. Koo of Northwestern University in Chicago. Age, gender, and worker's compensation status did not influence conversion rates.

Limitations of the study include its retrospective design, small sample size, and possible bias introduced by excluding patients in the initial study group due to incomplete charts, Dr. Koo said.

Type 1 Diabetic Women Have Low BMD

Women with type 1 diabetes should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause, said Elsa S. Strotmeyer, Ph.D., and her associates of the University of Pittsburgh.

Reported fracture rates were higher and bone mineral density (BMD) was lower in 67 premenopausal women aged 35–55 with type 1 diabetes than among 237 nondiabetic women, Dr. Strotmeyer and her associates said (Diabetes Care 2006;29:306–11).

Compared with the nondiabetic women, those with type 1 diabetes were younger (43.1 vs. 45.2 years) and weighed less (69.1 vs. 74.5 kg). One-third of the diabetic women reported having had a fracture after age 20 years, compared with less than a quarter of the nondiabetics.

Type 1 diabetes was associated with a 7.5% lower total hip BMD, 6.1% lower BMD in the femoral neck, 2.9% reduced whole-body BMD, and 15.8% lower calcaneal broadband ultrasound attenuation (BUA). All the differences were significant. Adjusting for age, lean mass, and fat mass reduced but did not eliminate any of the differences, they said.

After adjustment for age, neither duration of diabetes nor hemoglobin A_1c levels were significantly associated with BMD or BUA. Blindness (10.6% of the diabetic women vs. 0.4% of the controls) was associated with lower femoral neck and whole-body BMD, and reduced detection of the 10-g monofilament was related to lower femoral neck BMD after adjusting for age and diabetes duration.

The observed differences in BMD at multiple sites approached one standard deviation, which may confer an approximately doubled risk for hip fracture.

The large decrease in calcaneal BUA in the type 1 diabetic women suggests that peripheral bone sites may be even more compromised than other sites, Dr. Strotmeyer and her associates said.

Infections Prolong Elderly Surgery Stay

Elderly patients who developed surgical site infections after undergoing orthopedic surgery had significantly longer hospital stays, Dr. Jeanne Lee wrote in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Infection was an independent predictor of prolonged stay according to both bivariate and multivariate analyses in the outcomes study, conducted by Dr. Lee and colleagues at Duke University in Durham, N.C.

The study was conducted in eight hospitals between June 1991 and July 2002. The most common procedures were hip arthroplasty in 74 patients (22%), fracture repair in 55 patients (16%), and knee arthroplasty in 40 patients (12%). Staphylococcus aureus was the dominant pathogen, associated with 95 infections (56%), and 55% of these pathogens were methicillin resistant.

The mean length of stay was 13 days among 169 infected patients, compared with 4 days among 171 uninfected controls. The patients' mean age was 75 years, 66% were women, and 83% were Caucasian.

Other predictors of prolonged hospital stay included an inability to bathe independently, undergoing procedures of longer duration, postoperative glucose greater than 200 mg/dL, and having procedures on the same day as hospitalization.

The meeting was sponsored by the American Society for Microbiology.

Many Intercarpal Fusions Fail Early

Many patients who undergo intercarpal fusion later require total wrist arthrodesis, Dr. Samuel Koo and his colleagues reported at the annual meeting of the American Association for Hand Surgery.

The conversion rate was 17% in a retrospective analysis of data available on 72 of 90 consecutive patients who had intercarpal fusion from 1990 and 2002 performed by three surgeons.

The initial diagnosis in 80% of patients was posttraumatic arthrosis. The cohort of 54 men and 18 women had an average age of 35 years. Worker's compensation patients comprised about 75% of the cohort.

Midcarpal fusions were significantly more likely to fail than triscaphe, lunotriquetral, and radiocarpal fusions. Conversion to total wrist arthrodesis occurred in 9 of 32 (28%) midcarpal fusions, 2 of 24 (8%) triscaphe fusions, and 1 of 10 (10%) lunotriquetral fusions. None of the six radiocarpal fusions performed subsequently required total wrist arthrodesis. The average follow-up was 37 months.

More than half the conversions occurred within 11 months, and all but one occurred at less than 2 years. The average time from initial surgery to total wrist fusion was 13 months, said Dr. Koo of Northwestern University in Chicago. Age, gender, and worker's compensation status did not influence conversion rates.

Limitations of the study include its retrospective design, small sample size, and possible bias introduced by excluding patients in the initial study group due to incomplete charts, Dr. Koo said.

The U.S. Surgeon General and the U.S. Department of Health and Human Services have launched an initiative to encourage families to learn more about their family health history. The initiative features a Web-enabled tool to help users organize family medical information and present this information to family physicians. The tool can be accessed at https://familyhistory.hhs.gov

The U.S. Surgeon General and the U.S. Department of Health and Human Services have launched an initiative to encourage families to learn more about their family health history. The initiative features a Web-enabled tool to help users organize family medical information and present this information to family physicians. The tool can be accessed at https://familyhistory.hhs.gov

The U.S. Surgeon General and the U.S. Department of Health and Human Services have launched an initiative to encourage families to learn more about their family health history. The initiative features a Web-enabled tool to help users organize family medical information and present this information to family physicians. The tool can be accessed at https://familyhistory.hhs.gov

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

SNOWMASS, COLO. — Extraarticular disease occurs in almost half of all rheumatoid arthritis patients, and greatly increases the risk of premature mortality, Dr. Eric L. Matteson reported at a symposium sponsored by the American College of Rheumatology.

In a review of 609 incident cases of rheumatoid arthritis occurring in Rochester between 1955 and 1995 and followed through 2000, Dr. Matteson of the Mayo Clinic, Rochester, Minn., and his colleagues found that 46% of patients with rheumatoid arthritis developed some extraarticular disease.

The most common extraarticular manifestations in patients included subcutaneous nodules (34%), Sjögren's syndrome (11%), pulmonary fibrosis (7%), pericarditis (5%), and pleuritis (5%). The least common—occurring in 1% or fewer of patients—included neuropathy, xerostomia, and amyloidosis.

Their review also found that the likelihood of premature mortality was greatly increased by extraarticular disease; for example, a female rheumatoid arthritis patient aged 50 years with vasculitis, pericarditis, pleuritis, or pulmonary fibrosis had a life expectancy that was 13–15 years shorter than that of a healthy peer. Male patients with the same manifestations were found to have a life expectancy 15 years shorter than that of healthy peers.

When Dr. Matteson and his colleagues plotted the survival curve of the patients against that of the general Rochester population, there was a significant difference in survival. But when they took out the patients with extraarticular disease and compared only patients with rheumatoid arthritis without extraarticular disease, there was no difference. “The impact is profound,” he said.

Analysis of data showed that the relevant factors most associated with extraarticular disease in patients were antinuclear antibody positivity, male gender, and smoking.

Extraarticular disease was reported by 60% of the rheumatoid arthritis patients who reported having ever smoked. The association has been noted before in other investigations, and some of that evidence suggests that smoking actually drives the disease process, he said.

Rates of extraarticular disease may be different now in the era of biologic treatment, Dr. Matteson allowed. However, during the time of this review, there was no improvement in the incidence rate of extraarticular disease.

Infliximab therapy for rheumatoid arthritis improves patients' levels of high-density lipoprotein but does not make them any less vulnerable to cardiovascular disease because it also raises their levels of low-density lipoprotein, according to a new study.

Infliximab therapy had the effect of increasing serum levels of total cholesterol and both HDL and LDL cholesterol, correlating with a decrease of joint inflammation.

But infliximab does not reduce the risk of cardiovascular disease, the most common cause of premature death in rheumatoid arthritis patients.

Researchers at Cochin Hospital in Paris analyzed the cholesterol levels of 56 consecutive rheumatoid arthritis patients undergoing infliximab therapy. The researchers compared their cholesterol levels with those of a group of 56 rheumatoid arthritis patients not receiving infused infliximab and a control population of 56 without rheumatoid arthritis.

The researchers found that because the infliximab therapy did not change the ratio of HDL to LDL or total cholesterol, the cardiovascular risk did not change for the infliximab therapy patients (Clin. Chim. Acta. 2006;365:143–8).

At baseline, both of the rheumatoid arthritis groups had significantly higher atherogenic profiles than the control group, both in their ratio of LDL to HDL and HDL to total cholesterol. They also had significantly higher HDL levels.

After treatment at baseline, 2 weeks, 6 weeks, and every 8 weeks thereafter, total cholesterol levels in the study group increased from 5 mmol/L at baseline to 5.9 mmol/L at 6 weeks and 6 mmol/L at 30 weeks.

The mean ratio of LDL to HDL did not change significantly, however—2.6 at baseline, 2.7 at 6 weeks, and 2.5 at 30 weeks.

The mean ratio of total cholesterol to HDL did not change, either: 4.3 at baseline, 4.8 at 6 weeks, and 4.4 at 30 weeks.

The results are a departure from those from classic disease-modifying antirheumatic drugs, which have been shown to lower patients' atherogenic profiles, coauthor Dr. Didier Borderie said in an interview.

The study results show that “physicians have to be attentive to the lipid profile of their patients and to evaluate the atherogenic ratio of their patients before and regularly during infliximab therapy,” according to Dr. Borderie, of Cochin Hospital.

Infliximab therapy for rheumatoid arthritis improves patients' levels of high-density lipoprotein but does not make them any less vulnerable to cardiovascular disease because it also raises their levels of low-density lipoprotein, according to a new study.

Infliximab therapy had the effect of increasing serum levels of total cholesterol and both HDL and LDL cholesterol, correlating with a decrease of joint inflammation.

But infliximab does not reduce the risk of cardiovascular disease, the most common cause of premature death in rheumatoid arthritis patients.

Researchers at Cochin Hospital in Paris analyzed the cholesterol levels of 56 consecutive rheumatoid arthritis patients undergoing infliximab therapy. The researchers compared their cholesterol levels with those of a group of 56 rheumatoid arthritis patients not receiving infused infliximab and a control population of 56 without rheumatoid arthritis.

The researchers found that because the infliximab therapy did not change the ratio of HDL to LDL or total cholesterol, the cardiovascular risk did not change for the infliximab therapy patients (Clin. Chim. Acta. 2006;365:143–8).

At baseline, both of the rheumatoid arthritis groups had significantly higher atherogenic profiles than the control group, both in their ratio of LDL to HDL and HDL to total cholesterol. They also had significantly higher HDL levels.

After treatment at baseline, 2 weeks, 6 weeks, and every 8 weeks thereafter, total cholesterol levels in the study group increased from 5 mmol/L at baseline to 5.9 mmol/L at 6 weeks and 6 mmol/L at 30 weeks.

The mean ratio of LDL to HDL did not change significantly, however—2.6 at baseline, 2.7 at 6 weeks, and 2.5 at 30 weeks.

The mean ratio of total cholesterol to HDL did not change, either: 4.3 at baseline, 4.8 at 6 weeks, and 4.4 at 30 weeks.

The results are a departure from those from classic disease-modifying antirheumatic drugs, which have been shown to lower patients' atherogenic profiles, coauthor Dr. Didier Borderie said in an interview.

The study results show that “physicians have to be attentive to the lipid profile of their patients and to evaluate the atherogenic ratio of their patients before and regularly during infliximab therapy,” according to Dr. Borderie, of Cochin Hospital.

Infliximab therapy for rheumatoid arthritis improves patients' levels of high-density lipoprotein but does not make them any less vulnerable to cardiovascular disease because it also raises their levels of low-density lipoprotein, according to a new study.

Infliximab therapy had the effect of increasing serum levels of total cholesterol and both HDL and LDL cholesterol, correlating with a decrease of joint inflammation.

But infliximab does not reduce the risk of cardiovascular disease, the most common cause of premature death in rheumatoid arthritis patients.

Researchers at Cochin Hospital in Paris analyzed the cholesterol levels of 56 consecutive rheumatoid arthritis patients undergoing infliximab therapy. The researchers compared their cholesterol levels with those of a group of 56 rheumatoid arthritis patients not receiving infused infliximab and a control population of 56 without rheumatoid arthritis.

The researchers found that because the infliximab therapy did not change the ratio of HDL to LDL or total cholesterol, the cardiovascular risk did not change for the infliximab therapy patients (Clin. Chim. Acta. 2006;365:143–8).

At baseline, both of the rheumatoid arthritis groups had significantly higher atherogenic profiles than the control group, both in their ratio of LDL to HDL and HDL to total cholesterol. They also had significantly higher HDL levels.

After treatment at baseline, 2 weeks, 6 weeks, and every 8 weeks thereafter, total cholesterol levels in the study group increased from 5 mmol/L at baseline to 5.9 mmol/L at 6 weeks and 6 mmol/L at 30 weeks.

The mean ratio of LDL to HDL did not change significantly, however—2.6 at baseline, 2.7 at 6 weeks, and 2.5 at 30 weeks.

The mean ratio of total cholesterol to HDL did not change, either: 4.3 at baseline, 4.8 at 6 weeks, and 4.4 at 30 weeks.

The results are a departure from those from classic disease-modifying antirheumatic drugs, which have been shown to lower patients' atherogenic profiles, coauthor Dr. Didier Borderie said in an interview.

The study results show that “physicians have to be attentive to the lipid profile of their patients and to evaluate the atherogenic ratio of their patients before and regularly during infliximab therapy,” according to Dr. Borderie, of Cochin Hospital.