Heidi Splete

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years.

However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis.

Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. “Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR,” the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland. The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted.

View on the News

Focus on Early Intervention

It is important to study the relationships between osteoarthritis and cardiovascular health because both are chronic low-grade inflammatory diseases. The lack of association between severe osteoarthritis and atherosclerosis in the majority of patients in this study is not surprising. We see the same thing with osteoporosis, another disease of aging in which there is low-grade inflammation, which causes a disease over time.

Genetics and diet are some factors that might affect the association between hand OA and atherosclerosis in women, which might have been factors in this study.

There are various challenges to studying the relationship between osteoarthritis and atherosclerosis.

For example, it takes time to see the clinical disease and, because of that, we need to use animal models and try to understand both the disease mechanism and how we might intervene.

When planning future studies, researchers in this area need to talk to each other and design studies to intervene before diseases become clinically apparent.

DR. NANCY LANE is a professor at the University of California, Davis, and director of the UC Davis Center for Healthy Aging. Her specialties include internal medicine, rheumatology, and allergy and clinical immunology. She said she had no relevant financial disclosures.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years.

However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis.

Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. “Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR,” the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland. The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted.

View on the News

Focus on Early Intervention

It is important to study the relationships between osteoarthritis and cardiovascular health because both are chronic low-grade inflammatory diseases. The lack of association between severe osteoarthritis and atherosclerosis in the majority of patients in this study is not surprising. We see the same thing with osteoporosis, another disease of aging in which there is low-grade inflammation, which causes a disease over time.

Genetics and diet are some factors that might affect the association between hand OA and atherosclerosis in women, which might have been factors in this study.

There are various challenges to studying the relationship between osteoarthritis and atherosclerosis.

For example, it takes time to see the clinical disease and, because of that, we need to use animal models and try to understand both the disease mechanism and how we might intervene.

When planning future studies, researchers in this area need to talk to each other and design studies to intervene before diseases become clinically apparent.

DR. NANCY LANE is a professor at the University of California, Davis, and director of the UC Davis Center for Healthy Aging. Her specialties include internal medicine, rheumatology, and allergy and clinical immunology. She said she had no relevant financial disclosures.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years.

However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis.

Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. “Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR,” the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland. The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted.

View on the News

Focus on Early Intervention

It is important to study the relationships between osteoarthritis and cardiovascular health because both are chronic low-grade inflammatory diseases. The lack of association between severe osteoarthritis and atherosclerosis in the majority of patients in this study is not surprising. We see the same thing with osteoporosis, another disease of aging in which there is low-grade inflammation, which causes a disease over time.

Genetics and diet are some factors that might affect the association between hand OA and atherosclerosis in women, which might have been factors in this study.

There are various challenges to studying the relationship between osteoarthritis and atherosclerosis.

For example, it takes time to see the clinical disease and, because of that, we need to use animal models and try to understand both the disease mechanism and how we might intervene.

When planning future studies, researchers in this area need to talk to each other and design studies to intervene before diseases become clinically apparent.

DR. NANCY LANE is a professor at the University of California, Davis, and director of the UC Davis Center for Healthy Aging. Her specialties include internal medicine, rheumatology, and allergy and clinical immunology. She said she had no relevant financial disclosures.

The transition of adolescents with congenital heart disease from pediatric to adult care should be targeted to the teen's emotional and physical developmental status, according to a scientific statement from the American Heart Association.

More children with congenital heart disease are surviving to adulthood, creating a need for programs to help them transition from pediatric to adult medical environments, said writing committee cochairs Dr. Craig Sable of Children's National Medical Center in Washington and Dr. Elyse Foster of the University of California, San Francisco, and their colleagues wrote in “Best Practices in Managing Transition to Adulthood for Adolescents with Congenital Heart Disease: The Transition Process and Medical and Psychosocial Issues.”

An ideal transition program should “foster personal and medical independence and a greater sense of control over health, [health care] decisions, and psychosocial environment,” the committee wrote (Circulation 2011 Feb. 28 [doi:10.1061/CIR.0b013e3182107c56]).

The statement recommends actively involving adolescents in the transition process, but timing the transition according to the patient's emotional and developmental maturity. The pediatric cardiologist should initiate a transition plan, and work with the adolescent to develop the plan. Clinicians should begin to direct health discussions toward the teen rather than the parent, and should encourage teens to talk privately about their quality of life concerns, such as physical restrictions, school and peer issues, and other social relationships.

Clinicians should also recognize parents' fears and concerns, and solicit their opinions about what quality of life issues their teen might have.

Ideally, an adolescent with CHD will have a medical home with a primary care provider who will maintain a confidential record of the patient's medical information, the committee wrote. Once the patient is established with a cardiologist, that clinician should update the patient's records with the primary care provider.

Surgical considerations for adolescents with CHD should include consulting an adult CHD (ACHD) expert during preoperative planning for elective surgery, choosing a clinical setting (pediatric or adult) based on the patient's preferences and developmental status, and enlisting an anesthesiologist familiar with the physiology of adolescent CHD.

Additional issues to raise with adolescent CHD patients include genetic testing, sexuality and contraception, exercise, employment, and insurance. In all cases, discussion should be individualized based on the teen's developmental status.

Many pediatric cardiologists continue to care for adolescents with CHD and developmental disabilities well into adulthood, but the AHA statement endorses the creation of individual transition plans to move these patients into successful adult CHD care.

The statement reviewed the following three key elements of the transition process from pediatric to adult CHD care that apply regardless of the specific transition model:

▸ Pretransition. Introduce children with CHD to the idea of managing their own health during childhood, so they can develop the necessary skills. One model for pretransition involves a nurse practitioner or physician assistant, who starts by counseling the adolescent about diet and exercise, contraception and pregnancy, high-risk behaviors, and other concerns.

▸ Transition. Use a transition curriculum to educate teens about their medical history, diagnosis, and how their hearts are different. Teens in transition to adult care CHD should learn which symptoms are cause for concern, and understand different treatment options. Also, transitioning teens need to learn how to handle health insurance and how to schedule routine care visits and follow-up visits with specialists.

▸ Transfer. Transfer care when adolescent CHD patients have shown an ability to meet their own health care needs independent of their families. The AHA recommends avoiding transfer from pediatric to adult care during medical crises or complications such as pregnancy, mental illness, or noncompliance, to avoid additional psychological stress for the patient.

The recommendations were presented on behalf of the American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease.

Dr. Sable had no financial conflicts to disclose. Dr. Foster has received research funding from Boston Scientific, Guidant, and Evalve Inc.

Adolescents should be actively involved in the transition process to adult care.

Source DR. FOSTER

View on the News

Make Move Before Hormones Kick In

So many life changes take place during the late teens and early twenties, including evolving psychosocial, economic, geographic, and education or work factors. Preparing young people with chronic disease to transition to adult care must include an understanding of this framework in order to effectively transfer them to a system that requires self-determination. Currently, this is done in a hit-or-miss fashion. Production of guidelines, developed by a consensus process, is an essential step toward changing practice patterns and planning for the institutional resources needed to facilitate successful transfer.

Surveys of pediatricians indicate that finding time to provide adolescents with appropriate guidance for their health care issues is a significant concern. Within pediatric cardiology programs, the guidance around lifestyle and health care is often provided by allied health professionals, but these resources are stretched thin.

One of the most serious challenges facing doctors and patients is the lack of funding for case management that spans the period of transfer. Many of the problems faced by young people – particularly those with chronic disease – relate to financial and psychosocial issues. Although most states provide funding to support advanced practice nursing and social services to pediatric programs, this support does not exist in the adult health care system except in the most extreme cases. Successful transfer requires not only a smooth takeoff, but also a secure landing. These resources must be developed for at least the 20-something population to ensure continued access to the appropriate health care providers.

My advice to clinicians is to start before the hormone surge. Preteens are often the most receptive. It's helpful to begin the conversation with the patient and family as soon as possible, and to repeat it often.

ROBERTA G. WILLIAMS, M.D., is a pediatric cardiologist at Children's Hospital in Los Angeles. She is a member of the committee that developed the statement. She reported that she had no financial disclosures.

The transition of adolescents with congenital heart disease from pediatric to adult care should be targeted to the teen's emotional and physical developmental status, according to a scientific statement from the American Heart Association.

More children with congenital heart disease are surviving to adulthood, creating a need for programs to help them transition from pediatric to adult medical environments, said writing committee cochairs Dr. Craig Sable of Children's National Medical Center in Washington and Dr. Elyse Foster of the University of California, San Francisco, and their colleagues wrote in “Best Practices in Managing Transition to Adulthood for Adolescents with Congenital Heart Disease: The Transition Process and Medical and Psychosocial Issues.”

An ideal transition program should “foster personal and medical independence and a greater sense of control over health, [health care] decisions, and psychosocial environment,” the committee wrote (Circulation 2011 Feb. 28 [doi:10.1061/CIR.0b013e3182107c56]).

The statement recommends actively involving adolescents in the transition process, but timing the transition according to the patient's emotional and developmental maturity. The pediatric cardiologist should initiate a transition plan, and work with the adolescent to develop the plan. Clinicians should begin to direct health discussions toward the teen rather than the parent, and should encourage teens to talk privately about their quality of life concerns, such as physical restrictions, school and peer issues, and other social relationships.

Clinicians should also recognize parents' fears and concerns, and solicit their opinions about what quality of life issues their teen might have.

Ideally, an adolescent with CHD will have a medical home with a primary care provider who will maintain a confidential record of the patient's medical information, the committee wrote. Once the patient is established with a cardiologist, that clinician should update the patient's records with the primary care provider.

Surgical considerations for adolescents with CHD should include consulting an adult CHD (ACHD) expert during preoperative planning for elective surgery, choosing a clinical setting (pediatric or adult) based on the patient's preferences and developmental status, and enlisting an anesthesiologist familiar with the physiology of adolescent CHD.

Additional issues to raise with adolescent CHD patients include genetic testing, sexuality and contraception, exercise, employment, and insurance. In all cases, discussion should be individualized based on the teen's developmental status.

Many pediatric cardiologists continue to care for adolescents with CHD and developmental disabilities well into adulthood, but the AHA statement endorses the creation of individual transition plans to move these patients into successful adult CHD care.

The statement reviewed the following three key elements of the transition process from pediatric to adult CHD care that apply regardless of the specific transition model:

▸ Pretransition. Introduce children with CHD to the idea of managing their own health during childhood, so they can develop the necessary skills. One model for pretransition involves a nurse practitioner or physician assistant, who starts by counseling the adolescent about diet and exercise, contraception and pregnancy, high-risk behaviors, and other concerns.

▸ Transition. Use a transition curriculum to educate teens about their medical history, diagnosis, and how their hearts are different. Teens in transition to adult care CHD should learn which symptoms are cause for concern, and understand different treatment options. Also, transitioning teens need to learn how to handle health insurance and how to schedule routine care visits and follow-up visits with specialists.

▸ Transfer. Transfer care when adolescent CHD patients have shown an ability to meet their own health care needs independent of their families. The AHA recommends avoiding transfer from pediatric to adult care during medical crises or complications such as pregnancy, mental illness, or noncompliance, to avoid additional psychological stress for the patient.

The recommendations were presented on behalf of the American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease.

Dr. Sable had no financial conflicts to disclose. Dr. Foster has received research funding from Boston Scientific, Guidant, and Evalve Inc.

Adolescents should be actively involved in the transition process to adult care.

Source DR. FOSTER

View on the News

Make Move Before Hormones Kick In

So many life changes take place during the late teens and early twenties, including evolving psychosocial, economic, geographic, and education or work factors. Preparing young people with chronic disease to transition to adult care must include an understanding of this framework in order to effectively transfer them to a system that requires self-determination. Currently, this is done in a hit-or-miss fashion. Production of guidelines, developed by a consensus process, is an essential step toward changing practice patterns and planning for the institutional resources needed to facilitate successful transfer.

Surveys of pediatricians indicate that finding time to provide adolescents with appropriate guidance for their health care issues is a significant concern. Within pediatric cardiology programs, the guidance around lifestyle and health care is often provided by allied health professionals, but these resources are stretched thin.

One of the most serious challenges facing doctors and patients is the lack of funding for case management that spans the period of transfer. Many of the problems faced by young people – particularly those with chronic disease – relate to financial and psychosocial issues. Although most states provide funding to support advanced practice nursing and social services to pediatric programs, this support does not exist in the adult health care system except in the most extreme cases. Successful transfer requires not only a smooth takeoff, but also a secure landing. These resources must be developed for at least the 20-something population to ensure continued access to the appropriate health care providers.

My advice to clinicians is to start before the hormone surge. Preteens are often the most receptive. It's helpful to begin the conversation with the patient and family as soon as possible, and to repeat it often.

ROBERTA G. WILLIAMS, M.D., is a pediatric cardiologist at Children's Hospital in Los Angeles. She is a member of the committee that developed the statement. She reported that she had no financial disclosures.

The transition of adolescents with congenital heart disease from pediatric to adult care should be targeted to the teen's emotional and physical developmental status, according to a scientific statement from the American Heart Association.

More children with congenital heart disease are surviving to adulthood, creating a need for programs to help them transition from pediatric to adult medical environments, said writing committee cochairs Dr. Craig Sable of Children's National Medical Center in Washington and Dr. Elyse Foster of the University of California, San Francisco, and their colleagues wrote in “Best Practices in Managing Transition to Adulthood for Adolescents with Congenital Heart Disease: The Transition Process and Medical and Psychosocial Issues.”

An ideal transition program should “foster personal and medical independence and a greater sense of control over health, [health care] decisions, and psychosocial environment,” the committee wrote (Circulation 2011 Feb. 28 [doi:10.1061/CIR.0b013e3182107c56]).

The statement recommends actively involving adolescents in the transition process, but timing the transition according to the patient's emotional and developmental maturity. The pediatric cardiologist should initiate a transition plan, and work with the adolescent to develop the plan. Clinicians should begin to direct health discussions toward the teen rather than the parent, and should encourage teens to talk privately about their quality of life concerns, such as physical restrictions, school and peer issues, and other social relationships.

Clinicians should also recognize parents' fears and concerns, and solicit their opinions about what quality of life issues their teen might have.

Ideally, an adolescent with CHD will have a medical home with a primary care provider who will maintain a confidential record of the patient's medical information, the committee wrote. Once the patient is established with a cardiologist, that clinician should update the patient's records with the primary care provider.

Surgical considerations for adolescents with CHD should include consulting an adult CHD (ACHD) expert during preoperative planning for elective surgery, choosing a clinical setting (pediatric or adult) based on the patient's preferences and developmental status, and enlisting an anesthesiologist familiar with the physiology of adolescent CHD.

Additional issues to raise with adolescent CHD patients include genetic testing, sexuality and contraception, exercise, employment, and insurance. In all cases, discussion should be individualized based on the teen's developmental status.

Many pediatric cardiologists continue to care for adolescents with CHD and developmental disabilities well into adulthood, but the AHA statement endorses the creation of individual transition plans to move these patients into successful adult CHD care.

The statement reviewed the following three key elements of the transition process from pediatric to adult CHD care that apply regardless of the specific transition model:

▸ Pretransition. Introduce children with CHD to the idea of managing their own health during childhood, so they can develop the necessary skills. One model for pretransition involves a nurse practitioner or physician assistant, who starts by counseling the adolescent about diet and exercise, contraception and pregnancy, high-risk behaviors, and other concerns.

▸ Transition. Use a transition curriculum to educate teens about their medical history, diagnosis, and how their hearts are different. Teens in transition to adult care CHD should learn which symptoms are cause for concern, and understand different treatment options. Also, transitioning teens need to learn how to handle health insurance and how to schedule routine care visits and follow-up visits with specialists.

▸ Transfer. Transfer care when adolescent CHD patients have shown an ability to meet their own health care needs independent of their families. The AHA recommends avoiding transfer from pediatric to adult care during medical crises or complications such as pregnancy, mental illness, or noncompliance, to avoid additional psychological stress for the patient.

The recommendations were presented on behalf of the American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease.

Dr. Sable had no financial conflicts to disclose. Dr. Foster has received research funding from Boston Scientific, Guidant, and Evalve Inc.

Adolescents should be actively involved in the transition process to adult care.

Source DR. FOSTER

View on the News

Make Move Before Hormones Kick In

So many life changes take place during the late teens and early twenties, including evolving psychosocial, economic, geographic, and education or work factors. Preparing young people with chronic disease to transition to adult care must include an understanding of this framework in order to effectively transfer them to a system that requires self-determination. Currently, this is done in a hit-or-miss fashion. Production of guidelines, developed by a consensus process, is an essential step toward changing practice patterns and planning for the institutional resources needed to facilitate successful transfer.

Surveys of pediatricians indicate that finding time to provide adolescents with appropriate guidance for their health care issues is a significant concern. Within pediatric cardiology programs, the guidance around lifestyle and health care is often provided by allied health professionals, but these resources are stretched thin.

One of the most serious challenges facing doctors and patients is the lack of funding for case management that spans the period of transfer. Many of the problems faced by young people – particularly those with chronic disease – relate to financial and psychosocial issues. Although most states provide funding to support advanced practice nursing and social services to pediatric programs, this support does not exist in the adult health care system except in the most extreme cases. Successful transfer requires not only a smooth takeoff, but also a secure landing. These resources must be developed for at least the 20-something population to ensure continued access to the appropriate health care providers.

My advice to clinicians is to start before the hormone surge. Preteens are often the most receptive. It's helpful to begin the conversation with the patient and family as soon as possible, and to repeat it often.

ROBERTA G. WILLIAMS, M.D., is a pediatric cardiologist at Children's Hospital in Los Angeles. She is a member of the committee that developed the statement. She reported that she had no financial disclosures.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

The U.S. Food and Drug Administration has advised pharmacists to dispense the anticoagulant medication dabigatran etexilate mesylate (Pradaxa) only in the original manufacturer bottles or blister packages because of concerns about product breakdown, according to a MedWatch statement issued on March 30.

In addition, patients should not place Pradaxa capsules in pill boxes or pill organizers, according to the statement. The product should be kept in the original container and should be used within 60 days of opening it.

The storage and handling requirements for Pradaxa, a direct thrombin inhibitor, are listed on the product label and medication guide, but "FDA is concerned that these requirements are not commonly known and are not being followed by Pradaxa users and by pharmacists," the statement said.

The FDA encourages clinicians and patients to report any adverse events or side effects related to Pradaxa to the FDA MedWatch Safety Information and Adverse Event Reporting Program online or by phone at 1-800-332-1088.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Adults who underwent total joint replacement of the hip or knee were not significantly more likely to have atherosclerosis, based on data from 5,170 adults with an average age of 76 years. However, women who had a total joint replacement and hand osteoarthritis were significantly more likely to have atherosclerosis. The results were published online on March 1 in the Annals of the Rheumatic Diseases.

In this study, Dr. Helgi Jonsson of the University of Iceland in Reykjavik and colleagues used total joint replacement (TJR) as an indicator of severe osteoarthritis (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.144980]). The study population included 2,195 men and 2,975 women; 539 patients had total joint replacement, including 316 with total hip replacements (THR), 223 with total knee replacements (TKR), and 31 with both hip and knee replacements.

Overall, women who had a joint replacement showed a nonsignificant trend toward increased coronary calcifications and carotid plaques, but no such associations were seen in men. "Apart from marginally increased aortic calcium in women with TKR, there were no statistical differences in those with and without TKR and THR," the researchers noted.

But the researchers saw a significant upward trend in coronary calcifications among women with hand osteoarthritis (HOA). The difference between the average value of women without either TJR or HOA and the women with both TJR and HOA was significant – approximately 10% – for three markers of atherosclerosis: coronary calcium, periventricular white matter hyperintensities, and carotid plaque.

The data were taken from a subset of older patients in the AGES–Reykjavik Study, a population-based study conducted in Iceland.

The results support findings from previous studies suggesting a link between osteoarthritis and atherosclerosis in women, the researchers noted. "We are currently analyzing a number of ‘midlife’ biomarkers and inflammatory markers available from previous visits in the 40-year-long Reykjavik Study in an attempt to clarify this relationship," they said.

The Reykjavik study was funded by the National Institutes of Health, the National Institute on Aging Intramural Research Program, the Icelandic Heart Association, the Icelandic Parliament, the Icelandic Osteoarthritis Fund, and the University of Iceland Research Fund. The researchers had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Decompressive craniectomy significantly relieved intracranial pressure and shortened hospital stays, but the patients were more likely to have poor functional outcomes 6 months later, based on data from a randomized trial of 155 patients. The results were published online March 25 in the New England Journal of Medicine.

Relief of intracranial pressure is an important part of treating severe traumatic brain injury, but few studies have examined the effectiveness of surgical decompressive craniectomy, a technique that is becoming more common for patients who don’t respond to first-tier therapies, said Dr. D. James Cooper of Monash University in Melbourne, Australia, and colleagues.

In this study, 73 patients underwent early decompressive craniectomy and 82 received standard care (N. Engl. J. Med. 2011 Mar. 25 [doi: 10.1056/NEJMoa1102077]). Baseline injury and demographic characteristics were not significantly different between the two groups, with the exception of significantly fewer patients with reactive pupils in the craniectomy group. The initial primary outcome was the proportion of patients who died, entered a vegetative state, or became severely disabled. After an interim analysis, the primary outcome was revised to the patients’ functional outcome, based on the Extended Glasgow Outcome Scale.

Compared with the standard care group, the mean intracranial pressure after randomization was significantly lower in the craniectomy group (19 mmHg vs. 14 mmHg, respectively) and the number of hours when intracranial pressure was greater than 20 mmHg was significantly lower in the craniectomy group (30 hours vs. 9 hours, respectively). Measures on the intracranial hypoperfusion index and cerebral hypoperfusion index also were significantly lower in the craniectomy group.

In addition, patients in the craniectomy group needed significantly fewer interventions, including venting the cerebrospinal fluid through the ventricular drain and using mannitol, hypertonic saline, neuromuscular blocking drugs, and barbiturates.

However, the primary outcome of functional assessment 6 months after the injury was significantly worse in the craniectomy patients, the researchers noted. Based on the Extended Glasgow Outcome Scale, unfavorable outcomes occurred in 51 craniectomy patients (70%) vs. 42 standard care patients (51%). The results were similar after controlling for predetermined variables, but differences for the risk of an unfavorable outcome were no longer significant after controlling for the baseline difference in pupil reactivity in a post hoc analysis, the researchers noted.

"We had speculated that decompressive craniectomy would decrease intracranial pressure, improve functional outcomes, and decrease the proportion of survivors with severe disability," the researchers wrote. "Decompressive craniectomy instead shifted survivors from a favorable outcome to an unfavorable outcome," they said.

Possible reasons for the poor outcomes in the craniectomy group include expansion of the swollen brain outside the skull during the procedure, and characteristics of the procedure itself, the researchers said. In this study, a standardized surgical approach was used. The approach, modeled on the Polin technique, "included a large bifrontotemporoparietal craniectomy with bilateral dural opening." The researchers noted that some surgeons prefer a unilateral over a bilateral approach, which some nonrandomized studies suggest may have more complications. However, complications are possible with each approach, they said.

Overall, 37% of craniectomy patients and 17% of standard care patients had a least one medical or surgical complication. The most common adverse event was wound infection or breakdown, which occurred in 7% of the craniectomy patients and 9% of the standard care patients.

The researchers recruited adults with severe nonpenetrating brain injury from 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia between December 2002 and April 2010. The patients in this group, known as the Depressive Craniectomy (DECRA) study, were aged 15-59 years.

The results were limited by the lack of blinding for those evaluating the results and by the difference in pupil reactivity between the groups. But the results suggest the need for more research, and "the critical importance of conducting such trials to test common therapies, particularly in patients with complex critical illnesses," the researchers wrote.

The study was funded by several health organizations, including the National Health and Medical Research Council of Australia and the New Zealand Intensive Care Society. Dr. Cooper had no financial conflicts to disclose.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.

Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.

Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.

In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).

During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.

Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.

When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.

The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.

Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.

In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.

The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).

"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).

Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.