Heidi Splete

Major Finding: UPDRS motor scores improved a mean of 8.1 points in patients who received AAV2-GAD, which was significantly more than the 4.7-point improvement seen in patients who underwent a sham procedure.

Data Source: Phase II trial of 45 Parkinson's disease patients with UPDRS motor scores of 25 or greater.

Disclosures: Neurologix funded the trial. Many of the investigators reported serving as speakers or consultants to or receiving grant funding from many companies that manufacture treatments for Parkinson's disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson's disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was “the first successful randomized, double-blind gene therapy trial for a neurological disorder” and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported.

However, glutamic acid decarboxylase (GAD) gene therapy is not the only type of gene therapy under investigation for Parkinson's disease. A separate phase II trial with the gene for the neurotrophic factor neurturin is now enrolling patients.

In the study conducted by Dr. LeWitt and his associates, 22 Parkinson's patients with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the GAD gene into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson's disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson's disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the “off” state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

“The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points” at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator's clinical global impression of Parkinson's disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients' ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study's small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, “it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product,” the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, he said (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

A separate investigational gene therapy treatment for Parkinson's disease, called CERE-120, proved to be safe but lacked efficacy in a recent randomized, sham-controlled, phase II trial that was sponsored by Ceregene Inc. (Lancet Neurol. 2010;9:1164-72). The investigators of that trial blamed its results on the failed delivery of the therapy (consisting of the AAV2 viral vector and the gene for neurturin, a member of the same protein family as glial-derived neurotrophic factor) to dopaminergic neurons.

In the trial, AAV2-neurturin was injected into an area of the brain called the putamen in patients with Parkinson's disease, where the nerve terminals of degenerating dopaminergic neurons reside. However, the investigators realized that neurturin was not being transported effectively to the cell bodies of the dopaminergic neurons, which reside in the substantia nigra (Mov. Disord. 2011;26:27-36).

A new treatment protocol that delivers a larger dose of AAV2-neurturin to the putamen, as well as directly to the substantia nigra, is currently being tested in a new randomized, sham-controlled, phase II trial of approximately 52 Parkinson's disease patients at 11 U.S. centers. The new treatment protocol was successfully given to six patients with Parkinson's disease in a phase I trial and has not been associated with any serious adverse events after 7-13 months of follow-up, according to Ceregene.

The new phase II trial of AAV2-neurturin is partially funded by the Michael J. Fox Foundation.

Jeff Evans contributed to this report.

Major Finding: UPDRS motor scores improved a mean of 8.1 points in patients who received AAV2-GAD, which was significantly more than the 4.7-point improvement seen in patients who underwent a sham procedure.

Data Source: Phase II trial of 45 Parkinson's disease patients with UPDRS motor scores of 25 or greater.

Disclosures: Neurologix funded the trial. Many of the investigators reported serving as speakers or consultants to or receiving grant funding from many companies that manufacture treatments for Parkinson's disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson's disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was “the first successful randomized, double-blind gene therapy trial for a neurological disorder” and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported.

However, glutamic acid decarboxylase (GAD) gene therapy is not the only type of gene therapy under investigation for Parkinson's disease. A separate phase II trial with the gene for the neurotrophic factor neurturin is now enrolling patients.

In the study conducted by Dr. LeWitt and his associates, 22 Parkinson's patients with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the GAD gene into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson's disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson's disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the “off” state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

“The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points” at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator's clinical global impression of Parkinson's disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients' ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study's small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, “it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product,” the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, he said (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

A separate investigational gene therapy treatment for Parkinson's disease, called CERE-120, proved to be safe but lacked efficacy in a recent randomized, sham-controlled, phase II trial that was sponsored by Ceregene Inc. (Lancet Neurol. 2010;9:1164-72). The investigators of that trial blamed its results on the failed delivery of the therapy (consisting of the AAV2 viral vector and the gene for neurturin, a member of the same protein family as glial-derived neurotrophic factor) to dopaminergic neurons.

In the trial, AAV2-neurturin was injected into an area of the brain called the putamen in patients with Parkinson's disease, where the nerve terminals of degenerating dopaminergic neurons reside. However, the investigators realized that neurturin was not being transported effectively to the cell bodies of the dopaminergic neurons, which reside in the substantia nigra (Mov. Disord. 2011;26:27-36).

A new treatment protocol that delivers a larger dose of AAV2-neurturin to the putamen, as well as directly to the substantia nigra, is currently being tested in a new randomized, sham-controlled, phase II trial of approximately 52 Parkinson's disease patients at 11 U.S. centers. The new treatment protocol was successfully given to six patients with Parkinson's disease in a phase I trial and has not been associated with any serious adverse events after 7-13 months of follow-up, according to Ceregene.

The new phase II trial of AAV2-neurturin is partially funded by the Michael J. Fox Foundation.

Jeff Evans contributed to this report.

Major Finding: UPDRS motor scores improved a mean of 8.1 points in patients who received AAV2-GAD, which was significantly more than the 4.7-point improvement seen in patients who underwent a sham procedure.

Data Source: Phase II trial of 45 Parkinson's disease patients with UPDRS motor scores of 25 or greater.

Disclosures: Neurologix funded the trial. Many of the investigators reported serving as speakers or consultants to or receiving grant funding from many companies that manufacture treatments for Parkinson's disease. Dr. Hutchinson had no financial conflicts to disclose.

Direct infusion of the gene for glutamic acid decarboxylase into the subthalamic nucleus of patients with Parkinson's disease significantly improved measures of motor function, compared with patients who underwent a sham procedure, according to the results of a phase II trial in 45 patients.

The study was “the first successful randomized, double-blind gene therapy trial for a neurological disorder” and serves as a proof of concept for similar studies, justifying its continued development, Dr. Peter A. LeWitt of Wayne State University, Detroit, and his colleagues reported.

However, glutamic acid decarboxylase (GAD) gene therapy is not the only type of gene therapy under investigation for Parkinson's disease. A separate phase II trial with the gene for the neurotrophic factor neurturin is now enrolling patients.

In the study conducted by Dr. LeWitt and his associates, 22 Parkinson's patients with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores of 25 or more were randomized to gene therapy and 23 were randomized to sham surgery. The gene therapy involved inserting the GAD gene into the subthalamic nucleus using the adeno-associated viral vector, AAV2.

GAD is the rate-limiting enzyme for the neurotransmitter gamma-aminobutyric acid (GABA). The destruction of nigrostriatal dopaminergic neurons in Parkinson's disease alters the dynamics of inhibitory GABA input to the subthalamic nucleus, which worsens parkinsonian symptoms. Improvement of symptoms has been shown previously with infusions of a GABA agonist into the subthalamic nucleus of Parkinson's disease patients during surgery for deep brain stimulation and also in animal models of parkinsonism.

After 6 months, patients in the AAV2-GAD group showed a 23% improvement (an average 8.1-point decrease) in UPDRS scores in the “off” state (while not on medications), compared with a 13% improvement (an average 4.7-point decrease) in the sham group (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70039-4]).

“The change of UPDRS scores from baseline differed significantly between treatment groups across all three postoperative time points” at 1, 3, and 6 months, the researchers noted.

The only severe adverse event reported during the study period was a case of bowel obstruction in the AAV2-GAD group. Mild and moderate adverse events included headaches and nausea.

In addition, the investigator's clinical global impression of Parkinson's disease severity improved significantly from baseline to 6 months in the treatment group vs. the sham group (3.4 vs. 3.9).

The patients' ages ranged from 30 to 75 years. A total of 6 patients in the treatment group and 2 in the sham group did not receive the complete intervention, leaving efficacy groups of 16 and 21, respectively.

The findings were limited by the study's small size and the possibility of inadequate blinding of the procedures because the patients were awake during their surgeries. However, “it is unlikely that the benefits in the AAV2-GAD treatment group were caused by the temporary placement of catheters in the subthalamic nucleus rather than from the infusion of the gene product,” the researchers wrote.

Although the study findings are promising, questions remain as to how long the effects of the gene therapy will last and what advantages it might have over deep brain stimulation, Dr. Michael Hutchinson of New York University, wrote in an accompanying editorial. The added value of the study is that the placebo effect is not large enough to explain the benefits of gene therapy seen in open-label surgical trials, he said (Lancet Neurol. 2011 March 17 [doi:10.1016/S1474-4422(11)70041-2]).

A separate investigational gene therapy treatment for Parkinson's disease, called CERE-120, proved to be safe but lacked efficacy in a recent randomized, sham-controlled, phase II trial that was sponsored by Ceregene Inc. (Lancet Neurol. 2010;9:1164-72). The investigators of that trial blamed its results on the failed delivery of the therapy (consisting of the AAV2 viral vector and the gene for neurturin, a member of the same protein family as glial-derived neurotrophic factor) to dopaminergic neurons.

In the trial, AAV2-neurturin was injected into an area of the brain called the putamen in patients with Parkinson's disease, where the nerve terminals of degenerating dopaminergic neurons reside. However, the investigators realized that neurturin was not being transported effectively to the cell bodies of the dopaminergic neurons, which reside in the substantia nigra (Mov. Disord. 2011;26:27-36).

A new treatment protocol that delivers a larger dose of AAV2-neurturin to the putamen, as well as directly to the substantia nigra, is currently being tested in a new randomized, sham-controlled, phase II trial of approximately 52 Parkinson's disease patients at 11 U.S. centers. The new treatment protocol was successfully given to six patients with Parkinson's disease in a phase I trial and has not been associated with any serious adverse events after 7-13 months of follow-up, according to Ceregene.

The new phase II trial of AAV2-neurturin is partially funded by the Michael J. Fox Foundation.

Jeff Evans contributed to this report.

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services.

About 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, wrote the authors of the report, “Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap.”

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults in this age group said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. About 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions such as promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual. Screening and counseling for alcohol misuse, zoster vaccination, aspirin use, blood pressure, cervical cancer, depression, and obesity also are recommended.

To view the full report, go to www.cdc.gov/Features/PreventiveServices

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services.

About 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, wrote the authors of the report, “Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap.”

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults in this age group said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. About 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions such as promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual. Screening and counseling for alcohol misuse, zoster vaccination, aspirin use, blood pressure, cervical cancer, depression, and obesity also are recommended.

To view the full report, go to www.cdc.gov/Features/PreventiveServices

Millions of Americans aged 65 years and older are not receiving potentially lifesaving preventive services, according to a report issued by the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services.

About 85% of flu-related deaths and 63% of flu-related hospitalizations occur in adults aged 65 years and older. Data have shown that the pneumococcal vaccine is a cost-effective way to improve survival and reduce hospital stay in older adults with community-acquired pneumonia, wrote the authors of the report, “Enhancing Use of Clinical Preventive Services Among Older Adults: Closing the Gap.”

However, in 2009, more than 31% of older adults had not received an influenza vaccination in the past year, while more than 33% reported that they had never received a pneumococcal vaccination.

The report included eight indicators to measure the use of clinical preventive health services by U.S. adults aged 65 years and older: influenza vaccination; pneumococcal vaccination; counseling for smoking cessation; and screening for breast cancer, colorectal cancer, diabetes, lipid disorders, and osteoporosis.

Breast cancer screening and cholesterol screening were the most widely used services. Only 17% of women aged 65 and older reported not receiving breast cancer screening in the past 2 years, while only 5% of adults in this age group said they had not had blood cholesterol screening in the past 5 years.

The report also highlighted ethnic disparities in many of the preventive services for older adults. Approximately 49% of Asian/Pacific Islanders and 47% of Hispanics in the United States reported that they had not undergone colorectal cancer screening, compared with 37% of blacks, 35% of American Indians/Alaska Natives, and 34% of whites. About 51% of Hispanics, 47% of blacks and Asian/Pacific Islanders, and 36% of American Indians/Alaska Natives reported never receiving a pneumococcal vaccine, compared with 30% of whites.

The report recommended interventions such as promoting annual wellness visits, reducing barriers to preventive care services, and tailoring preventive health messages to the needs of each individual. Screening and counseling for alcohol misuse, zoster vaccination, aspirin use, blood pressure, cervical cancer, depression, and obesity also are recommended.

To view the full report, go to www.cdc.gov/Features/PreventiveServices

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

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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.