Mary Ann Moon

Patients who did not undergo defibrillation testing during the insertion of their first implantable cardioverter defibrillator had outcomes similar to those who did undergo defibrillation testing of the device in the largest study to date comparing the two approaches, which was reported online August 1 in the Journal of the American College of Cardiology.

Photo CarolinaSmith/iStockphoto.com

This finding supports a strategy of omitting defibrillation testing in most such patients – a strategy that clinicians are already adopting in increasing numbers, said Dr. Michele Brignole, chief of cardiology at Ospedale del Tigullio, Lavagna, Italy, and his associates.

Defibrillation testing has been considered a standard procedure at ICD insertion "to ensure adequate sensing of ventricular fibrillation, appropriate connection of high-voltage electrodes, and the ability of the device to terminate VF with a shock. Nevertheless, implant techniques and technology have evolved in recent years, and deviations from this clinical practice are frequent," the investigators noted.

To assess the safety of omitting this step in the implantation process, Dr. Brignole and his colleagues performed SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation), a prospective study of 2,120 consecutive procedures in adults at 41 Italian medical centers. The treating physicians were allowed either to perform or not perform defibrillation testing according to their standard practice; patients were followed for 2 years.

The frequency of performing defibrillation testing varied widely among the different medical centers, with some of them conducting the test in all patients and others doing so in no patients. Overall, 836 study subjects (39%) underwent defibrillation testing during insertion of their ICD, and the remaining 1,284 (61%) did not.

The primary end point was a composite of severe implant-related complications periprocedurally plus serious events during follow-up, such as sudden cardiac death or resuscitation after delivery of ineffective but appropriate ICD shocks.

This end point was reached in 18 patients who underwent defibrillation testing and 16 who did not. The estimated yearly incidence of this composite end point was 1.15% with defibrillation testing and 0.68% without it, a "negligible" difference.

In addition, 2-year all-cause mortality was not significantly lower for patients who underwent defibrillation testing (12.9%) than for those who did not (14.6%).

During follow-up, the devices delivered appropriate and effective shocks in a similar proportion of patients in the two study groups.

These findings indicate that "the clinical relevance of defibrillation testing is limited, thus supporting the practice of omitting [it] at implant," Dr. Brignole and his associates said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.05.014]).

ICD recipients "are very well protected from sudden cardiac death irrespective of performing defibrillation testing or not," the authors said. Moreover, performing defibrillation testing is not likely to decrease the rate of sudden cardiac death to a clinically relevant degree, below the already low 1% rate observed in this study population, they added.

The strengths of this study included its large population that represented the general ICD population in Western countries, its very low (3%) dropout rate, and the use of any commercially available ICD devices.

However, the study was limited in that the unexpectedly low incidence of sudden cardiac death may have been insufficient to show a true difference between the two study groups.

The observational design of SAFE-ICD, unlike that of a randomized clinical trial, "does not allow us to draw a definitive conclusion" as to the safety of omitting defibrillation testing. But there is such a large, prospective, multicenter, randomized clinical trial – SIMPLE (Shockless Implant Evaluation), taking place now – that should provide a definitive answer, the researchers said.

This study was funded by Boston Scientific. One of Dr. Brignole’s associates is an employee of Boston Scientific, and others reported ties to Boston Scientific and Medtronic. Dr. Estes reported ties to Boston Scientific, Medtronic, and St. Jude Medical.

Patients who did not undergo defibrillation testing during the insertion of their first implantable cardioverter defibrillator had outcomes similar to those who did undergo defibrillation testing of the device in the largest study to date comparing the two approaches, which was reported online August 1 in the Journal of the American College of Cardiology.

Photo CarolinaSmith/iStockphoto.com

This finding supports a strategy of omitting defibrillation testing in most such patients – a strategy that clinicians are already adopting in increasing numbers, said Dr. Michele Brignole, chief of cardiology at Ospedale del Tigullio, Lavagna, Italy, and his associates.

Defibrillation testing has been considered a standard procedure at ICD insertion "to ensure adequate sensing of ventricular fibrillation, appropriate connection of high-voltage electrodes, and the ability of the device to terminate VF with a shock. Nevertheless, implant techniques and technology have evolved in recent years, and deviations from this clinical practice are frequent," the investigators noted.

To assess the safety of omitting this step in the implantation process, Dr. Brignole and his colleagues performed SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation), a prospective study of 2,120 consecutive procedures in adults at 41 Italian medical centers. The treating physicians were allowed either to perform or not perform defibrillation testing according to their standard practice; patients were followed for 2 years.

The frequency of performing defibrillation testing varied widely among the different medical centers, with some of them conducting the test in all patients and others doing so in no patients. Overall, 836 study subjects (39%) underwent defibrillation testing during insertion of their ICD, and the remaining 1,284 (61%) did not.

The primary end point was a composite of severe implant-related complications periprocedurally plus serious events during follow-up, such as sudden cardiac death or resuscitation after delivery of ineffective but appropriate ICD shocks.

This end point was reached in 18 patients who underwent defibrillation testing and 16 who did not. The estimated yearly incidence of this composite end point was 1.15% with defibrillation testing and 0.68% without it, a "negligible" difference.

In addition, 2-year all-cause mortality was not significantly lower for patients who underwent defibrillation testing (12.9%) than for those who did not (14.6%).

During follow-up, the devices delivered appropriate and effective shocks in a similar proportion of patients in the two study groups.

These findings indicate that "the clinical relevance of defibrillation testing is limited, thus supporting the practice of omitting [it] at implant," Dr. Brignole and his associates said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.05.014]).

ICD recipients "are very well protected from sudden cardiac death irrespective of performing defibrillation testing or not," the authors said. Moreover, performing defibrillation testing is not likely to decrease the rate of sudden cardiac death to a clinically relevant degree, below the already low 1% rate observed in this study population, they added.

The strengths of this study included its large population that represented the general ICD population in Western countries, its very low (3%) dropout rate, and the use of any commercially available ICD devices.

However, the study was limited in that the unexpectedly low incidence of sudden cardiac death may have been insufficient to show a true difference between the two study groups.

The observational design of SAFE-ICD, unlike that of a randomized clinical trial, "does not allow us to draw a definitive conclusion" as to the safety of omitting defibrillation testing. But there is such a large, prospective, multicenter, randomized clinical trial – SIMPLE (Shockless Implant Evaluation), taking place now – that should provide a definitive answer, the researchers said.

This study was funded by Boston Scientific. One of Dr. Brignole’s associates is an employee of Boston Scientific, and others reported ties to Boston Scientific and Medtronic. Dr. Estes reported ties to Boston Scientific, Medtronic, and St. Jude Medical.

Patients who did not undergo defibrillation testing during the insertion of their first implantable cardioverter defibrillator had outcomes similar to those who did undergo defibrillation testing of the device in the largest study to date comparing the two approaches, which was reported online August 1 in the Journal of the American College of Cardiology.

Photo CarolinaSmith/iStockphoto.com

This finding supports a strategy of omitting defibrillation testing in most such patients – a strategy that clinicians are already adopting in increasing numbers, said Dr. Michele Brignole, chief of cardiology at Ospedale del Tigullio, Lavagna, Italy, and his associates.

Defibrillation testing has been considered a standard procedure at ICD insertion "to ensure adequate sensing of ventricular fibrillation, appropriate connection of high-voltage electrodes, and the ability of the device to terminate VF with a shock. Nevertheless, implant techniques and technology have evolved in recent years, and deviations from this clinical practice are frequent," the investigators noted.

To assess the safety of omitting this step in the implantation process, Dr. Brignole and his colleagues performed SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation), a prospective study of 2,120 consecutive procedures in adults at 41 Italian medical centers. The treating physicians were allowed either to perform or not perform defibrillation testing according to their standard practice; patients were followed for 2 years.

The frequency of performing defibrillation testing varied widely among the different medical centers, with some of them conducting the test in all patients and others doing so in no patients. Overall, 836 study subjects (39%) underwent defibrillation testing during insertion of their ICD, and the remaining 1,284 (61%) did not.

The primary end point was a composite of severe implant-related complications periprocedurally plus serious events during follow-up, such as sudden cardiac death or resuscitation after delivery of ineffective but appropriate ICD shocks.

This end point was reached in 18 patients who underwent defibrillation testing and 16 who did not. The estimated yearly incidence of this composite end point was 1.15% with defibrillation testing and 0.68% without it, a "negligible" difference.

In addition, 2-year all-cause mortality was not significantly lower for patients who underwent defibrillation testing (12.9%) than for those who did not (14.6%).

During follow-up, the devices delivered appropriate and effective shocks in a similar proportion of patients in the two study groups.

These findings indicate that "the clinical relevance of defibrillation testing is limited, thus supporting the practice of omitting [it] at implant," Dr. Brignole and his associates said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.05.014]).

ICD recipients "are very well protected from sudden cardiac death irrespective of performing defibrillation testing or not," the authors said. Moreover, performing defibrillation testing is not likely to decrease the rate of sudden cardiac death to a clinically relevant degree, below the already low 1% rate observed in this study population, they added.

The strengths of this study included its large population that represented the general ICD population in Western countries, its very low (3%) dropout rate, and the use of any commercially available ICD devices.

However, the study was limited in that the unexpectedly low incidence of sudden cardiac death may have been insufficient to show a true difference between the two study groups.

The observational design of SAFE-ICD, unlike that of a randomized clinical trial, "does not allow us to draw a definitive conclusion" as to the safety of omitting defibrillation testing. But there is such a large, prospective, multicenter, randomized clinical trial – SIMPLE (Shockless Implant Evaluation), taking place now – that should provide a definitive answer, the researchers said.

This study was funded by Boston Scientific. One of Dr. Brignole’s associates is an employee of Boston Scientific, and others reported ties to Boston Scientific and Medtronic. Dr. Estes reported ties to Boston Scientific, Medtronic, and St. Jude Medical.

Endoscopic vein-graft harvesting was not associated with increased rates of death, myocardial infarction, or repeat revascularization in patients undergoing coronary artery bypass grafting, according to a database analysis of more than 200,000 patients. The study was requested and funded by the Food and Drug Administration and reported in the Aug. 1 issue of JAMA.

In 2009, an observational study of 3,000 CABG patients showed that endoscopic vein-graft harvesting carried a higher risk of mortality and graft failure than did open vein-graft harvesting. It was suggested that the endoscopic technique might cause more harm because it involved added vessel manipulation, venous stasis from the pressurized subcutaneous tunnel, and larger caliber vein-graft segments. In addition, other studies throughout the world showed conflicting results when comparing the two techniques.

In response, the FDA asked that the issue be further investigated using the massive Society of Thoracic Surgeons’ adult cardiac surgery database. By linking this information with data on long-term outcomes from the Centers for Medicare and Medicaid Services database, investigators were able to track outcomes in 235,394 patients who underwent primary isolated CABG at 934 sites during a 5-year period. They were followed for a median of 3 years.

Dr. Judson B. Williams of Duke Clinical Research Institute, Durham, N.C., and his associates found no significant difference between the two techniques of vein-graft harvesting in overall mortality. The cumulative rates of death were 13.2% in the 122,899 patients who had endoscopic vein-graft harvesting and 13.4% in the 112,495 who had open vein-graft harvesting.

In addition, the composite rate of death, MI, or repeat revascularization also was not significantly different between the two groups: 19.5% with endoscopic and 19.7% with open vein-graft harvesting, the investigators said (JAMA 2012;308:475-84).

The endoscopic technique carried a significantly lower rate of harvest site wound complications, as expected (3.0% vs. 3.6%).

The large study population allowed for further assessment of important subgroups of CABG patients. Again, there were no differences in outcomes between endoscopic and open techniques in the nearly 42,000 subjects with insulin-dependent diabetes, and no differences according to subjects’ body mass index. There also were no differences in outcomes according to the number of vein-grafts harvested.

The results of sensitivity analyses paralleled the main finding of the study. CABG patients undergoing endoscopic vein-graft harvesting showed the same long-term mortality and the same composite rate of death, MI, and revascularization as did those undergoing open vein-graft harvesting, but significantly lower rates of wound complications.

As with other studies of this controversial issue, this analysis was limited in that it "was unable to account for differences in conduit caliber between the endoscopic and open vein-graft harvesting groups, a potentially critical confounding variable" in comparing the two techniques, Dr. Williams and his associates said.

Another important limitation was the length of follow-up – only 3-years, since the STS database did not identify endoscopic harvesting before 2008.

In addition, "our observational study, as with previous studies, is unable to assess for particulars of technique such as carbon dioxide insufflations, use of electrocautery, or the experience of the endoscopic harvester," they added.

This study was funded by the Food and Drug Administration, the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Williams reported no financial conflicts of interest, and his associates reported numerous ties to industry sources.

Endoscopic vein-graft harvesting was not associated with increased rates of death, myocardial infarction, or repeat revascularization in patients undergoing coronary artery bypass grafting, according to a database analysis of more than 200,000 patients. The study was requested and funded by the Food and Drug Administration and reported in the Aug. 1 issue of JAMA.

In 2009, an observational study of 3,000 CABG patients showed that endoscopic vein-graft harvesting carried a higher risk of mortality and graft failure than did open vein-graft harvesting. It was suggested that the endoscopic technique might cause more harm because it involved added vessel manipulation, venous stasis from the pressurized subcutaneous tunnel, and larger caliber vein-graft segments. In addition, other studies throughout the world showed conflicting results when comparing the two techniques.

In response, the FDA asked that the issue be further investigated using the massive Society of Thoracic Surgeons’ adult cardiac surgery database. By linking this information with data on long-term outcomes from the Centers for Medicare and Medicaid Services database, investigators were able to track outcomes in 235,394 patients who underwent primary isolated CABG at 934 sites during a 5-year period. They were followed for a median of 3 years.

Dr. Judson B. Williams of Duke Clinical Research Institute, Durham, N.C., and his associates found no significant difference between the two techniques of vein-graft harvesting in overall mortality. The cumulative rates of death were 13.2% in the 122,899 patients who had endoscopic vein-graft harvesting and 13.4% in the 112,495 who had open vein-graft harvesting.

In addition, the composite rate of death, MI, or repeat revascularization also was not significantly different between the two groups: 19.5% with endoscopic and 19.7% with open vein-graft harvesting, the investigators said (JAMA 2012;308:475-84).

The endoscopic technique carried a significantly lower rate of harvest site wound complications, as expected (3.0% vs. 3.6%).

The large study population allowed for further assessment of important subgroups of CABG patients. Again, there were no differences in outcomes between endoscopic and open techniques in the nearly 42,000 subjects with insulin-dependent diabetes, and no differences according to subjects’ body mass index. There also were no differences in outcomes according to the number of vein-grafts harvested.

The results of sensitivity analyses paralleled the main finding of the study. CABG patients undergoing endoscopic vein-graft harvesting showed the same long-term mortality and the same composite rate of death, MI, and revascularization as did those undergoing open vein-graft harvesting, but significantly lower rates of wound complications.

As with other studies of this controversial issue, this analysis was limited in that it "was unable to account for differences in conduit caliber between the endoscopic and open vein-graft harvesting groups, a potentially critical confounding variable" in comparing the two techniques, Dr. Williams and his associates said.

Another important limitation was the length of follow-up – only 3-years, since the STS database did not identify endoscopic harvesting before 2008.

In addition, "our observational study, as with previous studies, is unable to assess for particulars of technique such as carbon dioxide insufflations, use of electrocautery, or the experience of the endoscopic harvester," they added.

This study was funded by the Food and Drug Administration, the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Williams reported no financial conflicts of interest, and his associates reported numerous ties to industry sources.

Endoscopic vein-graft harvesting was not associated with increased rates of death, myocardial infarction, or repeat revascularization in patients undergoing coronary artery bypass grafting, according to a database analysis of more than 200,000 patients. The study was requested and funded by the Food and Drug Administration and reported in the Aug. 1 issue of JAMA.

In 2009, an observational study of 3,000 CABG patients showed that endoscopic vein-graft harvesting carried a higher risk of mortality and graft failure than did open vein-graft harvesting. It was suggested that the endoscopic technique might cause more harm because it involved added vessel manipulation, venous stasis from the pressurized subcutaneous tunnel, and larger caliber vein-graft segments. In addition, other studies throughout the world showed conflicting results when comparing the two techniques.

In response, the FDA asked that the issue be further investigated using the massive Society of Thoracic Surgeons’ adult cardiac surgery database. By linking this information with data on long-term outcomes from the Centers for Medicare and Medicaid Services database, investigators were able to track outcomes in 235,394 patients who underwent primary isolated CABG at 934 sites during a 5-year period. They were followed for a median of 3 years.

Dr. Judson B. Williams of Duke Clinical Research Institute, Durham, N.C., and his associates found no significant difference between the two techniques of vein-graft harvesting in overall mortality. The cumulative rates of death were 13.2% in the 122,899 patients who had endoscopic vein-graft harvesting and 13.4% in the 112,495 who had open vein-graft harvesting.

In addition, the composite rate of death, MI, or repeat revascularization also was not significantly different between the two groups: 19.5% with endoscopic and 19.7% with open vein-graft harvesting, the investigators said (JAMA 2012;308:475-84).

The endoscopic technique carried a significantly lower rate of harvest site wound complications, as expected (3.0% vs. 3.6%).

The large study population allowed for further assessment of important subgroups of CABG patients. Again, there were no differences in outcomes between endoscopic and open techniques in the nearly 42,000 subjects with insulin-dependent diabetes, and no differences according to subjects’ body mass index. There also were no differences in outcomes according to the number of vein-grafts harvested.

The results of sensitivity analyses paralleled the main finding of the study. CABG patients undergoing endoscopic vein-graft harvesting showed the same long-term mortality and the same composite rate of death, MI, and revascularization as did those undergoing open vein-graft harvesting, but significantly lower rates of wound complications.

As with other studies of this controversial issue, this analysis was limited in that it "was unable to account for differences in conduit caliber between the endoscopic and open vein-graft harvesting groups, a potentially critical confounding variable" in comparing the two techniques, Dr. Williams and his associates said.

Another important limitation was the length of follow-up – only 3-years, since the STS database did not identify endoscopic harvesting before 2008.

In addition, "our observational study, as with previous studies, is unable to assess for particulars of technique such as carbon dioxide insufflations, use of electrocautery, or the experience of the endoscopic harvester," they added.

This study was funded by the Food and Drug Administration, the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Williams reported no financial conflicts of interest, and his associates reported numerous ties to industry sources.

Aerobic exercise for 90-120 minutes per week modestly reduces depressive symptoms in patients with heart failure, according to a report in the Aug. 1 issue of JAMA.

After 3 months of a supervised exercise program, patients who exercised showed a small but significant reduction in depression scores, compared with patients who received usual care. After an additional 9 months of home exercise, that difference persisted.

Photo © Dave/Fotolia.com

The difference was characterized as modest, "and the clinical significance of this small improvement is not known," said James A. Blumenthal, Ph.D., of Duke University, Durham, N.C., and his associates.

However, because the difference was consistent over a full year, it appears to be robust and "is likely to be associated with better social functioning and higher quality of life," they noted.

As many as 40% of patients with heart failure have been reported to have comorbid depression, and as many as 75% of heart failure patients have been reported to have elevated depressive symptoms. But few randomized trials have examined treatment of depression in this patient population.

HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise Training) found that adding exercise to usual care modestly reduced rates of death from any cause and hospitalization for any cause. Dr. Blumenthal and his colleagues reported on an ancillary study to HF-ACTION in which they further assessed the effects of exercise on depressive symptoms.

The study subjects were 2,322 patients whose HF failed to improve after at least 6 weeks of optimal therapy at 82 medical centers in the United States, Canada, and France. All the subjects had undergone exercise stress testing and had completed the Beck Depression Inventory II at baseline in 2003-2007. The median age was 59 years (range, 19-91 years).

The BDI-II is a self-reported measure of depressive symptoms with a possible score ranging from 0 (no depressive symptoms) to 63 (maximal depressive symptoms). A score of 14 or higher reflects clinically significant depressive symptoms. A total of 28% of the study subjects scored in this range at baseline.

A total of 1,164 subjects were randomly assigned to usual care (the control group) and 1,158 to usual care plus three supervised sessions per week on a treadmill or stationary cycle for 3 months. The exercise group was then given the exercise equipment of their choice to take home and was encouraged to increase to 90 min/week of exercise until they reached 1 year from baseline.

At 3 months, the mean BDI-II score was 8.95 for the exercise group and 9.70 for the control group. At 1 year, the mean scores were 8.86 and 9.54, respectively. Both of these differences are statistically significant, although small, the investigators said (JAMA 2012;308:465-74).

The results were more robust for the subgroup of 653 patients who scored 14 or higher on the BDI-II at baseline. At 3 months, the mean score in the exercise group was 16.66, compared with a mean score of 17.98 in the control group. At 1 year, the mean scores were 15.85 and 17.34, respectively.

In addition, the amount of exercise was inversely associated with the reduction in depressive symptoms. "Compared with a participant reporting no exercise, a participant reporting 90 minutes of exercise per week could be expected to have a 1.55-point lower BDI-II score at 3 months and a 1.67-point lower BDI-II score at 12 months," Dr. Blumenthal and his associates said.

Such a difference "is comparable with placebo-control trials involving patients with major depressive disorder," they added.

"We also observed that elevated depressive symptoms were associated with more than a 20% increase in risk for all-cause mortality and hospitalizations and that the increased risk was independent of antidepressant use and established risk factors in patients with heart failure, including age and disease severity.

"These data add to the evidence suggesting that elevated depressive symptoms, without necessarily meeting diagnostic criteria for major depressive disorder, are associated with increased risk for adverse clinical events," the researchers said.

The study findings also support the recent recommendation by the American Heart Association that all patients with cardiac disease be routinely assessed for depression, they added.

The study results also demonstrated that HF patients whose depression worsened over time were at particularly increased risk for hospitalization and death. This highlights the need to not only reduce depressive symptoms but also to prevent the worsening of existing depressive symptoms, Dr. Blumenthal and his colleagues said.

The study had two important limitations.

First, only about 40% of the patients assigned to exercise were fully adherent to the program and actually exercised 90-120 minutes per week. And 40%-50% of the patients in the control reported that they had actually exercised to some degree during follow-up. Such unintended crossover might have adversely affected the study findings.

Second, the study could not rule out the possibility that patients with more severe depressive symptoms were less likely to exercise, "so it is not clear whether exercise resulted in less depression or if depression resulted in less exercise," the researchers said.

Aerobic exercise for 90-120 minutes per week modestly reduces depressive symptoms in patients with heart failure, according to a report in the Aug. 1 issue of JAMA.

After 3 months of a supervised exercise program, patients who exercised showed a small but significant reduction in depression scores, compared with patients who received usual care. After an additional 9 months of home exercise, that difference persisted.

Photo © Dave/Fotolia.com

The difference was characterized as modest, "and the clinical significance of this small improvement is not known," said James A. Blumenthal, Ph.D., of Duke University, Durham, N.C., and his associates.

However, because the difference was consistent over a full year, it appears to be robust and "is likely to be associated with better social functioning and higher quality of life," they noted.

As many as 40% of patients with heart failure have been reported to have comorbid depression, and as many as 75% of heart failure patients have been reported to have elevated depressive symptoms. But few randomized trials have examined treatment of depression in this patient population.

HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise Training) found that adding exercise to usual care modestly reduced rates of death from any cause and hospitalization for any cause. Dr. Blumenthal and his colleagues reported on an ancillary study to HF-ACTION in which they further assessed the effects of exercise on depressive symptoms.

The study subjects were 2,322 patients whose HF failed to improve after at least 6 weeks of optimal therapy at 82 medical centers in the United States, Canada, and France. All the subjects had undergone exercise stress testing and had completed the Beck Depression Inventory II at baseline in 2003-2007. The median age was 59 years (range, 19-91 years).

The BDI-II is a self-reported measure of depressive symptoms with a possible score ranging from 0 (no depressive symptoms) to 63 (maximal depressive symptoms). A score of 14 or higher reflects clinically significant depressive symptoms. A total of 28% of the study subjects scored in this range at baseline.

A total of 1,164 subjects were randomly assigned to usual care (the control group) and 1,158 to usual care plus three supervised sessions per week on a treadmill or stationary cycle for 3 months. The exercise group was then given the exercise equipment of their choice to take home and was encouraged to increase to 90 min/week of exercise until they reached 1 year from baseline.

At 3 months, the mean BDI-II score was 8.95 for the exercise group and 9.70 for the control group. At 1 year, the mean scores were 8.86 and 9.54, respectively. Both of these differences are statistically significant, although small, the investigators said (JAMA 2012;308:465-74).

The results were more robust for the subgroup of 653 patients who scored 14 or higher on the BDI-II at baseline. At 3 months, the mean score in the exercise group was 16.66, compared with a mean score of 17.98 in the control group. At 1 year, the mean scores were 15.85 and 17.34, respectively.

In addition, the amount of exercise was inversely associated with the reduction in depressive symptoms. "Compared with a participant reporting no exercise, a participant reporting 90 minutes of exercise per week could be expected to have a 1.55-point lower BDI-II score at 3 months and a 1.67-point lower BDI-II score at 12 months," Dr. Blumenthal and his associates said.

Such a difference "is comparable with placebo-control trials involving patients with major depressive disorder," they added.

"We also observed that elevated depressive symptoms were associated with more than a 20% increase in risk for all-cause mortality and hospitalizations and that the increased risk was independent of antidepressant use and established risk factors in patients with heart failure, including age and disease severity.

"These data add to the evidence suggesting that elevated depressive symptoms, without necessarily meeting diagnostic criteria for major depressive disorder, are associated with increased risk for adverse clinical events," the researchers said.

The study findings also support the recent recommendation by the American Heart Association that all patients with cardiac disease be routinely assessed for depression, they added.

The study results also demonstrated that HF patients whose depression worsened over time were at particularly increased risk for hospitalization and death. This highlights the need to not only reduce depressive symptoms but also to prevent the worsening of existing depressive symptoms, Dr. Blumenthal and his colleagues said.

The study had two important limitations.

First, only about 40% of the patients assigned to exercise were fully adherent to the program and actually exercised 90-120 minutes per week. And 40%-50% of the patients in the control reported that they had actually exercised to some degree during follow-up. Such unintended crossover might have adversely affected the study findings.

Second, the study could not rule out the possibility that patients with more severe depressive symptoms were less likely to exercise, "so it is not clear whether exercise resulted in less depression or if depression resulted in less exercise," the researchers said.

Aerobic exercise for 90-120 minutes per week modestly reduces depressive symptoms in patients with heart failure, according to a report in the Aug. 1 issue of JAMA.

After 3 months of a supervised exercise program, patients who exercised showed a small but significant reduction in depression scores, compared with patients who received usual care. After an additional 9 months of home exercise, that difference persisted.

Photo © Dave/Fotolia.com

The difference was characterized as modest, "and the clinical significance of this small improvement is not known," said James A. Blumenthal, Ph.D., of Duke University, Durham, N.C., and his associates.

However, because the difference was consistent over a full year, it appears to be robust and "is likely to be associated with better social functioning and higher quality of life," they noted.

As many as 40% of patients with heart failure have been reported to have comorbid depression, and as many as 75% of heart failure patients have been reported to have elevated depressive symptoms. But few randomized trials have examined treatment of depression in this patient population.

HF-ACTION (Heart Failure–A Controlled Trial Investigating Outcomes of Exercise Training) found that adding exercise to usual care modestly reduced rates of death from any cause and hospitalization for any cause. Dr. Blumenthal and his colleagues reported on an ancillary study to HF-ACTION in which they further assessed the effects of exercise on depressive symptoms.

The study subjects were 2,322 patients whose HF failed to improve after at least 6 weeks of optimal therapy at 82 medical centers in the United States, Canada, and France. All the subjects had undergone exercise stress testing and had completed the Beck Depression Inventory II at baseline in 2003-2007. The median age was 59 years (range, 19-91 years).

The BDI-II is a self-reported measure of depressive symptoms with a possible score ranging from 0 (no depressive symptoms) to 63 (maximal depressive symptoms). A score of 14 or higher reflects clinically significant depressive symptoms. A total of 28% of the study subjects scored in this range at baseline.

A total of 1,164 subjects were randomly assigned to usual care (the control group) and 1,158 to usual care plus three supervised sessions per week on a treadmill or stationary cycle for 3 months. The exercise group was then given the exercise equipment of their choice to take home and was encouraged to increase to 90 min/week of exercise until they reached 1 year from baseline.

At 3 months, the mean BDI-II score was 8.95 for the exercise group and 9.70 for the control group. At 1 year, the mean scores were 8.86 and 9.54, respectively. Both of these differences are statistically significant, although small, the investigators said (JAMA 2012;308:465-74).

The results were more robust for the subgroup of 653 patients who scored 14 or higher on the BDI-II at baseline. At 3 months, the mean score in the exercise group was 16.66, compared with a mean score of 17.98 in the control group. At 1 year, the mean scores were 15.85 and 17.34, respectively.

In addition, the amount of exercise was inversely associated with the reduction in depressive symptoms. "Compared with a participant reporting no exercise, a participant reporting 90 minutes of exercise per week could be expected to have a 1.55-point lower BDI-II score at 3 months and a 1.67-point lower BDI-II score at 12 months," Dr. Blumenthal and his associates said.

Such a difference "is comparable with placebo-control trials involving patients with major depressive disorder," they added.

"We also observed that elevated depressive symptoms were associated with more than a 20% increase in risk for all-cause mortality and hospitalizations and that the increased risk was independent of antidepressant use and established risk factors in patients with heart failure, including age and disease severity.

"These data add to the evidence suggesting that elevated depressive symptoms, without necessarily meeting diagnostic criteria for major depressive disorder, are associated with increased risk for adverse clinical events," the researchers said.

The study findings also support the recent recommendation by the American Heart Association that all patients with cardiac disease be routinely assessed for depression, they added.

The study results also demonstrated that HF patients whose depression worsened over time were at particularly increased risk for hospitalization and death. This highlights the need to not only reduce depressive symptoms but also to prevent the worsening of existing depressive symptoms, Dr. Blumenthal and his colleagues said.

The study had two important limitations.

First, only about 40% of the patients assigned to exercise were fully adherent to the program and actually exercised 90-120 minutes per week. And 40%-50% of the patients in the control reported that they had actually exercised to some degree during follow-up. Such unintended crossover might have adversely affected the study findings.

Second, the study could not rule out the possibility that patients with more severe depressive symptoms were less likely to exercise, "so it is not clear whether exercise resulted in less depression or if depression resulted in less exercise," the researchers said.

A single clinical HPV DNA test can predict a woman’s cervical cancer risk for at least the next 18 years, identifying women who already have invasive cervical cancer and those whose HPV infections will develop into disease in the future, according to a report published online July 30 in the Journal of Clinical Oncology.

In contrast, Pap smears cannot predict clinically important disease beyond 1-2 years, said Dr. Philip E. Castle of the American Society for Clinical Pathology, Washington, and his associates.

"An HPV test provides greater reassurance against cervical intraepithelial neoplasia grade 3 and cervical cancer than Pap testing and thus might be used as the screen to rule out disease in healthy women, whereas Pap is useful as a secondary diagnostic test to identify HPV-positive women at immediate risk of" invasive cervical cancer, they noted.

Dr. Castle and his colleagues analyzed data from a Portland, Ore., cohort of 19,512 women who underwent routine cytologic screening when they were aged 16-94 years at baseline in 1989-1990. Cervicovaginal lavages were retrospectively tested for HPV DNA through a commercially available diagnostic test used routinely in clinical practice.

The study subjects were followed for approximately 18 years with annual Pap smears. A total of 199 cases of invasive cervical cancer (cervical intraepithelial neoplasia grade 3+) were diagnosed during this time; 396 cases of CIN2+ were detected.

A positive Pap smear at baseline strongly predicted cervical cancer within 2 years, but not beyond that point. In contrast, a positive HPV DNA test continued to predict cervical cancer until the end of the study.

For example, HPV-positive women were more likely to be diagnosed as having CIN2+ and CIN3+ 10-18 years after enrollment, compared with HPV-negative women, while women with a positive Pap smear result were not more likely to be diagnosed with CIN2+ or CIN3+ than women with a negative Pap test, Dr. Castle and his associates said (J. Clin. Oncol. 2012 July 30 [doi:10.1200/JCO.2011.38.8389]).

Similarly, a one-time negative HPV test at enrollment "provided greater reassurance over the 18-year follow-up" than a one-time negative Pap smear against CIN2+ (1.85% vs. 2.47%) and CIN3+ (0.90% vs. 1.27%), they said.

More cases of CIN2+ (215 vs. 136 cases) and CIN3+ (112 vs. 65 cases) developed after an HPV-positive result than after a positive Pap result. And among women who were positive for HPV DNA at baseline and who went on to develop CIN2+ or CIN3+, only half had positive Pap smear results.

These findings "provide additional support for the use of HPV testing in routine screening" in women 30 and older, Dr. Castle and his associates said.

Moreover, the results of other studies have suggested that HPV testing also may help identify women at risk for cervical adenocarcinoma in situ and invasive adenocarcinoma – two disorders that "are poorly detected by cytology-based screening alone," the investigators said.

This study was supported in part by the National Cancer Institute. Dr. Castle reported ties to Merck, Qiagen, and Roche, and his associate, Dr. Attila T. Lorincz, reported ties to Qiagen.

A single clinical HPV DNA test can predict a woman’s cervical cancer risk for at least the next 18 years, identifying women who already have invasive cervical cancer and those whose HPV infections will develop into disease in the future, according to a report published online July 30 in the Journal of Clinical Oncology.

In contrast, Pap smears cannot predict clinically important disease beyond 1-2 years, said Dr. Philip E. Castle of the American Society for Clinical Pathology, Washington, and his associates.

"An HPV test provides greater reassurance against cervical intraepithelial neoplasia grade 3 and cervical cancer than Pap testing and thus might be used as the screen to rule out disease in healthy women, whereas Pap is useful as a secondary diagnostic test to identify HPV-positive women at immediate risk of" invasive cervical cancer, they noted.

Dr. Castle and his colleagues analyzed data from a Portland, Ore., cohort of 19,512 women who underwent routine cytologic screening when they were aged 16-94 years at baseline in 1989-1990. Cervicovaginal lavages were retrospectively tested for HPV DNA through a commercially available diagnostic test used routinely in clinical practice.

The study subjects were followed for approximately 18 years with annual Pap smears. A total of 199 cases of invasive cervical cancer (cervical intraepithelial neoplasia grade 3+) were diagnosed during this time; 396 cases of CIN2+ were detected.

A positive Pap smear at baseline strongly predicted cervical cancer within 2 years, but not beyond that point. In contrast, a positive HPV DNA test continued to predict cervical cancer until the end of the study.

For example, HPV-positive women were more likely to be diagnosed as having CIN2+ and CIN3+ 10-18 years after enrollment, compared with HPV-negative women, while women with a positive Pap smear result were not more likely to be diagnosed with CIN2+ or CIN3+ than women with a negative Pap test, Dr. Castle and his associates said (J. Clin. Oncol. 2012 July 30 [doi:10.1200/JCO.2011.38.8389]).

Similarly, a one-time negative HPV test at enrollment "provided greater reassurance over the 18-year follow-up" than a one-time negative Pap smear against CIN2+ (1.85% vs. 2.47%) and CIN3+ (0.90% vs. 1.27%), they said.

More cases of CIN2+ (215 vs. 136 cases) and CIN3+ (112 vs. 65 cases) developed after an HPV-positive result than after a positive Pap result. And among women who were positive for HPV DNA at baseline and who went on to develop CIN2+ or CIN3+, only half had positive Pap smear results.

These findings "provide additional support for the use of HPV testing in routine screening" in women 30 and older, Dr. Castle and his associates said.

Moreover, the results of other studies have suggested that HPV testing also may help identify women at risk for cervical adenocarcinoma in situ and invasive adenocarcinoma – two disorders that "are poorly detected by cytology-based screening alone," the investigators said.

This study was supported in part by the National Cancer Institute. Dr. Castle reported ties to Merck, Qiagen, and Roche, and his associate, Dr. Attila T. Lorincz, reported ties to Qiagen.

A single clinical HPV DNA test can predict a woman’s cervical cancer risk for at least the next 18 years, identifying women who already have invasive cervical cancer and those whose HPV infections will develop into disease in the future, according to a report published online July 30 in the Journal of Clinical Oncology.

In contrast, Pap smears cannot predict clinically important disease beyond 1-2 years, said Dr. Philip E. Castle of the American Society for Clinical Pathology, Washington, and his associates.

"An HPV test provides greater reassurance against cervical intraepithelial neoplasia grade 3 and cervical cancer than Pap testing and thus might be used as the screen to rule out disease in healthy women, whereas Pap is useful as a secondary diagnostic test to identify HPV-positive women at immediate risk of" invasive cervical cancer, they noted.

Dr. Castle and his colleagues analyzed data from a Portland, Ore., cohort of 19,512 women who underwent routine cytologic screening when they were aged 16-94 years at baseline in 1989-1990. Cervicovaginal lavages were retrospectively tested for HPV DNA through a commercially available diagnostic test used routinely in clinical practice.

The study subjects were followed for approximately 18 years with annual Pap smears. A total of 199 cases of invasive cervical cancer (cervical intraepithelial neoplasia grade 3+) were diagnosed during this time; 396 cases of CIN2+ were detected.

A positive Pap smear at baseline strongly predicted cervical cancer within 2 years, but not beyond that point. In contrast, a positive HPV DNA test continued to predict cervical cancer until the end of the study.

For example, HPV-positive women were more likely to be diagnosed as having CIN2+ and CIN3+ 10-18 years after enrollment, compared with HPV-negative women, while women with a positive Pap smear result were not more likely to be diagnosed with CIN2+ or CIN3+ than women with a negative Pap test, Dr. Castle and his associates said (J. Clin. Oncol. 2012 July 30 [doi:10.1200/JCO.2011.38.8389]).

Similarly, a one-time negative HPV test at enrollment "provided greater reassurance over the 18-year follow-up" than a one-time negative Pap smear against CIN2+ (1.85% vs. 2.47%) and CIN3+ (0.90% vs. 1.27%), they said.

More cases of CIN2+ (215 vs. 136 cases) and CIN3+ (112 vs. 65 cases) developed after an HPV-positive result than after a positive Pap result. And among women who were positive for HPV DNA at baseline and who went on to develop CIN2+ or CIN3+, only half had positive Pap smear results.

These findings "provide additional support for the use of HPV testing in routine screening" in women 30 and older, Dr. Castle and his associates said.

Moreover, the results of other studies have suggested that HPV testing also may help identify women at risk for cervical adenocarcinoma in situ and invasive adenocarcinoma – two disorders that "are poorly detected by cytology-based screening alone," the investigators said.

This study was supported in part by the National Cancer Institute. Dr. Castle reported ties to Merck, Qiagen, and Roche, and his associate, Dr. Attila T. Lorincz, reported ties to Qiagen.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Among patients having their first episode of schizophrenia, suicidality is clearly associated with an altered sense of self, or what some experts have termed "self-disorders," a study of 49 adult patients shows.

Self-disorders are anomalous subjective experiences, described as "subtle disturbances of the person’s spontaneous experience of himself or herself as a vital subject naturally immersed in the world. As nonpsychotic distortions of self-awareness, they antedate the development of clearly delusional experiences and are highly prevalent in the prodromal and early psychotic phases" of schizophrenia, said Dr. Elisabeth Haug of the division of mental health, Innlandet Hospital Trust, Ottestad, Norway, and her associates.

The investigators assessed the relationship between self-disorders and suicidality in patients newly diagnosed as having schizophrenia spectrum disorder, because suicide risk is particularly high at this stage of the disease. They used data from the Norwegian Thematically Organized Psychosis study, which collected information from all mental health treatment facilities covering two counties with a pooled population of 375,000 people.

The study sample of 49 adults had been diagnosed over a 2-year period as having schizophrenia (38 patients), schizoaffective disorder (9 patients), or schizophreniform disorder (2 patients).

All the study subjects were assessed using the Examination of Anomalous Self Experience (EASE) manual, a 57-item questionnaire that addresses five domains of self-disorders: cognition and stream-of-consciousness, self-awareness and presence, bodily experiences, demarcation/transitivism, and existential reorientation. It includes questions such as "Have you ever felt as if thoughts in your head are not really belonging to you?" and solicits descriptions or examples from the patient rather than simple yes-or-no responses.

Each EASE interview took 30-90 minutes.

The investigators found that patients with newly diagnosed schizophrenia spectrum disorder also had high levels of suicidality and self-disorders (P = .036) and high levels of depression (P less than .001). "Our main finding is that of a clear association between current suicidality and [self-disorders], which appears to be mediated by depression," Dr. Haug and her colleagues said (Compr. Psychiatry 2012;53:456-60).

This result "strongly support[s] the role of self-disorders in the development of suicidal ideation and behavior in this patient group."

In a previous study, other researchers postulated that patients with self-disorders experience specific feelings of inferiority and solitude, which differ from "normal" feelings of low self-esteem or loneliness and represent "more fundamental feelings of being profoundly dissimilar to other people and thus unable to relate to others," Dr. Haug and her associates noted.

If self-disorders play a key role in the development of depression in early schizophrenia, it follows that they "could be a rational clinical target for the prevention of suicidality," they added.

The investigators noted: "Our cross-sectional design makes it difficult to rule out the possibility that depressed patients develop and report more [self-disorders]. Previous studies of the temporal relationship between these factors, however, indicate that the subjective experience of psychologic deficits in patients with schizophrenia prone to depression is high even when they are not depressed."

This study was supported by Innlandet Hospital Trust, South-East Health Authority, Eastern Norway Health Authority, and a European Union Marie Curie Fellowship. No financial conflicts of interest were reported.

Among patients having their first episode of schizophrenia, suicidality is clearly associated with an altered sense of self, or what some experts have termed "self-disorders," a study of 49 adult patients shows.

Self-disorders are anomalous subjective experiences, described as "subtle disturbances of the person’s spontaneous experience of himself or herself as a vital subject naturally immersed in the world. As nonpsychotic distortions of self-awareness, they antedate the development of clearly delusional experiences and are highly prevalent in the prodromal and early psychotic phases" of schizophrenia, said Dr. Elisabeth Haug of the division of mental health, Innlandet Hospital Trust, Ottestad, Norway, and her associates.

The investigators assessed the relationship between self-disorders and suicidality in patients newly diagnosed as having schizophrenia spectrum disorder, because suicide risk is particularly high at this stage of the disease. They used data from the Norwegian Thematically Organized Psychosis study, which collected information from all mental health treatment facilities covering two counties with a pooled population of 375,000 people.

The study sample of 49 adults had been diagnosed over a 2-year period as having schizophrenia (38 patients), schizoaffective disorder (9 patients), or schizophreniform disorder (2 patients).

All the study subjects were assessed using the Examination of Anomalous Self Experience (EASE) manual, a 57-item questionnaire that addresses five domains of self-disorders: cognition and stream-of-consciousness, self-awareness and presence, bodily experiences, demarcation/transitivism, and existential reorientation. It includes questions such as "Have you ever felt as if thoughts in your head are not really belonging to you?" and solicits descriptions or examples from the patient rather than simple yes-or-no responses.

Each EASE interview took 30-90 minutes.

The investigators found that patients with newly diagnosed schizophrenia spectrum disorder also had high levels of suicidality and self-disorders (P = .036) and high levels of depression (P less than .001). "Our main finding is that of a clear association between current suicidality and [self-disorders], which appears to be mediated by depression," Dr. Haug and her colleagues said (Compr. Psychiatry 2012;53:456-60).

This result "strongly support[s] the role of self-disorders in the development of suicidal ideation and behavior in this patient group."

In a previous study, other researchers postulated that patients with self-disorders experience specific feelings of inferiority and solitude, which differ from "normal" feelings of low self-esteem or loneliness and represent "more fundamental feelings of being profoundly dissimilar to other people and thus unable to relate to others," Dr. Haug and her associates noted.

If self-disorders play a key role in the development of depression in early schizophrenia, it follows that they "could be a rational clinical target for the prevention of suicidality," they added.

The investigators noted: "Our cross-sectional design makes it difficult to rule out the possibility that depressed patients develop and report more [self-disorders]. Previous studies of the temporal relationship between these factors, however, indicate that the subjective experience of psychologic deficits in patients with schizophrenia prone to depression is high even when they are not depressed."

This study was supported by Innlandet Hospital Trust, South-East Health Authority, Eastern Norway Health Authority, and a European Union Marie Curie Fellowship. No financial conflicts of interest were reported.

Among patients having their first episode of schizophrenia, suicidality is clearly associated with an altered sense of self, or what some experts have termed "self-disorders," a study of 49 adult patients shows.

Self-disorders are anomalous subjective experiences, described as "subtle disturbances of the person’s spontaneous experience of himself or herself as a vital subject naturally immersed in the world. As nonpsychotic distortions of self-awareness, they antedate the development of clearly delusional experiences and are highly prevalent in the prodromal and early psychotic phases" of schizophrenia, said Dr. Elisabeth Haug of the division of mental health, Innlandet Hospital Trust, Ottestad, Norway, and her associates.

The investigators assessed the relationship between self-disorders and suicidality in patients newly diagnosed as having schizophrenia spectrum disorder, because suicide risk is particularly high at this stage of the disease. They used data from the Norwegian Thematically Organized Psychosis study, which collected information from all mental health treatment facilities covering two counties with a pooled population of 375,000 people.

The study sample of 49 adults had been diagnosed over a 2-year period as having schizophrenia (38 patients), schizoaffective disorder (9 patients), or schizophreniform disorder (2 patients).

All the study subjects were assessed using the Examination of Anomalous Self Experience (EASE) manual, a 57-item questionnaire that addresses five domains of self-disorders: cognition and stream-of-consciousness, self-awareness and presence, bodily experiences, demarcation/transitivism, and existential reorientation. It includes questions such as "Have you ever felt as if thoughts in your head are not really belonging to you?" and solicits descriptions or examples from the patient rather than simple yes-or-no responses.

Each EASE interview took 30-90 minutes.

The investigators found that patients with newly diagnosed schizophrenia spectrum disorder also had high levels of suicidality and self-disorders (P = .036) and high levels of depression (P less than .001). "Our main finding is that of a clear association between current suicidality and [self-disorders], which appears to be mediated by depression," Dr. Haug and her colleagues said (Compr. Psychiatry 2012;53:456-60).

This result "strongly support[s] the role of self-disorders in the development of suicidal ideation and behavior in this patient group."

In a previous study, other researchers postulated that patients with self-disorders experience specific feelings of inferiority and solitude, which differ from "normal" feelings of low self-esteem or loneliness and represent "more fundamental feelings of being profoundly dissimilar to other people and thus unable to relate to others," Dr. Haug and her associates noted.

If self-disorders play a key role in the development of depression in early schizophrenia, it follows that they "could be a rational clinical target for the prevention of suicidality," they added.

The investigators noted: "Our cross-sectional design makes it difficult to rule out the possibility that depressed patients develop and report more [self-disorders]. Previous studies of the temporal relationship between these factors, however, indicate that the subjective experience of psychologic deficits in patients with schizophrenia prone to depression is high even when they are not depressed."

This study was supported by Innlandet Hospital Trust, South-East Health Authority, Eastern Norway Health Authority, and a European Union Marie Curie Fellowship. No financial conflicts of interest were reported.

Guidelines concerning the important elements of annual well-woman visits, such as when to perform pelvic exams in asymptomatic patients and when to begin formal breast exams, are now available from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

At the annual visit, ob.gyns. should counsel women about maintaining a healthy lifestyle and minimizing their health risks. A physical examination also is key and should include obtaining vital signs, determining body mass index, palpating the abdomen and the inguinal lymph nodes, and assessing overall health, according to ACOG Committee Opinion No. 534.

Pelvic examinations and breast examinations are important at these visits for many, but not for all, women, the Committee on Gynecologic Practice stated (Obstet. Gynecol. 2012;120:421-4).

For example, pelvic exams are recommended annually for all women aged 21 and older, and are "an appropriate component of a comprehensive evaluation" for all women who report symptoms that suggest problems of the genital tract, pelvis, urinary tract, or rectum. Some of these include menstrual disorders, vaginal discharge, infertility, or pelvic pain.

However, pelvic exams are not recommended for women younger than 21 unless indicated by the medical history. "External-only" exams are adequate to assess and discuss with the patient the normal external genital anatomy, issues of person hygiene, and any abnormalities of the vulva, introitus, or perineum that may require further assessment. An external-only exam also gives the ob.gyn. an opportunity to discuss with these young patients the range of normal female anatomy.

For women younger than 21, pelvic exams are not necessary for conducting sexually transmitted infection screening for gonorrhea or chlamydia because nucleic acid amplification testing can be done on urine samples or self-collected vaginal swab specimens.* This method is also adequate for diagnosing yeast infections, trichomoniasis, and bacterial vaginosis in these young women.

Speculum examination for cervical cancer should commence at age 21, "irrespective of sexual activity of the patient," according to the committee opinion.

For older and perimenopausal women, pelvic exams are recommended if there is abnormal uterine bleeding, a change in bowel or bladder function, a vaginal bulge, urinary or fecal incontinence, or vaginal dryness or discomfort. They may be indicated by a woman’s personal or family history, especially for gynecologic malignancies. But otherwise, pelvic exams may be unnecessary in older women.

"It would be reasonable to stop performing pelvic examinations when a woman’s age or other health issues reach a point where the woman would not choose to intervene on conditions detected during the routine examination, particularly if she is discontinuing her other routine health care maintenance assessments," according to the opinion. "Sound clinical judgment always must be the guiding factor in determining when a pelvic examination is needed."

There are no data concerning the age at which to begin clinical breast examinations in asymptomatic, low-risk women, but expert opinion suggests that it depends on the woman’s age and risk factors for breast cancer. The committee members recommend breast exams every 1-3 years for women aged 20-39 years and annually for women aged 40 and older.

Teaching women breast self-awareness is appropriate at any age. This includes educating them about the normal feel and appearance of their breasts, as well as inquiring into their medical history and family history for factors related to breast disease. For many women, it also includes encouraging breast self-examination.

ACOG has made the comprehensive recommendations for annual health assessments available here.

All ACOG committee members are required to follow the college’s guidelines for relationships with the health care industry, according to the ACOG website.

* clarification made 8/15/2012

Guidelines concerning the important elements of annual well-woman visits, such as when to perform pelvic exams in asymptomatic patients and when to begin formal breast exams, are now available from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

At the annual visit, ob.gyns. should counsel women about maintaining a healthy lifestyle and minimizing their health risks. A physical examination also is key and should include obtaining vital signs, determining body mass index, palpating the abdomen and the inguinal lymph nodes, and assessing overall health, according to ACOG Committee Opinion No. 534.

Pelvic examinations and breast examinations are important at these visits for many, but not for all, women, the Committee on Gynecologic Practice stated (Obstet. Gynecol. 2012;120:421-4).

For example, pelvic exams are recommended annually for all women aged 21 and older, and are "an appropriate component of a comprehensive evaluation" for all women who report symptoms that suggest problems of the genital tract, pelvis, urinary tract, or rectum. Some of these include menstrual disorders, vaginal discharge, infertility, or pelvic pain.

However, pelvic exams are not recommended for women younger than 21 unless indicated by the medical history. "External-only" exams are adequate to assess and discuss with the patient the normal external genital anatomy, issues of person hygiene, and any abnormalities of the vulva, introitus, or perineum that may require further assessment. An external-only exam also gives the ob.gyn. an opportunity to discuss with these young patients the range of normal female anatomy.

For women younger than 21, pelvic exams are not necessary for conducting sexually transmitted infection screening for gonorrhea or chlamydia because nucleic acid amplification testing can be done on urine samples or self-collected vaginal swab specimens.* This method is also adequate for diagnosing yeast infections, trichomoniasis, and bacterial vaginosis in these young women.

Speculum examination for cervical cancer should commence at age 21, "irrespective of sexual activity of the patient," according to the committee opinion.

For older and perimenopausal women, pelvic exams are recommended if there is abnormal uterine bleeding, a change in bowel or bladder function, a vaginal bulge, urinary or fecal incontinence, or vaginal dryness or discomfort. They may be indicated by a woman’s personal or family history, especially for gynecologic malignancies. But otherwise, pelvic exams may be unnecessary in older women.

"It would be reasonable to stop performing pelvic examinations when a woman’s age or other health issues reach a point where the woman would not choose to intervene on conditions detected during the routine examination, particularly if she is discontinuing her other routine health care maintenance assessments," according to the opinion. "Sound clinical judgment always must be the guiding factor in determining when a pelvic examination is needed."

There are no data concerning the age at which to begin clinical breast examinations in asymptomatic, low-risk women, but expert opinion suggests that it depends on the woman’s age and risk factors for breast cancer. The committee members recommend breast exams every 1-3 years for women aged 20-39 years and annually for women aged 40 and older.

Teaching women breast self-awareness is appropriate at any age. This includes educating them about the normal feel and appearance of their breasts, as well as inquiring into their medical history and family history for factors related to breast disease. For many women, it also includes encouraging breast self-examination.

ACOG has made the comprehensive recommendations for annual health assessments available here.

All ACOG committee members are required to follow the college’s guidelines for relationships with the health care industry, according to the ACOG website.

* clarification made 8/15/2012

Guidelines concerning the important elements of annual well-woman visits, such as when to perform pelvic exams in asymptomatic patients and when to begin formal breast exams, are now available from the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice.

At the annual visit, ob.gyns. should counsel women about maintaining a healthy lifestyle and minimizing their health risks. A physical examination also is key and should include obtaining vital signs, determining body mass index, palpating the abdomen and the inguinal lymph nodes, and assessing overall health, according to ACOG Committee Opinion No. 534.

Pelvic examinations and breast examinations are important at these visits for many, but not for all, women, the Committee on Gynecologic Practice stated (Obstet. Gynecol. 2012;120:421-4).

For example, pelvic exams are recommended annually for all women aged 21 and older, and are "an appropriate component of a comprehensive evaluation" for all women who report symptoms that suggest problems of the genital tract, pelvis, urinary tract, or rectum. Some of these include menstrual disorders, vaginal discharge, infertility, or pelvic pain.

However, pelvic exams are not recommended for women younger than 21 unless indicated by the medical history. "External-only" exams are adequate to assess and discuss with the patient the normal external genital anatomy, issues of person hygiene, and any abnormalities of the vulva, introitus, or perineum that may require further assessment. An external-only exam also gives the ob.gyn. an opportunity to discuss with these young patients the range of normal female anatomy.

For women younger than 21, pelvic exams are not necessary for conducting sexually transmitted infection screening for gonorrhea or chlamydia because nucleic acid amplification testing can be done on urine samples or self-collected vaginal swab specimens.* This method is also adequate for diagnosing yeast infections, trichomoniasis, and bacterial vaginosis in these young women.

Speculum examination for cervical cancer should commence at age 21, "irrespective of sexual activity of the patient," according to the committee opinion.

For older and perimenopausal women, pelvic exams are recommended if there is abnormal uterine bleeding, a change in bowel or bladder function, a vaginal bulge, urinary or fecal incontinence, or vaginal dryness or discomfort. They may be indicated by a woman’s personal or family history, especially for gynecologic malignancies. But otherwise, pelvic exams may be unnecessary in older women.

"It would be reasonable to stop performing pelvic examinations when a woman’s age or other health issues reach a point where the woman would not choose to intervene on conditions detected during the routine examination, particularly if she is discontinuing her other routine health care maintenance assessments," according to the opinion. "Sound clinical judgment always must be the guiding factor in determining when a pelvic examination is needed."

There are no data concerning the age at which to begin clinical breast examinations in asymptomatic, low-risk women, but expert opinion suggests that it depends on the woman’s age and risk factors for breast cancer. The committee members recommend breast exams every 1-3 years for women aged 20-39 years and annually for women aged 40 and older.

Teaching women breast self-awareness is appropriate at any age. This includes educating them about the normal feel and appearance of their breasts, as well as inquiring into their medical history and family history for factors related to breast disease. For many women, it also includes encouraging breast self-examination.

ACOG has made the comprehensive recommendations for annual health assessments available here.

All ACOG committee members are required to follow the college’s guidelines for relationships with the health care industry, according to the ACOG website.

* clarification made 8/15/2012

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Interferon-beta therapy did not slow the long-term progression of disability in adults with relapsing-remitting multiple sclerosis in a retrospective cohort study based on prospectively collected data.

Patients who took interferon-beta (IFN-beta) experienced rates of disease progression that were similar to a group of contemporaneous peers who did not take IFN-beta and a historical cohort of MS patients studied before IFN-beta therapy became available, Dr. Afsaneh Shirani of the Brain Research Centre at Vancouver (B.C.) Coastal Health Research Institute and her associates reported July 18 in JAMA.

These findings are consistent with those of the longer-term clinical trials that have examined IFN-beta’s efficacy in MS. They call into question the routine use of the drug to prevent or delay disability, the researchers noted.

Previous postmarketing studies have suggested that IFN-beta is beneficial in slowing the progression of MS, but many of those studies had methodologic flaws. For their study, Dr. Shirani and her colleagues used information from a province-wide database that is thought to cover 80% of the MS patients in British Columbia.

The investigators compared outcomes in 868 patients who took IFN-beta in 1995-2004 with 829 contemporaneous control patients who were eligible to take the drug during the same period but chose not to. They also assessed outcomes in a historical control group of 959 unexposed patients who were studied in 1985-1995 before IFN-beta was approved for use in Canada.

At baseline, the study subjects in all three groups had median scores of 2.0 on the 10-point Expanded Disability Status Scale (EDSS), in which higher scores indicate more-severe disability.

Most (76%) of the study subjects were women, and the mean age at onset of MS was 32 years. Median length of follow-up was 5 years for the group receiving IFN-beta, 4 years for their contemporaries who did not receive IFN-beta, and 11 years for the historical controls.

There was no evidence of an association between IFN-beta therapy and MS progression. A total of 94 patients in the treated group (11%), 44 (5%) in the contemporaneous control group, and 222 (23%) in the historical control group reached the main outcome of a sustained, irreversible EDSS score of 6. That score indicates "intermittent or unilateral constant assistance (cane, crutch, or brace) required to walk about 100 meters, with or without resting," according to the investigators, who said that the differences between the groups were not significant (JAMA 2012;308:247-56).

These results did not change appreciably when the data were adjusted to account for differences among the study groups in comorbidity and socioeconomic status, nor did they change in any of several sensitivity analyses.

The results were also similar for a secondary outcome measure, the attainment of an EDSS score of 4 (indicating "fully ambulatory without aid, up and about 12 hours a day despite relatively severe disability; able to walk without aid for 500 meters"). A total of 156 (18%) patients in the treated group, 68 (8%) in the contemporaneous control group, and 268 (28%) in the historical control group reached this end point. These differences also were not statistically significant.

The study is limited by the fact that factors other than IFN-beta treatment may have changed over time, which could bias the comparison with the historical control group. In addition, the decision to forgo IFN-beta therapy may have been related to several factors that could not be accounted for in this observational study, which could bias the comparison with the contemporaneous control group. For example, patients may have decided against IFN-beta therapy because they were in a stable phase of disease, had a needle phobia, were unable or unwilling to adhere to a noncurative treatment, wanted to become pregnant, or had personal or religious objections to using a drug that contains human albumin, Dr. Shirani and her associates said.

It is possible that a subgroup of relapsing-remitting MS patients may benefit from IFN-beta. "Further work is needed to identify these potential patients; perhaps through pharmacogenomic or biomarker studies, paving the way for a tailored, personalized medicine approach," they added.

This study was supported by the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Canada, the Michael Smith Foundation for Health Research, the Christopher Foundation, the University of British Columbia, the Medical Services Commission of British Columbia, the Natural Sciences and Engineering Research Council of Canada, and the United Kingdom Multiple Sclerosis Trust. Dr. Shirani’s associates reported numerous ties to industry sources.

Interferon-beta therapy did not slow the long-term progression of disability in adults with relapsing-remitting multiple sclerosis in a retrospective cohort study based on prospectively collected data.

Patients who took interferon-beta (IFN-beta) experienced rates of disease progression that were similar to a group of contemporaneous peers who did not take IFN-beta and a historical cohort of MS patients studied before IFN-beta therapy became available, Dr. Afsaneh Shirani of the Brain Research Centre at Vancouver (B.C.) Coastal Health Research Institute and her associates reported July 18 in JAMA.

These findings are consistent with those of the longer-term clinical trials that have examined IFN-beta’s efficacy in MS. They call into question the routine use of the drug to prevent or delay disability, the researchers noted.

Previous postmarketing studies have suggested that IFN-beta is beneficial in slowing the progression of MS, but many of those studies had methodologic flaws. For their study, Dr. Shirani and her colleagues used information from a province-wide database that is thought to cover 80% of the MS patients in British Columbia.

The investigators compared outcomes in 868 patients who took IFN-beta in 1995-2004 with 829 contemporaneous control patients who were eligible to take the drug during the same period but chose not to. They also assessed outcomes in a historical control group of 959 unexposed patients who were studied in 1985-1995 before IFN-beta was approved for use in Canada.

At baseline, the study subjects in all three groups had median scores of 2.0 on the 10-point Expanded Disability Status Scale (EDSS), in which higher scores indicate more-severe disability.

Most (76%) of the study subjects were women, and the mean age at onset of MS was 32 years. Median length of follow-up was 5 years for the group receiving IFN-beta, 4 years for their contemporaries who did not receive IFN-beta, and 11 years for the historical controls.

There was no evidence of an association between IFN-beta therapy and MS progression. A total of 94 patients in the treated group (11%), 44 (5%) in the contemporaneous control group, and 222 (23%) in the historical control group reached the main outcome of a sustained, irreversible EDSS score of 6. That score indicates "intermittent or unilateral constant assistance (cane, crutch, or brace) required to walk about 100 meters, with or without resting," according to the investigators, who said that the differences between the groups were not significant (JAMA 2012;308:247-56).

These results did not change appreciably when the data were adjusted to account for differences among the study groups in comorbidity and socioeconomic status, nor did they change in any of several sensitivity analyses.

The results were also similar for a secondary outcome measure, the attainment of an EDSS score of 4 (indicating "fully ambulatory without aid, up and about 12 hours a day despite relatively severe disability; able to walk without aid for 500 meters"). A total of 156 (18%) patients in the treated group, 68 (8%) in the contemporaneous control group, and 268 (28%) in the historical control group reached this end point. These differences also were not statistically significant.

The study is limited by the fact that factors other than IFN-beta treatment may have changed over time, which could bias the comparison with the historical control group. In addition, the decision to forgo IFN-beta therapy may have been related to several factors that could not be accounted for in this observational study, which could bias the comparison with the contemporaneous control group. For example, patients may have decided against IFN-beta therapy because they were in a stable phase of disease, had a needle phobia, were unable or unwilling to adhere to a noncurative treatment, wanted to become pregnant, or had personal or religious objections to using a drug that contains human albumin, Dr. Shirani and her associates said.

It is possible that a subgroup of relapsing-remitting MS patients may benefit from IFN-beta. "Further work is needed to identify these potential patients; perhaps through pharmacogenomic or biomarker studies, paving the way for a tailored, personalized medicine approach," they added.

This study was supported by the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Canada, the Michael Smith Foundation for Health Research, the Christopher Foundation, the University of British Columbia, the Medical Services Commission of British Columbia, the Natural Sciences and Engineering Research Council of Canada, and the United Kingdom Multiple Sclerosis Trust. Dr. Shirani’s associates reported numerous ties to industry sources.

Interferon-beta therapy did not slow the long-term progression of disability in adults with relapsing-remitting multiple sclerosis in a retrospective cohort study based on prospectively collected data.

Patients who took interferon-beta (IFN-beta) experienced rates of disease progression that were similar to a group of contemporaneous peers who did not take IFN-beta and a historical cohort of MS patients studied before IFN-beta therapy became available, Dr. Afsaneh Shirani of the Brain Research Centre at Vancouver (B.C.) Coastal Health Research Institute and her associates reported July 18 in JAMA.

These findings are consistent with those of the longer-term clinical trials that have examined IFN-beta’s efficacy in MS. They call into question the routine use of the drug to prevent or delay disability, the researchers noted.

Previous postmarketing studies have suggested that IFN-beta is beneficial in slowing the progression of MS, but many of those studies had methodologic flaws. For their study, Dr. Shirani and her colleagues used information from a province-wide database that is thought to cover 80% of the MS patients in British Columbia.

The investigators compared outcomes in 868 patients who took IFN-beta in 1995-2004 with 829 contemporaneous control patients who were eligible to take the drug during the same period but chose not to. They also assessed outcomes in a historical control group of 959 unexposed patients who were studied in 1985-1995 before IFN-beta was approved for use in Canada.

At baseline, the study subjects in all three groups had median scores of 2.0 on the 10-point Expanded Disability Status Scale (EDSS), in which higher scores indicate more-severe disability.

Most (76%) of the study subjects were women, and the mean age at onset of MS was 32 years. Median length of follow-up was 5 years for the group receiving IFN-beta, 4 years for their contemporaries who did not receive IFN-beta, and 11 years for the historical controls.

There was no evidence of an association between IFN-beta therapy and MS progression. A total of 94 patients in the treated group (11%), 44 (5%) in the contemporaneous control group, and 222 (23%) in the historical control group reached the main outcome of a sustained, irreversible EDSS score of 6. That score indicates "intermittent or unilateral constant assistance (cane, crutch, or brace) required to walk about 100 meters, with or without resting," according to the investigators, who said that the differences between the groups were not significant (JAMA 2012;308:247-56).

These results did not change appreciably when the data were adjusted to account for differences among the study groups in comorbidity and socioeconomic status, nor did they change in any of several sensitivity analyses.

The results were also similar for a secondary outcome measure, the attainment of an EDSS score of 4 (indicating "fully ambulatory without aid, up and about 12 hours a day despite relatively severe disability; able to walk without aid for 500 meters"). A total of 156 (18%) patients in the treated group, 68 (8%) in the contemporaneous control group, and 268 (28%) in the historical control group reached this end point. These differences also were not statistically significant.

The study is limited by the fact that factors other than IFN-beta treatment may have changed over time, which could bias the comparison with the historical control group. In addition, the decision to forgo IFN-beta therapy may have been related to several factors that could not be accounted for in this observational study, which could bias the comparison with the contemporaneous control group. For example, patients may have decided against IFN-beta therapy because they were in a stable phase of disease, had a needle phobia, were unable or unwilling to adhere to a noncurative treatment, wanted to become pregnant, or had personal or religious objections to using a drug that contains human albumin, Dr. Shirani and her associates said.

It is possible that a subgroup of relapsing-remitting MS patients may benefit from IFN-beta. "Further work is needed to identify these potential patients; perhaps through pharmacogenomic or biomarker studies, paving the way for a tailored, personalized medicine approach," they added.

This study was supported by the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Canada, the Michael Smith Foundation for Health Research, the Christopher Foundation, the University of British Columbia, the Medical Services Commission of British Columbia, the Natural Sciences and Engineering Research Council of Canada, and the United Kingdom Multiple Sclerosis Trust. Dr. Shirani’s associates reported numerous ties to industry sources.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

© forestpath - Fotolia.com

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

© forestpath - Fotolia.com

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

© forestpath - Fotolia.com

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.