Mary Ann Moon

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as "the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor." The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

"This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients," Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. "Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing," the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Physicians should strongly consider evaluating cirrhosis patients specifically for hepatic encephalopathy, because this neurologic disorder can be difficult to detect but can have a substantial impact on driving ability, Dr. Stanley Martin Cohen and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

In addition, physicians are potentially liable for any injury that may stem from this medical impairment, the authors wrote (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.002]).

In patients with advanced liver disease, hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities, from overt mental and neurologic symptoms to occult impairment. Minimal HE can be overlooked on standard neurologic assessments, and "diagnosis is only possible by using specialized psychometric and neurophysiological measures," the researchers said.

In one study, only 28% of hepatologists responding to a poll said they tested most of their cirrhotic patients for minimal HE, even though it is estimated to occur in up to 80% of cirrhosis patients.

Many studies have demonstrated that patients with minimal HE have more motor vehicle accidents and traffic violations than do people without the disorder. Between 45% and 61% of patients with minimal HE in various studies have been judged unfit to drive when tested, said Dr. Cohen of Loyola University, Maywood, Ill., and his associates.

They investigated each state’s laws and requirements for reporting of potentially impaired drivers and found that no states specifically addressed HE or impairment related to advanced liver disease. Moreover, the definition of "medically impaired" varied substantially from state to state.

Only six states – California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania – had laws requiring physicians to report medically impaired drivers to the motor vehicle department. All six provided physicians with legal immunity in such cases, so that they could not be charged with violating the patient’s right to privacy for making such reports.

Another 35 states (70%) had statutes allowing but not requiring physicians to report medically impaired drivers, but only 24 of these provided physicians with legal immunity for doing so.

The remaining nine states – Alaska, Hawaii, Massachusetts, Mississippi, South Carolina, Tennessee, Vermont, Washington, and Wyoming – had no statutes addressing physician reporting of medically impaired drivers, and only one of these nine provided physicians with legal immunity.

The investigators also reviewed several legal databases, legal journals, and case records from federal and state courts, and found that so far, there have been no completed lawsuits in which a physician was cited for failure to warn patients not to drive or for failure to diagnose HE that subsequently caused a motor vehicle accident. There also have been no completed lawsuits to date against patients with HE for causing an accident while operating a motor vehicle.

However, this review encompassed only cases that were adjudicated in the courts; information on lawsuits settled out of court was not available, they noted.

"We believe that it would be prudent for society to consider a recommendation to restrict the driving privileges of patients with any degree of HE," Dr. Cohen and his colleagues said.

The physician’s role would be to identify and report such patients to the proper governmental agency, which would then conduct a driving evaluation. "Until society and the legislature write the definitive laws determining individual rights versus public safety, the onus of responsibility for identifying potentially hazardous drivers (and the associated liability) might still lie with the physician," the authors noted.

The researchers cautioned that even in the few places where such laws already exist, they are difficult to enforce, so reporting is "suboptimal." One study showed that 86% of physicians in California, where such reporting is mandatory, "never" or "occasionally" did so. Only 12% of the physicians in that survey had actually read the laws.

The authors disclosed no conflicts of interest.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Among patients who have witnessed an out-of-hospital cardiac arrest, the proportion with a "shockable" arrhythmia is markedly higher in public settings (60%) than in home settings (35%), according to a prospective cohort study reported in the Jan. 27 issue of the New England Journal of Medicine.

The reason for this discrepancy is not yet clear, but the implication is that the usefulness of resuscitation strategies might depend on the location where the cardiac arrest occurs, said Dr. Myron L. Weisfeldt of Johns Hopkins University, Baltimore, and his associates.

Thirty years ago, 70% of witnessed out-of-hospital cardiac arrests were characterized by so-called shockable arrhythmias – ventricular fibrillation or pulseless ventricular tachycardia that are amenable to treatment with an automated external defibrillator (AED). That rate has dropped dramatically and now stands at only 23%.

The use of AEDs by laypersons in public settings is known to improve survival, but such use in residential settings does not. To determine whether this discrepancy is related to the prevalence of shockable rhythms in these locations, Dr. Weisfeldt and his colleagues analyzed data from a population-based emergency medical services registry of out-of-hospital cardiac arrests.

The prospective, multicenter cohort study involved 12,930 adults treated by 208 EMS agencies at seven U.S. and three Canadian sites for nontraumatic cardiac arrest in which external defibrillation or chest compressions were attempted.

Ventricular fibrillation or pulseless ventricular tachycardia occurred in 3,336 cases, for an overall frequency of 26%.

A total of 3,451 patients had bystander-witnessed cardiac arrest in the home, of which 1,193 (35%) had initial shockable arrhythmias when EMS arrived and applied AEDs. In contrast, 600 of the 1,003 patients (60%) whose cardiac arrest occurred in public had shockable arrhythmias when EMS arrived.

Similarly, when an AED was applied by a lay bystander before EMS arrival, only 36% of the patients in home settings had a shockable rhythm, compared with 79% of those in public settings.

As would be expected with these findings, the rates of survival to hospital discharge reflected this discrepancy: When an AED was applied by a bystander in a public location, survival was 34%, but when the device was applied by a bystander in a home, survival was only 12%, the investigators said (N. Engl. J. Med. 2011 Jan. 27;364:313-21).

"Although the median time from the 911 call to EMS arrival was modestly longer for bystander-witnessed cardiac arrests at home than for those in public, the EMS response times were less than 7 minutes for more than 75% of the patients in both locations," they noted.

Thus, "it does not seem likely that the much lower frequency of ventricular fibrillation or pulseless ventricular tachycardia observed after cardiac arrest in the home would be accounted for by differences in EMS response time or other delays in the case of home-witnessed arrests," Dr. Weisfeldt and his associates said.

Studies in Japan and Denmark also have found this discrepancy between home and public settings. Although the reason is not yet clear, one possible explanation is that patients who have a cardiac arrest at home are typically older and more likely to have comorbidities that limit their outside activities. Thus, the location of the cardiac arrest might be a surrogate marker for underlying disease severity, the researchers said.

Their findings suggest that AEDs and the training of lay responders in their use should be targeted at public rather than home settings. In the home, prompt, bystander-delivered CPR or compression-only CPR might save more lives than "the widespread deployment of AEDs," they added.

This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the U.S. Army Medical Research and Materiel Command, the Canadian Institutes of Health Research–Institute of Circulatory and Respiratory Health, the American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Dr. Weisfeldt reported receiving royalties from a patent for a pacemaker. His associates reported ties to Medtronic, Jolife, Philips, and Physio-Control.

Undergoing induced abortion was not associated with the later development of psychiatric problems, according to a report in the Jan. 27 issue of the New England Journal of Medicine.

In a population-based cohort study of more than 365,000 Danish women who became pregnant between 1995 and 2007, the rate of first-time contact with a psychiatric caregiver was no different in the year following a first-trimester induced abortion than it was during the year preceding the abortion, said Trine Munk-Olsen, Ph.D., of the National Center for Register-Based Research at Aarhus University, Denmark, and her associates.

The investigators undertook this study because previous studies of the issue "have had methodologic limitations, including small and self-selected study samples, low response rates and high dropout rates during the follow-up period, lack of control for potential confounders, and inadequate measures of exposure and outcome variables," they noted.

Their study avoided these limitations by relying on national registry data. Induced abortions are legal in Denmark and are tracked in the national health care registry, as are inpatient and outpatient contacts at psychiatric facilities.

The study included 365,550 Danish women who had no history of mental disorders and who had either a first childbirth or a first-ever first-trimester induced abortion between 1995 and 2007.

Among the 84,620 of these subjects who had a first-trimester induced abortion, the rate of a first inpatient or outpatient psychiatric contact was 1.5% during the following year, which was not significantly different from the 1.0% rate during the 9 months preceding the procedure.

The incidences of psychiatric contacts were 14.6/1,000 person-years before the induced abortion and 15.2/1,000 person-years afterward, a nonsignificant difference, Dr. Munk-Olsen and her associates wrote (N. Engl. J. Med. 2011;364:332-9).

"We performed additional analyses to assess whether the results differed on the basis of the subgroup of mental disorders," but they did not, the researchers said. The findings refute the contention that "there is an overall increased risk of mental disorders after first-trimester induced abortion."

Of interest was another finding that, during the same interval, when 280,930 women gave birth to their first live-born child, the rate of first-time psychiatric contact rose significantly from 0.3% in the year before delivery to 0.7% in the year following delivery. The incidences of psychiatric contacts were 3.9/1,000 person-years before childbirth and a significantly higher 6.7/1,000 person-years after childbirth. Thus, childbirth is related to a significant increase in psychiatric consultations, while induced abortion is not.

Although the rate of psychiatric contact was higher among women who had induced abortions than among those who gave birth, those rates were similarly discrepant before the pregnancies occurred. "This suggests that any propensity toward mental health disorders in women who have induced abortions predates the abortion and indeed may make termination of the pregnancy more likely," Dr. Munk-Olsen and her colleagues said.

"This finding underscores the potential bias of direct comparisons of rates of mental health problems between women who have undergone abortion and those who have given birth," they noted.

One such study found a 30% relative increase in the rate of mental disorders among women having abortions, compared with women not having abortions. "However, the study was performed in New Zealand, where the majority of abortions are authorized on the basis of mental health indications. This restriction in the availability of abortions can introduce bias, since mental health problems observed after an abortion may reflect conditions and characteristics predating the abortion rather than resulting from the abortion," the investigators wrote.

This study was supported by grants from the Susan Thompson Buffett Foundation and the Danish Medical Research Council. One of Dr. Munk-Olsen’s associates reported ties to Bayer Schering Pharma.

Undergoing induced abortion was not associated with the later development of psychiatric problems, according to a report in the Jan. 27 issue of the New England Journal of Medicine.

In a population-based cohort study of more than 365,000 Danish women who became pregnant between 1995 and 2007, the rate of first-time contact with a psychiatric caregiver was no different in the year following a first-trimester induced abortion than it was during the year preceding the abortion, said Trine Munk-Olsen, Ph.D., of the National Center for Register-Based Research at Aarhus University, Denmark, and her associates.

The investigators undertook this study because previous studies of the issue "have had methodologic limitations, including small and self-selected study samples, low response rates and high dropout rates during the follow-up period, lack of control for potential confounders, and inadequate measures of exposure and outcome variables," they noted.

Their study avoided these limitations by relying on national registry data. Induced abortions are legal in Denmark and are tracked in the national health care registry, as are inpatient and outpatient contacts at psychiatric facilities.

The study included 365,550 Danish women who had no history of mental disorders and who had either a first childbirth or a first-ever first-trimester induced abortion between 1995 and 2007.

Among the 84,620 of these subjects who had a first-trimester induced abortion, the rate of a first inpatient or outpatient psychiatric contact was 1.5% during the following year, which was not significantly different from the 1.0% rate during the 9 months preceding the procedure.

The incidences of psychiatric contacts were 14.6/1,000 person-years before the induced abortion and 15.2/1,000 person-years afterward, a nonsignificant difference, Dr. Munk-Olsen and her associates wrote (N. Engl. J. Med. 2011;364:332-9).

"We performed additional analyses to assess whether the results differed on the basis of the subgroup of mental disorders," but they did not, the researchers said. The findings refute the contention that "there is an overall increased risk of mental disorders after first-trimester induced abortion."

Of interest was another finding that, during the same interval, when 280,930 women gave birth to their first live-born child, the rate of first-time psychiatric contact rose significantly from 0.3% in the year before delivery to 0.7% in the year following delivery. The incidences of psychiatric contacts were 3.9/1,000 person-years before childbirth and a significantly higher 6.7/1,000 person-years after childbirth. Thus, childbirth is related to a significant increase in psychiatric consultations, while induced abortion is not.

Although the rate of psychiatric contact was higher among women who had induced abortions than among those who gave birth, those rates were similarly discrepant before the pregnancies occurred. "This suggests that any propensity toward mental health disorders in women who have induced abortions predates the abortion and indeed may make termination of the pregnancy more likely," Dr. Munk-Olsen and her colleagues said.

"This finding underscores the potential bias of direct comparisons of rates of mental health problems between women who have undergone abortion and those who have given birth," they noted.

One such study found a 30% relative increase in the rate of mental disorders among women having abortions, compared with women not having abortions. "However, the study was performed in New Zealand, where the majority of abortions are authorized on the basis of mental health indications. This restriction in the availability of abortions can introduce bias, since mental health problems observed after an abortion may reflect conditions and characteristics predating the abortion rather than resulting from the abortion," the investigators wrote.

This study was supported by grants from the Susan Thompson Buffett Foundation and the Danish Medical Research Council. One of Dr. Munk-Olsen’s associates reported ties to Bayer Schering Pharma.

Undergoing induced abortion was not associated with the later development of psychiatric problems, according to a report in the Jan. 27 issue of the New England Journal of Medicine.

In a population-based cohort study of more than 365,000 Danish women who became pregnant between 1995 and 2007, the rate of first-time contact with a psychiatric caregiver was no different in the year following a first-trimester induced abortion than it was during the year preceding the abortion, said Trine Munk-Olsen, Ph.D., of the National Center for Register-Based Research at Aarhus University, Denmark, and her associates.

The investigators undertook this study because previous studies of the issue "have had methodologic limitations, including small and self-selected study samples, low response rates and high dropout rates during the follow-up period, lack of control for potential confounders, and inadequate measures of exposure and outcome variables," they noted.

Their study avoided these limitations by relying on national registry data. Induced abortions are legal in Denmark and are tracked in the national health care registry, as are inpatient and outpatient contacts at psychiatric facilities.

The study included 365,550 Danish women who had no history of mental disorders and who had either a first childbirth or a first-ever first-trimester induced abortion between 1995 and 2007.

Among the 84,620 of these subjects who had a first-trimester induced abortion, the rate of a first inpatient or outpatient psychiatric contact was 1.5% during the following year, which was not significantly different from the 1.0% rate during the 9 months preceding the procedure.

The incidences of psychiatric contacts were 14.6/1,000 person-years before the induced abortion and 15.2/1,000 person-years afterward, a nonsignificant difference, Dr. Munk-Olsen and her associates wrote (N. Engl. J. Med. 2011;364:332-9).

"We performed additional analyses to assess whether the results differed on the basis of the subgroup of mental disorders," but they did not, the researchers said. The findings refute the contention that "there is an overall increased risk of mental disorders after first-trimester induced abortion."

Of interest was another finding that, during the same interval, when 280,930 women gave birth to their first live-born child, the rate of first-time psychiatric contact rose significantly from 0.3% in the year before delivery to 0.7% in the year following delivery. The incidences of psychiatric contacts were 3.9/1,000 person-years before childbirth and a significantly higher 6.7/1,000 person-years after childbirth. Thus, childbirth is related to a significant increase in psychiatric consultations, while induced abortion is not.

Although the rate of psychiatric contact was higher among women who had induced abortions than among those who gave birth, those rates were similarly discrepant before the pregnancies occurred. "This suggests that any propensity toward mental health disorders in women who have induced abortions predates the abortion and indeed may make termination of the pregnancy more likely," Dr. Munk-Olsen and her colleagues said.

"This finding underscores the potential bias of direct comparisons of rates of mental health problems between women who have undergone abortion and those who have given birth," they noted.

One such study found a 30% relative increase in the rate of mental disorders among women having abortions, compared with women not having abortions. "However, the study was performed in New Zealand, where the majority of abortions are authorized on the basis of mental health indications. This restriction in the availability of abortions can introduce bias, since mental health problems observed after an abortion may reflect conditions and characteristics predating the abortion rather than resulting from the abortion," the investigators wrote.

This study was supported by grants from the Susan Thompson Buffett Foundation and the Danish Medical Research Council. One of Dr. Munk-Olsen’s associates reported ties to Bayer Schering Pharma.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.

Stroke occurred more often postoperatively than intraoperatively in more than 45,000 patients who underwent coronary artery bypass grafting at a single center during a 30-year period, according to a report in the Jan. 26 issue of JAMA.

The overall incidence of CABG-related stroke also declined since the late 1980s, even though the risk profiles of patients have been worsening at the same time, with the procedure being performed in recent years in more patients who have hypertension, diabetes, and even a history of stroke, Dr. Khaldoun G. Tarakji and his associates at the Cleveland Clinic reported (JAMA 2011:305:381-90).

They studied the timing of CABG-related stroke because few studies have examined the issue and because "understanding the risk factors specific to the timing ... should be beneficial in identifying the cause of the stroke and developing preoperative, operative, and postoperative strategies to predict and prevent stroke."

Dr. Tarakji and his colleagues reviewed 45,432 consecutive cases of CABG at their center during 1982-2010. Overall, 1.6% of patients developed perioperative stroke.

After peaking at 2.6% in 1988, perioperative stroke declined thereafter by 4.7% per year. "This is most likely the result of improving preoperative assessment, intraoperative anesthetic and surgical techniques, and postoperative care," they noted.

Approximately three-fifths of the patients who developed stroke did so postoperatively, with the incidence peaking at day 2 and reverting to a constant hazard of 0.05% by day 6.

"The inflammatory process and hypercoagulability after surgery might provide some explanation for this peak. Identifying the etiology of this postoperative risk factor for stroke may lead to better strategies to prevent it, whether through more aggressive use of antithrombotic and antiplatelet agents, prophylactic prevention of atrial fibrillation, or both," the investigators wrote.

Surprisingly, new-onset postoperative atrial fibrillation did not raise the risk of postoperative stroke.

"To treat new-onset atrial fibrillation, we initially try early medical conversion or electroconversion and, if AF recurs or is persistent, rate control, and anticoagulation. This strategy appears to be associated with not only preventing an anticipated increased risk of postoperative stroke but perhaps [also] with actually lowering the risk," they noted.

Different surgical techniques carried different risks for intraoperative stroke. "We found off-pump CABG and on-pump beating-heart CABG to be associated with the lowest risk of intraoperative stroke [0.14% and 0%, respectively], on-pump arrested-heart CABG with slightly higher risk [0.50%], and on-pump CABG with hypothermic systemic circulatory arrest with the greatest risk [5.3%]," Dr. Tarakji and his associates wrote.

"Both off-pump CABG and on-pump beating-heart CABG can be performed with minimal aortic manipulation, and therefore they likely lower the risk of stroke by decreasing the risk of aortic atherosclerotic embolization." However, this potential benefit "must be weighed against the greater risk of incomplete revascularization, lower graft patency, and worse 1-year outcomes reported for patients undergoing off-pump CABG."

Intraoperative stroke risk increased with advancing age when surgeons used on-pump arrested-heart CABG or on-pump CABG with hypothermic circulatory arrest, but not when they used off-pump CABG or on-pump beating-heart CABG.

"In patients at high risk of intraoperative stroke, such as the elderly or those with aortic arteriosclerosis, off-pump CABG or on-pump beating-heart CABG with no or minimal aortic manipulation may be best. However, in patients at low risk of stroke, such as those without aortic arteriosclerosis and minimal arteriosclerotic burden, on-pump CABG is likely the best option to provide optimal surgical revascularization and minimal risk of stroke," they wrote.

The investigators cautioned that their data were drawn from a single academic medical center and thus may not be generalizable to all U.S. practice.

The study was funded by the Cleveland Clinic. One of Dr. Tarakji’s coauthors reported receiving honoraria from Medtronic.