Michele G. Sullivan

Prehospital administration of ticagrelor did not improve either short- or long-term outcomes for patients with ST-elevation myocardial infarction over the standard in-hospital administration of the drug.

Patients who received ticagrelor in the field had virtually identical rates of 70% or greater post–percutaneous coronary intervention resolution and post-PCI cardiovascular events as those who got the drug after hospital admission, Dr. Gilles Montalescot and his colleagues reported at the online at the annual congress of the European Society of Cardiology. The results were simultaneously published online (N. Engl. J. Med. 2014 Sept. 1; [doi:10.1056/NEJMoa1407024]).

The phase IV ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary artery) trial, conducted in 112 PCI centers among 13 countries, randomized 1,862 patients with ongoing STEMI of less than 6 hours’ duration to either a 180-mg loading dose of ticagrelor before hospital transfer, or to the same protocol in the PCI lab. All patients then received an ongoing regimen of 90 mg twice daily for 30 days, with the recommendation that this be continued for 12 months. Some patients also received glycoprotein IIB/IIIa inhibitors in the ambulance, but this was delivered at the physicians’ discretion.

In addition to STEMI resolution, primary endpoint included the proportion of patients who didn’t meet TIMI flow grade 3 in the infarcted artery before PCI. Secondary endpoints were a composite measure of death, MI, stent thrombosis, or urgent revascularization at 30 days; thrombotic bailout with glycoprotein inhibition, TIMI flow grade 3 at the end of the procedure, and complete STEMI resolution at by 60 minutes after PCI, reported Dr. Montalescot, director of cardiac care at the Pitié-Salpêtrière Hospital in Paris, and his coauthors.

Safety endpoints included major bleeding after PCI.

The patients were a mean of 61 years old. About 19% had a body mass index of 30 kg/m² or higher. For 75%, the first point of care was in the ambulance. About 30% had glycoprotein inhibition before PCI.

The rates of a STEMI resolution of at least 70% were almost identical in the prehospital and in-hospital groups (86.8% and 87.6%, respectively), as was the absence of TIMI flow grade 3 in the infarcted artery by the time of PCI (82.6% and 83.1%). Likewise, a similar proportion of patients met either one or both secondary endpoints (49.6% and 52.8%).

While there was no significant between-group difference in the composite endpoint, stent thrombosis at 24 hours after PCI was lower in the prehospital group than in the in-hospital group (0% and 8%, respectively), and also at 30 days afterward (0.2% and 1.2%).

In all, 49 patients died, 30 in the prehospital group and 19 in the in-hospital group – not a significant difference (3.3% vs. 2%). The most common causes were cardiogenic shock, cardiac arrest, mechanical complications, and heart failure.

Major bleeding rates within the first 48 hours were low and similar (1.8% vs.1.6%); 30-day rates were identical (1.2% vs. 1.2%).

"Our study shows that there is no downside to earlier administration of ticagrelor, and it reduces the risk of post-procedure stent thrombosis. ... It is also a more practical time point for administration of the drug than in the catheterisation laboratory, where considerable staff and technical demands already exist," Dr. Montalescot said in a statement.

AstraZeneca sponsored the study. Dr. Montalescot reported receiving grants from the company and other pharmaceutical companies. He also reported consulting fees from 25 different pharmaceutical companies and study groups, including the ATLANTIC study.

The coauthors also reported numerous financial relationships with pharmaceutical companies, including AstraZeneca.

[email protected]

On Twitter @alz_gal

Prehospital administration of ticagrelor did not improve either short- or long-term outcomes for patients with ST-elevation myocardial infarction over the standard in-hospital administration of the drug.

Patients who received ticagrelor in the field had virtually identical rates of 70% or greater post–percutaneous coronary intervention resolution and post-PCI cardiovascular events as those who got the drug after hospital admission, Dr. Gilles Montalescot and his colleagues reported at the online at the annual congress of the European Society of Cardiology. The results were simultaneously published online (N. Engl. J. Med. 2014 Sept. 1; [doi:10.1056/NEJMoa1407024]).

The phase IV ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary artery) trial, conducted in 112 PCI centers among 13 countries, randomized 1,862 patients with ongoing STEMI of less than 6 hours’ duration to either a 180-mg loading dose of ticagrelor before hospital transfer, or to the same protocol in the PCI lab. All patients then received an ongoing regimen of 90 mg twice daily for 30 days, with the recommendation that this be continued for 12 months. Some patients also received glycoprotein IIB/IIIa inhibitors in the ambulance, but this was delivered at the physicians’ discretion.

In addition to STEMI resolution, primary endpoint included the proportion of patients who didn’t meet TIMI flow grade 3 in the infarcted artery before PCI. Secondary endpoints were a composite measure of death, MI, stent thrombosis, or urgent revascularization at 30 days; thrombotic bailout with glycoprotein inhibition, TIMI flow grade 3 at the end of the procedure, and complete STEMI resolution at by 60 minutes after PCI, reported Dr. Montalescot, director of cardiac care at the Pitié-Salpêtrière Hospital in Paris, and his coauthors.

Safety endpoints included major bleeding after PCI.

The patients were a mean of 61 years old. About 19% had a body mass index of 30 kg/m² or higher. For 75%, the first point of care was in the ambulance. About 30% had glycoprotein inhibition before PCI.

The rates of a STEMI resolution of at least 70% were almost identical in the prehospital and in-hospital groups (86.8% and 87.6%, respectively), as was the absence of TIMI flow grade 3 in the infarcted artery by the time of PCI (82.6% and 83.1%). Likewise, a similar proportion of patients met either one or both secondary endpoints (49.6% and 52.8%).

While there was no significant between-group difference in the composite endpoint, stent thrombosis at 24 hours after PCI was lower in the prehospital group than in the in-hospital group (0% and 8%, respectively), and also at 30 days afterward (0.2% and 1.2%).

In all, 49 patients died, 30 in the prehospital group and 19 in the in-hospital group – not a significant difference (3.3% vs. 2%). The most common causes were cardiogenic shock, cardiac arrest, mechanical complications, and heart failure.

Major bleeding rates within the first 48 hours were low and similar (1.8% vs.1.6%); 30-day rates were identical (1.2% vs. 1.2%).

"Our study shows that there is no downside to earlier administration of ticagrelor, and it reduces the risk of post-procedure stent thrombosis. ... It is also a more practical time point for administration of the drug than in the catheterisation laboratory, where considerable staff and technical demands already exist," Dr. Montalescot said in a statement.

AstraZeneca sponsored the study. Dr. Montalescot reported receiving grants from the company and other pharmaceutical companies. He also reported consulting fees from 25 different pharmaceutical companies and study groups, including the ATLANTIC study.

The coauthors also reported numerous financial relationships with pharmaceutical companies, including AstraZeneca.

[email protected]

On Twitter @alz_gal

Prehospital administration of ticagrelor did not improve either short- or long-term outcomes for patients with ST-elevation myocardial infarction over the standard in-hospital administration of the drug.

Patients who received ticagrelor in the field had virtually identical rates of 70% or greater post–percutaneous coronary intervention resolution and post-PCI cardiovascular events as those who got the drug after hospital admission, Dr. Gilles Montalescot and his colleagues reported at the online at the annual congress of the European Society of Cardiology. The results were simultaneously published online (N. Engl. J. Med. 2014 Sept. 1; [doi:10.1056/NEJMoa1407024]).

The phase IV ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary artery) trial, conducted in 112 PCI centers among 13 countries, randomized 1,862 patients with ongoing STEMI of less than 6 hours’ duration to either a 180-mg loading dose of ticagrelor before hospital transfer, or to the same protocol in the PCI lab. All patients then received an ongoing regimen of 90 mg twice daily for 30 days, with the recommendation that this be continued for 12 months. Some patients also received glycoprotein IIB/IIIa inhibitors in the ambulance, but this was delivered at the physicians’ discretion.

In addition to STEMI resolution, primary endpoint included the proportion of patients who didn’t meet TIMI flow grade 3 in the infarcted artery before PCI. Secondary endpoints were a composite measure of death, MI, stent thrombosis, or urgent revascularization at 30 days; thrombotic bailout with glycoprotein inhibition, TIMI flow grade 3 at the end of the procedure, and complete STEMI resolution at by 60 minutes after PCI, reported Dr. Montalescot, director of cardiac care at the Pitié-Salpêtrière Hospital in Paris, and his coauthors.

Safety endpoints included major bleeding after PCI.

The patients were a mean of 61 years old. About 19% had a body mass index of 30 kg/m² or higher. For 75%, the first point of care was in the ambulance. About 30% had glycoprotein inhibition before PCI.

The rates of a STEMI resolution of at least 70% were almost identical in the prehospital and in-hospital groups (86.8% and 87.6%, respectively), as was the absence of TIMI flow grade 3 in the infarcted artery by the time of PCI (82.6% and 83.1%). Likewise, a similar proportion of patients met either one or both secondary endpoints (49.6% and 52.8%).

While there was no significant between-group difference in the composite endpoint, stent thrombosis at 24 hours after PCI was lower in the prehospital group than in the in-hospital group (0% and 8%, respectively), and also at 30 days afterward (0.2% and 1.2%).

In all, 49 patients died, 30 in the prehospital group and 19 in the in-hospital group – not a significant difference (3.3% vs. 2%). The most common causes were cardiogenic shock, cardiac arrest, mechanical complications, and heart failure.

Major bleeding rates within the first 48 hours were low and similar (1.8% vs.1.6%); 30-day rates were identical (1.2% vs. 1.2%).

"Our study shows that there is no downside to earlier administration of ticagrelor, and it reduces the risk of post-procedure stent thrombosis. ... It is also a more practical time point for administration of the drug than in the catheterisation laboratory, where considerable staff and technical demands already exist," Dr. Montalescot said in a statement.

AstraZeneca sponsored the study. Dr. Montalescot reported receiving grants from the company and other pharmaceutical companies. He also reported consulting fees from 25 different pharmaceutical companies and study groups, including the ATLANTIC study.

The coauthors also reported numerous financial relationships with pharmaceutical companies, including AstraZeneca.

[email protected]

On Twitter @alz_gal

A drug designed to stabilize atherosclerotic plaques failed to reduce the risk of major coronary events when given to patients hospitalized with an acute coronary syndrome.

After 2.5 years, there was no significant difference between darapladib and placebo in a composite endpoint of coronary heart disease, death, myocardial infarction, or urgent coronary revascularization (16.3% vs. 15.6%). Nor did the drug confer any significant benefit when each of these outcomes was separately examined, Dr. Michelle L. O’Donoghue and her colleagues reported at the annual congress of the European Society of Cardiology. The study was simultaneously published online in the Journal of the American Medical Association (JAMA 2014 [doi:10.1001/jama.2014.11061]).

Subgroup analyses of the SOLID-TIMI 52 study also failed to identify any patient group that experienced any significant benefit in the composite or individual endpoints, reported Dr. O’Donoghue of Brigham and Women’s Hospital, Boston, and her coauthors.

Darapladib is an investigational selective inhibitor of lipoprotein-associated phospholipase A₂ (Lp-PLA₂); it has been shown to prevent the expansion of necrotic cores in atherosclerotic plaques.

The study randomized 13,026 patients to either darapladib 160 mg/day or placebo. They were a median of 64 years old; 75% were male. The initial acute coronary events were ST-elevation myocardial infarction (45%), non-ST-elevation MI (43%), and unstable angina (12%). Cardiac catheterization was common (86%), as was percutaneous coronary intervention (77%)

Nearly all patients were taking statins at baseline (95%). More than 85% were also taking other recommended therapies, including aspirin, beta-blockers, and antiplatelet agents.

By the end of the follow-up period, the primary combined endpoint had occurred in 903 patients in the active group and 910 in the placebo group (HR 1.00). The secondary endpoint (cardiovascular death, MI, or stroke) occurred in 824 taking darapladib and 838 taking placebo (15% each; HR 0.99).

Death occurred in 7% of each group (HR 0.94).

The authors conducted several subgroup analyses and failed to find a significant benefit regardless of age, geographical region, renal dysfunction or any other baseline comorbidities. Baseline low-density lipoprotein cholesterol had no interaction with outcomes.

Darapladib was considered safe; the incidence of any serious adverse events was similar to placebo (45% vs. 46%). Alamine aminotransferase elevations occurred in less than 1% of each group.

Adverse events leading to discontinuation occurred in 17% of the active group and 12% of the placebo group. This significant difference was mostly driven by body odor events in the darapladib group.

"Consistent with prior studies, patients treated with darapladib were more likely to report an odor-related concern than those in the placebo group," at 11% vs. 2%, the authors noted.

These included skin odors (4% vs. 0.4%), urine odors (5% vs. 1%), and feces odors (8% vs. 1%). Diarrhea was also significantly more common among those taking the study drug (11% vs. 6%).

SOLID-TIMI 52 is the drug’s second failed phase III trial. The STABILITY study, which followed almost 16,000 patients for more than 3 years, also found that darapladib conferred no significant benefit in major cardiovascular outcomes.

These findings, combined with the current study, suggest that Lp-PLA₂ may not be a good therapeutic target for a population already sufficiently treated with plaque-stabilizing statins, Dr. O’Donoghue and her coauthors said. "In addition, although unlikely, the possibility that Lp-PLA remains an important target cannot be excluded, but variable plaque penetration of the drug or unidentified off-target effects of darapladib could be responsible for the absence of efficacy in the current study."

The SOLID-TIMI 52 trial was funded by GlaxoSmithKline. Dr. O’Donoghue has received institutional research funding from the company, and has consulting fees from Aegerion. Her coauthors disclosed relationships with numerous pharmaceutical companies.

[email protected]

A drug designed to stabilize atherosclerotic plaques failed to reduce the risk of major coronary events when given to patients hospitalized with an acute coronary syndrome.

After 2.5 years, there was no significant difference between darapladib and placebo in a composite endpoint of coronary heart disease, death, myocardial infarction, or urgent coronary revascularization (16.3% vs. 15.6%). Nor did the drug confer any significant benefit when each of these outcomes was separately examined, Dr. Michelle L. O’Donoghue and her colleagues reported at the annual congress of the European Society of Cardiology. The study was simultaneously published online in the Journal of the American Medical Association (JAMA 2014 [doi:10.1001/jama.2014.11061]).

Subgroup analyses of the SOLID-TIMI 52 study also failed to identify any patient group that experienced any significant benefit in the composite or individual endpoints, reported Dr. O’Donoghue of Brigham and Women’s Hospital, Boston, and her coauthors.

Darapladib is an investigational selective inhibitor of lipoprotein-associated phospholipase A₂ (Lp-PLA₂); it has been shown to prevent the expansion of necrotic cores in atherosclerotic plaques.

The study randomized 13,026 patients to either darapladib 160 mg/day or placebo. They were a median of 64 years old; 75% were male. The initial acute coronary events were ST-elevation myocardial infarction (45%), non-ST-elevation MI (43%), and unstable angina (12%). Cardiac catheterization was common (86%), as was percutaneous coronary intervention (77%)

Nearly all patients were taking statins at baseline (95%). More than 85% were also taking other recommended therapies, including aspirin, beta-blockers, and antiplatelet agents.

By the end of the follow-up period, the primary combined endpoint had occurred in 903 patients in the active group and 910 in the placebo group (HR 1.00). The secondary endpoint (cardiovascular death, MI, or stroke) occurred in 824 taking darapladib and 838 taking placebo (15% each; HR 0.99).

Death occurred in 7% of each group (HR 0.94).

The authors conducted several subgroup analyses and failed to find a significant benefit regardless of age, geographical region, renal dysfunction or any other baseline comorbidities. Baseline low-density lipoprotein cholesterol had no interaction with outcomes.

Darapladib was considered safe; the incidence of any serious adverse events was similar to placebo (45% vs. 46%). Alamine aminotransferase elevations occurred in less than 1% of each group.

Adverse events leading to discontinuation occurred in 17% of the active group and 12% of the placebo group. This significant difference was mostly driven by body odor events in the darapladib group.

"Consistent with prior studies, patients treated with darapladib were more likely to report an odor-related concern than those in the placebo group," at 11% vs. 2%, the authors noted.

These included skin odors (4% vs. 0.4%), urine odors (5% vs. 1%), and feces odors (8% vs. 1%). Diarrhea was also significantly more common among those taking the study drug (11% vs. 6%).

SOLID-TIMI 52 is the drug’s second failed phase III trial. The STABILITY study, which followed almost 16,000 patients for more than 3 years, also found that darapladib conferred no significant benefit in major cardiovascular outcomes.

These findings, combined with the current study, suggest that Lp-PLA₂ may not be a good therapeutic target for a population already sufficiently treated with plaque-stabilizing statins, Dr. O’Donoghue and her coauthors said. "In addition, although unlikely, the possibility that Lp-PLA remains an important target cannot be excluded, but variable plaque penetration of the drug or unidentified off-target effects of darapladib could be responsible for the absence of efficacy in the current study."

The SOLID-TIMI 52 trial was funded by GlaxoSmithKline. Dr. O’Donoghue has received institutional research funding from the company, and has consulting fees from Aegerion. Her coauthors disclosed relationships with numerous pharmaceutical companies.

[email protected]

A drug designed to stabilize atherosclerotic plaques failed to reduce the risk of major coronary events when given to patients hospitalized with an acute coronary syndrome.

After 2.5 years, there was no significant difference between darapladib and placebo in a composite endpoint of coronary heart disease, death, myocardial infarction, or urgent coronary revascularization (16.3% vs. 15.6%). Nor did the drug confer any significant benefit when each of these outcomes was separately examined, Dr. Michelle L. O’Donoghue and her colleagues reported at the annual congress of the European Society of Cardiology. The study was simultaneously published online in the Journal of the American Medical Association (JAMA 2014 [doi:10.1001/jama.2014.11061]).

Subgroup analyses of the SOLID-TIMI 52 study also failed to identify any patient group that experienced any significant benefit in the composite or individual endpoints, reported Dr. O’Donoghue of Brigham and Women’s Hospital, Boston, and her coauthors.

Darapladib is an investigational selective inhibitor of lipoprotein-associated phospholipase A₂ (Lp-PLA₂); it has been shown to prevent the expansion of necrotic cores in atherosclerotic plaques.

The study randomized 13,026 patients to either darapladib 160 mg/day or placebo. They were a median of 64 years old; 75% were male. The initial acute coronary events were ST-elevation myocardial infarction (45%), non-ST-elevation MI (43%), and unstable angina (12%). Cardiac catheterization was common (86%), as was percutaneous coronary intervention (77%)

Nearly all patients were taking statins at baseline (95%). More than 85% were also taking other recommended therapies, including aspirin, beta-blockers, and antiplatelet agents.

By the end of the follow-up period, the primary combined endpoint had occurred in 903 patients in the active group and 910 in the placebo group (HR 1.00). The secondary endpoint (cardiovascular death, MI, or stroke) occurred in 824 taking darapladib and 838 taking placebo (15% each; HR 0.99).

Death occurred in 7% of each group (HR 0.94).

The authors conducted several subgroup analyses and failed to find a significant benefit regardless of age, geographical region, renal dysfunction or any other baseline comorbidities. Baseline low-density lipoprotein cholesterol had no interaction with outcomes.

Darapladib was considered safe; the incidence of any serious adverse events was similar to placebo (45% vs. 46%). Alamine aminotransferase elevations occurred in less than 1% of each group.

Adverse events leading to discontinuation occurred in 17% of the active group and 12% of the placebo group. This significant difference was mostly driven by body odor events in the darapladib group.

"Consistent with prior studies, patients treated with darapladib were more likely to report an odor-related concern than those in the placebo group," at 11% vs. 2%, the authors noted.

These included skin odors (4% vs. 0.4%), urine odors (5% vs. 1%), and feces odors (8% vs. 1%). Diarrhea was also significantly more common among those taking the study drug (11% vs. 6%).

SOLID-TIMI 52 is the drug’s second failed phase III trial. The STABILITY study, which followed almost 16,000 patients for more than 3 years, also found that darapladib conferred no significant benefit in major cardiovascular outcomes.

These findings, combined with the current study, suggest that Lp-PLA₂ may not be a good therapeutic target for a population already sufficiently treated with plaque-stabilizing statins, Dr. O’Donoghue and her coauthors said. "In addition, although unlikely, the possibility that Lp-PLA remains an important target cannot be excluded, but variable plaque penetration of the drug or unidentified off-target effects of darapladib could be responsible for the absence of efficacy in the current study."

The SOLID-TIMI 52 trial was funded by GlaxoSmithKline. Dr. O’Donoghue has received institutional research funding from the company, and has consulting fees from Aegerion. Her coauthors disclosed relationships with numerous pharmaceutical companies.

[email protected]

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

Coronary artery disease may develop at a younger age in patients with inflammatory bowel disease, even when they have fewer traditional risk factors for heart problems.

A database review of patients with CAD has determined that those with IBD were significantly younger, less heavy, and less likely to smoke than matched controls, Dr. Ashish Aggarwal and his colleagues reported in the August issue of Inflammatory Bowel Diseases (Inflamm. Bowel Dis. 2014;20:1593-601).

"These findings support the theory that traditional risk factors may not be sufficient to predict the risk of coronary artery disease in patients with IBD, and that inflammation may play a key role in the pathogenesis of atherosclerosis," wrote Dr. Aggarwal of the Cleveland Clinic and his coauthors.

The team reviewed both CAD risk factors and the outcomes of percutaneous interventions in a group of 655 patients with CAD: 131 of these had an IBD, including 54 with Crohn’s and 77 with ulcerative colitis.

The most common phenotypes among those with Crohn’s were ileocolonic disease location (39%) and nonstricturing, nonpenetrating disease (48%). Among patients with ulcerative colitis, half had extensive or pancolitis. About two-thirds of those with IBD had taken steroids at some point.

Patients with IBD were significantly younger than the control patients (65 vs. 68 years). They were also less likely to be smokers (11% vs. 19%), and had a lower mean body mass index (28 vs. 29.4 kg/m²).

However, there were no significant between-group differences in hypertension, diabetes, or hyperlipidemia. Platelet counts were similar, as were C-reactive protein levels.

The mean Framingham risk scores were 7.3 for those with IBD and 7.7 for those without – not a significant difference.

Despite their similarities in Framingham risk, the IBD patients were significantly less likely to have severe left anterior descending (LAD) disease (56% vs. 73%). They were also less likely – though not significantly so – to have multivessel disease (71% vs. 79%) and had fewer involved vessels (two vs. three).

Percutaneous coronary intervention was necessary for 28% of those with IBD and 35% of those without. Again, IBD patients were younger, had lower BMI, and were less often smokers.

The overall PCI success rate was similar, but patients with IBD were half as likely to have a major cardiac adverse event (13% vs. 24%) or die during follow-up (6.5% vs. 13.4%) – although again, these differences did not reach significance (P = .28).

Two patients with IBD and 16 without needed a repeat revascularization. IBD exercised no significant increase in the risk of any post-PCI major cardiovascular outcome.

The authors suggested that anti-inflammatory drugs based on salicylic acid compounds may offer IBD patients some cardioprotection – an idea supported by a large Danish cohort study (PLoS One 2013;8:e56944). It concluded that CAD incidence was significantly lower among those who took salicylic-based medications (relative risks, 1.16 vs. 1.36).

"Furthermore, patients with IBD were less likely to be active smokers or obese as found in our study, which again could lower the risk for future cardiovascular events," they added.

The authors had no financial disclosures; the study sponsor was not indicated.

[email protected]

Coronary artery disease may develop at a younger age in patients with inflammatory bowel disease, even when they have fewer traditional risk factors for heart problems.

A database review of patients with CAD has determined that those with IBD were significantly younger, less heavy, and less likely to smoke than matched controls, Dr. Ashish Aggarwal and his colleagues reported in the August issue of Inflammatory Bowel Diseases (Inflamm. Bowel Dis. 2014;20:1593-601).

"These findings support the theory that traditional risk factors may not be sufficient to predict the risk of coronary artery disease in patients with IBD, and that inflammation may play a key role in the pathogenesis of atherosclerosis," wrote Dr. Aggarwal of the Cleveland Clinic and his coauthors.

The team reviewed both CAD risk factors and the outcomes of percutaneous interventions in a group of 655 patients with CAD: 131 of these had an IBD, including 54 with Crohn’s and 77 with ulcerative colitis.

The most common phenotypes among those with Crohn’s were ileocolonic disease location (39%) and nonstricturing, nonpenetrating disease (48%). Among patients with ulcerative colitis, half had extensive or pancolitis. About two-thirds of those with IBD had taken steroids at some point.

Patients with IBD were significantly younger than the control patients (65 vs. 68 years). They were also less likely to be smokers (11% vs. 19%), and had a lower mean body mass index (28 vs. 29.4 kg/m²).

However, there were no significant between-group differences in hypertension, diabetes, or hyperlipidemia. Platelet counts were similar, as were C-reactive protein levels.

The mean Framingham risk scores were 7.3 for those with IBD and 7.7 for those without – not a significant difference.

Despite their similarities in Framingham risk, the IBD patients were significantly less likely to have severe left anterior descending (LAD) disease (56% vs. 73%). They were also less likely – though not significantly so – to have multivessel disease (71% vs. 79%) and had fewer involved vessels (two vs. three).

Percutaneous coronary intervention was necessary for 28% of those with IBD and 35% of those without. Again, IBD patients were younger, had lower BMI, and were less often smokers.

The overall PCI success rate was similar, but patients with IBD were half as likely to have a major cardiac adverse event (13% vs. 24%) or die during follow-up (6.5% vs. 13.4%) – although again, these differences did not reach significance (P = .28).

Two patients with IBD and 16 without needed a repeat revascularization. IBD exercised no significant increase in the risk of any post-PCI major cardiovascular outcome.

The authors suggested that anti-inflammatory drugs based on salicylic acid compounds may offer IBD patients some cardioprotection – an idea supported by a large Danish cohort study (PLoS One 2013;8:e56944). It concluded that CAD incidence was significantly lower among those who took salicylic-based medications (relative risks, 1.16 vs. 1.36).

"Furthermore, patients with IBD were less likely to be active smokers or obese as found in our study, which again could lower the risk for future cardiovascular events," they added.

The authors had no financial disclosures; the study sponsor was not indicated.

[email protected]

Coronary artery disease may develop at a younger age in patients with inflammatory bowel disease, even when they have fewer traditional risk factors for heart problems.

A database review of patients with CAD has determined that those with IBD were significantly younger, less heavy, and less likely to smoke than matched controls, Dr. Ashish Aggarwal and his colleagues reported in the August issue of Inflammatory Bowel Diseases (Inflamm. Bowel Dis. 2014;20:1593-601).

"These findings support the theory that traditional risk factors may not be sufficient to predict the risk of coronary artery disease in patients with IBD, and that inflammation may play a key role in the pathogenesis of atherosclerosis," wrote Dr. Aggarwal of the Cleveland Clinic and his coauthors.

The team reviewed both CAD risk factors and the outcomes of percutaneous interventions in a group of 655 patients with CAD: 131 of these had an IBD, including 54 with Crohn’s and 77 with ulcerative colitis.

The most common phenotypes among those with Crohn’s were ileocolonic disease location (39%) and nonstricturing, nonpenetrating disease (48%). Among patients with ulcerative colitis, half had extensive or pancolitis. About two-thirds of those with IBD had taken steroids at some point.

Patients with IBD were significantly younger than the control patients (65 vs. 68 years). They were also less likely to be smokers (11% vs. 19%), and had a lower mean body mass index (28 vs. 29.4 kg/m²).

However, there were no significant between-group differences in hypertension, diabetes, or hyperlipidemia. Platelet counts were similar, as were C-reactive protein levels.

The mean Framingham risk scores were 7.3 for those with IBD and 7.7 for those without – not a significant difference.

Despite their similarities in Framingham risk, the IBD patients were significantly less likely to have severe left anterior descending (LAD) disease (56% vs. 73%). They were also less likely – though not significantly so – to have multivessel disease (71% vs. 79%) and had fewer involved vessels (two vs. three).

Percutaneous coronary intervention was necessary for 28% of those with IBD and 35% of those without. Again, IBD patients were younger, had lower BMI, and were less often smokers.

The overall PCI success rate was similar, but patients with IBD were half as likely to have a major cardiac adverse event (13% vs. 24%) or die during follow-up (6.5% vs. 13.4%) – although again, these differences did not reach significance (P = .28).

Two patients with IBD and 16 without needed a repeat revascularization. IBD exercised no significant increase in the risk of any post-PCI major cardiovascular outcome.

The authors suggested that anti-inflammatory drugs based on salicylic acid compounds may offer IBD patients some cardioprotection – an idea supported by a large Danish cohort study (PLoS One 2013;8:e56944). It concluded that CAD incidence was significantly lower among those who took salicylic-based medications (relative risks, 1.16 vs. 1.36).

"Furthermore, patients with IBD were less likely to be active smokers or obese as found in our study, which again could lower the risk for future cardiovascular events," they added.

The authors had no financial disclosures; the study sponsor was not indicated.

[email protected]

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]

Compared with medication alone, the combination of optimized medical treatment and cognitive therapy affected a high rate of recovery for patients with severe, nonchronic major depressive disorder.

Although the combination didn’t significantly benefit patients with less severe or chronic depression, it doubled recovery rates among those with the most severe symptoms. The number needed to treat to achieve one recovery in this group was just three, Steven D. Hollon, Ph.D., and his colleagues reported Aug. 20 in the journal (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2014.1054]).

The failure to observe a significant benefit among those less severely and chronically depressed patients disappointed, wrote Dr. Hollon, who is the Gertrude Conaway Professor of Psychology at Vanderbilt University, Nashville, Tenn.

But this dichotomy could be employed as a way to pinpoint those most likely to respond to the combination.

"[These moderators] could be used prescriptively to guide a more efficient allocation of treatment resources. Given the higher cost of combined treatment, it might be reserved for patients with nonchronic, more severe depression. Such a recommendation would be consistent with the goals of personalized medicine; patients are given what they most need and costly resources are reserved for those likely to benefit from them."

The 42-month trial randomized 452 patients with chronic or recurrent major depressive disorder to optimized antidepressant treatment or antidepressants plus cognitive therapy. They were a mean of 43 years old with a mean score of 22 on the Hamilton Rating Scale for Depression (HRSD). Recurrent depression was present in 83%; chronic, in 35%. The overall dropout rate was 23%, but attrition was significantly lower in the combination group (19% vs. 27%).

Overall, the rates of remission did not significantly differ between the groups. However, recovery was significantly more common among those who had the combination therapy (73% vs. 63%; hazard ratio, 1.33), with a number needed to treat of 10.

An exploratory analysis determined that the timing of depression and its severity significantly influenced outcomes. Among those with either less severe depression or high-severity chronic depression, the treatment effect was small. But among those with severe, nonchronic depression, a significant benefit was found. The recovery rate for these patients was significantly higher with combination therapy (81% vs. 52%; HR, 2.34), with a number needed to treat of three.

Patients in the combination treatment group also experienced significantly fewer serious adverse events, probably because they spent less time in major depressive episodes, the authors suggested.

Dr. Hollon reported no financial disclosures. However, his coauthors reported relationships with multiple pharmaceutical companies. The National Institutes of Mental Health funded the study. Wyeth Pharmaceuticals and Pfizer provided some study medications.

[email protected]

On Twitter @alz_gal

Compared with medication alone, the combination of optimized medical treatment and cognitive therapy affected a high rate of recovery for patients with severe, nonchronic major depressive disorder.

Although the combination didn’t significantly benefit patients with less severe or chronic depression, it doubled recovery rates among those with the most severe symptoms. The number needed to treat to achieve one recovery in this group was just three, Steven D. Hollon, Ph.D., and his colleagues reported Aug. 20 in the journal (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2014.1054]).

The failure to observe a significant benefit among those less severely and chronically depressed patients disappointed, wrote Dr. Hollon, who is the Gertrude Conaway Professor of Psychology at Vanderbilt University, Nashville, Tenn.

But this dichotomy could be employed as a way to pinpoint those most likely to respond to the combination.

"[These moderators] could be used prescriptively to guide a more efficient allocation of treatment resources. Given the higher cost of combined treatment, it might be reserved for patients with nonchronic, more severe depression. Such a recommendation would be consistent with the goals of personalized medicine; patients are given what they most need and costly resources are reserved for those likely to benefit from them."

The 42-month trial randomized 452 patients with chronic or recurrent major depressive disorder to optimized antidepressant treatment or antidepressants plus cognitive therapy. They were a mean of 43 years old with a mean score of 22 on the Hamilton Rating Scale for Depression (HRSD). Recurrent depression was present in 83%; chronic, in 35%. The overall dropout rate was 23%, but attrition was significantly lower in the combination group (19% vs. 27%).

Overall, the rates of remission did not significantly differ between the groups. However, recovery was significantly more common among those who had the combination therapy (73% vs. 63%; hazard ratio, 1.33), with a number needed to treat of 10.

An exploratory analysis determined that the timing of depression and its severity significantly influenced outcomes. Among those with either less severe depression or high-severity chronic depression, the treatment effect was small. But among those with severe, nonchronic depression, a significant benefit was found. The recovery rate for these patients was significantly higher with combination therapy (81% vs. 52%; HR, 2.34), with a number needed to treat of three.

Patients in the combination treatment group also experienced significantly fewer serious adverse events, probably because they spent less time in major depressive episodes, the authors suggested.

Dr. Hollon reported no financial disclosures. However, his coauthors reported relationships with multiple pharmaceutical companies. The National Institutes of Mental Health funded the study. Wyeth Pharmaceuticals and Pfizer provided some study medications.

[email protected]

On Twitter @alz_gal

Compared with medication alone, the combination of optimized medical treatment and cognitive therapy affected a high rate of recovery for patients with severe, nonchronic major depressive disorder.

Although the combination didn’t significantly benefit patients with less severe or chronic depression, it doubled recovery rates among those with the most severe symptoms. The number needed to treat to achieve one recovery in this group was just three, Steven D. Hollon, Ph.D., and his colleagues reported Aug. 20 in the journal (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2014.1054]).

The failure to observe a significant benefit among those less severely and chronically depressed patients disappointed, wrote Dr. Hollon, who is the Gertrude Conaway Professor of Psychology at Vanderbilt University, Nashville, Tenn.

But this dichotomy could be employed as a way to pinpoint those most likely to respond to the combination.

"[These moderators] could be used prescriptively to guide a more efficient allocation of treatment resources. Given the higher cost of combined treatment, it might be reserved for patients with nonchronic, more severe depression. Such a recommendation would be consistent with the goals of personalized medicine; patients are given what they most need and costly resources are reserved for those likely to benefit from them."

The 42-month trial randomized 452 patients with chronic or recurrent major depressive disorder to optimized antidepressant treatment or antidepressants plus cognitive therapy. They were a mean of 43 years old with a mean score of 22 on the Hamilton Rating Scale for Depression (HRSD). Recurrent depression was present in 83%; chronic, in 35%. The overall dropout rate was 23%, but attrition was significantly lower in the combination group (19% vs. 27%).

Overall, the rates of remission did not significantly differ between the groups. However, recovery was significantly more common among those who had the combination therapy (73% vs. 63%; hazard ratio, 1.33), with a number needed to treat of 10.

An exploratory analysis determined that the timing of depression and its severity significantly influenced outcomes. Among those with either less severe depression or high-severity chronic depression, the treatment effect was small. But among those with severe, nonchronic depression, a significant benefit was found. The recovery rate for these patients was significantly higher with combination therapy (81% vs. 52%; HR, 2.34), with a number needed to treat of three.

Patients in the combination treatment group also experienced significantly fewer serious adverse events, probably because they spent less time in major depressive episodes, the authors suggested.

Dr. Hollon reported no financial disclosures. However, his coauthors reported relationships with multiple pharmaceutical companies. The National Institutes of Mental Health funded the study. Wyeth Pharmaceuticals and Pfizer provided some study medications.

[email protected]

On Twitter @alz_gal

Brief drug-abuse interventions typically used in primary care and emergency departments simply don’t work, two randomized trials have concluded.

Neither of the approaches in the trials decreased illicit drug use over a 6-12 month follow-up period. The findings don’t support the use of the programs, Dr. Richard Saitz and Dr. Peter P. Roy-Byrne reported in the Aug. 5 issue of JAMA.

While such interventions might be helpful for smoking and alcohol use, they are probably too simplistic for the multifactorial problem of drug use, which involves not only personal choice, but medical, psychological, social, and, possibly, legal issues, wrote Dr. Saitz of the department of community health sciences at Boston University, and his colleagues (JAMA 2014;312:502-13).

"Despite the potential for benefit with this approach, drug use differs from unhealthy alcohol use in that it is often illegal and socially unacceptable, and is diverse – from occasional marijuana use, which was illegal during this study, to numerous daily heroin injections," the investigators noted. "Prescription drug misuse is particularly complex, with diagnostic confusion between misuse for symptoms (pain, anxiety), euphoria-seeking, and drug diversion. Brief counseling may simply be inadequate to address these complexities, even as an initial strategy."

Dr. Saitz’s study took place in a hospital-based urban primary care practice. After identifying patients with high scores on the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), the researchers randomized 528 patients to one of three arms: a brief negotiated interview (BNI), an adaptation of motivational interviewing (MOTIV), or a control group of no intervention.

The BNI was a 10- to 15-minute structured interview conducted by health educators. The MOTIV was a 30- to 45-minute intervention based on motivational interviewing, with a 20- to 30-minute booster conducted by master’s degree–level counselors. The booster session was conducted by telephone 6 weeks after the initial interaction. All study participants received a written list of substance use disorder treatment and mutual help resources. The final assessment was conducted at 6 months

Most of the patients (70%) were men; the mean age was 41 years. Marijuana was the most commonly used substance (63%), followed by cocaine (19%) and opioids (17%) and prescription opioids (6%). The mean baseline ASSIST score was at least 27 in 18% of the cohort. During the prior month, patients had used drugs a mean of 14 days.

Follow-up was very good, with 98% of patients available for assessment. Compared with the control group, however, neither intervention group showed any benefit from intervention.

At 6 months, the mean ASSIST score was at least 27 in 20% of the MOTIV and 19% of the control group but had risen to 25% in the BNI group. The mean number of drug use days per month was 14 for all three groups. When the analysis was stratified by particular drug, the results were unchanged.

Motivational interviewing fell flat

The second study was conducted in seven primary care safety-net settings in King County, Washington (JAMA 2014;312:492-501). The investigators randomized 868 patients to enhanced care as usual, which included a list of drug abuse resources; or motivational interviewing, plus the resource handout and a 10-minute telephone booster at 2 weeks. All patients were assessed at 3, 6, 9, and 12 months.

Most of the patients were men (70%), with a mean age of 48 years. Most were unemployed (91%). A total of 30% reported being homeless at least 1 night in the prior 3 months. Medical comorbidities were common, with 26% reporting recent hospitalizations and half a recent emergency department visit. A total of 11% had received prior treatment for substance abuse. The mean number of drug use days in the past month was 14. The mean composite Addiction Severity Index (ASI) was 0.11.

"The treatment [outcomes were] virtually identical," with minimal change in either intervention over the 12-month follow-up period, wrote Dr. Roy-Byrne of the department of psychiatry and behavioral sciences at the University of Washington, Seattle, and his coauthors. "There is no evidence of an intervention effect."

Mean days used of the most commonly used drug at 3 months were 12 for the brief intervention and 10 for enhanced care – not significantly different from each other or from baseline. The mean ASI composite score at 3 months was 0.10 in the brief intervention group and 0.09 in the enhanced care group, neither of which was significantly different from baseline.

There were also no differences in the secondary outcomes of medical and psychiatric comorbidity; employment, social, and legal domains; or the number of patients who accepted a referral to chemical dependency treatment.

Refer, then follow up

Both studies’ findings are not surprising, Dr. Peter D. Friedmann said in an interview.

"Drugs are much more reinforcing than alcohol or tobacco, and so are their effects on behavior," said Dr. Friedmann, an internist at the Providence (R.I.) Veterans Affairs Medical Center. "This makes it much more difficult to extinguish drug use and its associated behaviors; that needs much more than just a brief counseling intervention."

Patients struggling with substance abuse need – and deserve – more than such a brief addressing of their problem, said Dr. Friedmann, also professor of health services, policy, and practice at Brown University, also in Providence. Medical treatment is a good first step and feasible for a primary care physician to administer in the office. Unfortunately, such treatment is only available for opiate misuse.

Extensive counseling, however, is beyond the purview of these doctors, he said, so expert referral with follow-up is a must.

"But we can’t simply refer and say, ‘Come back to me in 2 or 3 months, and we’ll see where you are.’ If we refer someone to a cardiologist, we follow up, we make sure the patient got there, and we expect a note back from the cardiologist," Dr. Friedmann said. "That doesn’t happen with drug referrals."

Dr. Friedmann acknowledged that there is scant literature supporting this kind of primary care. But that doesn’t mean it’s not helpful, or that it shouldn’t be done, he said.

"We do a lot of things in medicine for which there is no randomized, controlled evidence of effect. We do it because it’s our professional duty," he explained. "If we are confronted with someone who is struggling with this problem, even if it’s hard to find the evidence, it is part of our obligation to help."

The National Institute on Drug Abuse sponsored Dr. Roy-Byrne’s study. He had no financial disclosures, although several of his coauthors reported relationships with pharmaceutical companies. NIDA also supported Dr. Saitz’s study; he had no relevant disclosures.

Dr. Friedmann disclosed that he has received research support (medication only) from Alkermes and has been a speaker for Orexo.

[email protected]

On Twitter @alz_gal

Brief drug-abuse interventions typically used in primary care and emergency departments simply don’t work, two randomized trials have concluded.

Neither of the approaches in the trials decreased illicit drug use over a 6-12 month follow-up period. The findings don’t support the use of the programs, Dr. Richard Saitz and Dr. Peter P. Roy-Byrne reported in the Aug. 5 issue of JAMA.

While such interventions might be helpful for smoking and alcohol use, they are probably too simplistic for the multifactorial problem of drug use, which involves not only personal choice, but medical, psychological, social, and, possibly, legal issues, wrote Dr. Saitz of the department of community health sciences at Boston University, and his colleagues (JAMA 2014;312:502-13).

"Despite the potential for benefit with this approach, drug use differs from unhealthy alcohol use in that it is often illegal and socially unacceptable, and is diverse – from occasional marijuana use, which was illegal during this study, to numerous daily heroin injections," the investigators noted. "Prescription drug misuse is particularly complex, with diagnostic confusion between misuse for symptoms (pain, anxiety), euphoria-seeking, and drug diversion. Brief counseling may simply be inadequate to address these complexities, even as an initial strategy."

Dr. Saitz’s study took place in a hospital-based urban primary care practice. After identifying patients with high scores on the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), the researchers randomized 528 patients to one of three arms: a brief negotiated interview (BNI), an adaptation of motivational interviewing (MOTIV), or a control group of no intervention.

The BNI was a 10- to 15-minute structured interview conducted by health educators. The MOTIV was a 30- to 45-minute intervention based on motivational interviewing, with a 20- to 30-minute booster conducted by master’s degree–level counselors. The booster session was conducted by telephone 6 weeks after the initial interaction. All study participants received a written list of substance use disorder treatment and mutual help resources. The final assessment was conducted at 6 months

Most of the patients (70%) were men; the mean age was 41 years. Marijuana was the most commonly used substance (63%), followed by cocaine (19%) and opioids (17%) and prescription opioids (6%). The mean baseline ASSIST score was at least 27 in 18% of the cohort. During the prior month, patients had used drugs a mean of 14 days.

Follow-up was very good, with 98% of patients available for assessment. Compared with the control group, however, neither intervention group showed any benefit from intervention.

At 6 months, the mean ASSIST score was at least 27 in 20% of the MOTIV and 19% of the control group but had risen to 25% in the BNI group. The mean number of drug use days per month was 14 for all three groups. When the analysis was stratified by particular drug, the results were unchanged.

Motivational interviewing fell flat

The second study was conducted in seven primary care safety-net settings in King County, Washington (JAMA 2014;312:492-501). The investigators randomized 868 patients to enhanced care as usual, which included a list of drug abuse resources; or motivational interviewing, plus the resource handout and a 10-minute telephone booster at 2 weeks. All patients were assessed at 3, 6, 9, and 12 months.

Most of the patients were men (70%), with a mean age of 48 years. Most were unemployed (91%). A total of 30% reported being homeless at least 1 night in the prior 3 months. Medical comorbidities were common, with 26% reporting recent hospitalizations and half a recent emergency department visit. A total of 11% had received prior treatment for substance abuse. The mean number of drug use days in the past month was 14. The mean composite Addiction Severity Index (ASI) was 0.11.

"The treatment [outcomes were] virtually identical," with minimal change in either intervention over the 12-month follow-up period, wrote Dr. Roy-Byrne of the department of psychiatry and behavioral sciences at the University of Washington, Seattle, and his coauthors. "There is no evidence of an intervention effect."

Mean days used of the most commonly used drug at 3 months were 12 for the brief intervention and 10 for enhanced care – not significantly different from each other or from baseline. The mean ASI composite score at 3 months was 0.10 in the brief intervention group and 0.09 in the enhanced care group, neither of which was significantly different from baseline.

There were also no differences in the secondary outcomes of medical and psychiatric comorbidity; employment, social, and legal domains; or the number of patients who accepted a referral to chemical dependency treatment.

Refer, then follow up

Both studies’ findings are not surprising, Dr. Peter D. Friedmann said in an interview.

"Drugs are much more reinforcing than alcohol or tobacco, and so are their effects on behavior," said Dr. Friedmann, an internist at the Providence (R.I.) Veterans Affairs Medical Center. "This makes it much more difficult to extinguish drug use and its associated behaviors; that needs much more than just a brief counseling intervention."

Patients struggling with substance abuse need – and deserve – more than such a brief addressing of their problem, said Dr. Friedmann, also professor of health services, policy, and practice at Brown University, also in Providence. Medical treatment is a good first step and feasible for a primary care physician to administer in the office. Unfortunately, such treatment is only available for opiate misuse.

Extensive counseling, however, is beyond the purview of these doctors, he said, so expert referral with follow-up is a must.

"But we can’t simply refer and say, ‘Come back to me in 2 or 3 months, and we’ll see where you are.’ If we refer someone to a cardiologist, we follow up, we make sure the patient got there, and we expect a note back from the cardiologist," Dr. Friedmann said. "That doesn’t happen with drug referrals."

Dr. Friedmann acknowledged that there is scant literature supporting this kind of primary care. But that doesn’t mean it’s not helpful, or that it shouldn’t be done, he said.

"We do a lot of things in medicine for which there is no randomized, controlled evidence of effect. We do it because it’s our professional duty," he explained. "If we are confronted with someone who is struggling with this problem, even if it’s hard to find the evidence, it is part of our obligation to help."

The National Institute on Drug Abuse sponsored Dr. Roy-Byrne’s study. He had no financial disclosures, although several of his coauthors reported relationships with pharmaceutical companies. NIDA also supported Dr. Saitz’s study; he had no relevant disclosures.

Dr. Friedmann disclosed that he has received research support (medication only) from Alkermes and has been a speaker for Orexo.

[email protected]

On Twitter @alz_gal

Brief drug-abuse interventions typically used in primary care and emergency departments simply don’t work, two randomized trials have concluded.

Neither of the approaches in the trials decreased illicit drug use over a 6-12 month follow-up period. The findings don’t support the use of the programs, Dr. Richard Saitz and Dr. Peter P. Roy-Byrne reported in the Aug. 5 issue of JAMA.

While such interventions might be helpful for smoking and alcohol use, they are probably too simplistic for the multifactorial problem of drug use, which involves not only personal choice, but medical, psychological, social, and, possibly, legal issues, wrote Dr. Saitz of the department of community health sciences at Boston University, and his colleagues (JAMA 2014;312:502-13).

"Despite the potential for benefit with this approach, drug use differs from unhealthy alcohol use in that it is often illegal and socially unacceptable, and is diverse – from occasional marijuana use, which was illegal during this study, to numerous daily heroin injections," the investigators noted. "Prescription drug misuse is particularly complex, with diagnostic confusion between misuse for symptoms (pain, anxiety), euphoria-seeking, and drug diversion. Brief counseling may simply be inadequate to address these complexities, even as an initial strategy."

Dr. Saitz’s study took place in a hospital-based urban primary care practice. After identifying patients with high scores on the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), the researchers randomized 528 patients to one of three arms: a brief negotiated interview (BNI), an adaptation of motivational interviewing (MOTIV), or a control group of no intervention.

The BNI was a 10- to 15-minute structured interview conducted by health educators. The MOTIV was a 30- to 45-minute intervention based on motivational interviewing, with a 20- to 30-minute booster conducted by master’s degree–level counselors. The booster session was conducted by telephone 6 weeks after the initial interaction. All study participants received a written list of substance use disorder treatment and mutual help resources. The final assessment was conducted at 6 months

Most of the patients (70%) were men; the mean age was 41 years. Marijuana was the most commonly used substance (63%), followed by cocaine (19%) and opioids (17%) and prescription opioids (6%). The mean baseline ASSIST score was at least 27 in 18% of the cohort. During the prior month, patients had used drugs a mean of 14 days.

Follow-up was very good, with 98% of patients available for assessment. Compared with the control group, however, neither intervention group showed any benefit from intervention.

At 6 months, the mean ASSIST score was at least 27 in 20% of the MOTIV and 19% of the control group but had risen to 25% in the BNI group. The mean number of drug use days per month was 14 for all three groups. When the analysis was stratified by particular drug, the results were unchanged.

Motivational interviewing fell flat

The second study was conducted in seven primary care safety-net settings in King County, Washington (JAMA 2014;312:492-501). The investigators randomized 868 patients to enhanced care as usual, which included a list of drug abuse resources; or motivational interviewing, plus the resource handout and a 10-minute telephone booster at 2 weeks. All patients were assessed at 3, 6, 9, and 12 months.

Most of the patients were men (70%), with a mean age of 48 years. Most were unemployed (91%). A total of 30% reported being homeless at least 1 night in the prior 3 months. Medical comorbidities were common, with 26% reporting recent hospitalizations and half a recent emergency department visit. A total of 11% had received prior treatment for substance abuse. The mean number of drug use days in the past month was 14. The mean composite Addiction Severity Index (ASI) was 0.11.

"The treatment [outcomes were] virtually identical," with minimal change in either intervention over the 12-month follow-up period, wrote Dr. Roy-Byrne of the department of psychiatry and behavioral sciences at the University of Washington, Seattle, and his coauthors. "There is no evidence of an intervention effect."

Mean days used of the most commonly used drug at 3 months were 12 for the brief intervention and 10 for enhanced care – not significantly different from each other or from baseline. The mean ASI composite score at 3 months was 0.10 in the brief intervention group and 0.09 in the enhanced care group, neither of which was significantly different from baseline.

There were also no differences in the secondary outcomes of medical and psychiatric comorbidity; employment, social, and legal domains; or the number of patients who accepted a referral to chemical dependency treatment.

Refer, then follow up

Both studies’ findings are not surprising, Dr. Peter D. Friedmann said in an interview.

"Drugs are much more reinforcing than alcohol or tobacco, and so are their effects on behavior," said Dr. Friedmann, an internist at the Providence (R.I.) Veterans Affairs Medical Center. "This makes it much more difficult to extinguish drug use and its associated behaviors; that needs much more than just a brief counseling intervention."

Patients struggling with substance abuse need – and deserve – more than such a brief addressing of their problem, said Dr. Friedmann, also professor of health services, policy, and practice at Brown University, also in Providence. Medical treatment is a good first step and feasible for a primary care physician to administer in the office. Unfortunately, such treatment is only available for opiate misuse.

Extensive counseling, however, is beyond the purview of these doctors, he said, so expert referral with follow-up is a must.

"But we can’t simply refer and say, ‘Come back to me in 2 or 3 months, and we’ll see where you are.’ If we refer someone to a cardiologist, we follow up, we make sure the patient got there, and we expect a note back from the cardiologist," Dr. Friedmann said. "That doesn’t happen with drug referrals."

Dr. Friedmann acknowledged that there is scant literature supporting this kind of primary care. But that doesn’t mean it’s not helpful, or that it shouldn’t be done, he said.

"We do a lot of things in medicine for which there is no randomized, controlled evidence of effect. We do it because it’s our professional duty," he explained. "If we are confronted with someone who is struggling with this problem, even if it’s hard to find the evidence, it is part of our obligation to help."

The National Institute on Drug Abuse sponsored Dr. Roy-Byrne’s study. He had no financial disclosures, although several of his coauthors reported relationships with pharmaceutical companies. NIDA also supported Dr. Saitz’s study; he had no relevant disclosures.

Dr. Friedmann disclosed that he has received research support (medication only) from Alkermes and has been a speaker for Orexo.

[email protected]

On Twitter @alz_gal

As cardiovascular risks increase, so does the protection offered by antihypertensive medications, a large meta-analysis has determined.

The review of 52,000 patients has also found that the number needed to treat decreased as risk levels increased. For those at lowest risk, treatment would prevent 14 cardiovascular events over 5 years; for those at highest risk, treatment would prevent 38 events/1,000 patients.

"This finding provides support for the notion that blood pressure–lowering treatment should target those at greatest cardiovascular risk, not just those with the highest blood pressure levels," Dr. Johan Sundström and his colleagues in the Blood Pressure Lowering Treatment Trialists’ Collaboration reported in the Aug. 16 issue of the Lancet. "A risk-based approach is likely to be more cost effective than a blood pressure-based approach and could simultaneously reduce the numbers of patients needing treatment, and control drug costs while increasing the numbers of averted strokes and heart attacks."

Dr. Sundström of Uppsala University, Sweden, and his team analyzed 11 studies that comprised 26 groups randomized to placebo or various antihypertensive medications. These included ACE inhibitor–based treatment; calcium channel blocker–based treatment; diuretic-based treatment; and more-intensive vs. less-intensive blood pressure–lowering regimens.

The final analysis included full 5-year data on about 52,000 patients. These were separated into four increasing risk groups, which the authors created based on age, sex, body mass index, systolic and diastolic blood pressures, other antihypertensive treatment, current smoking, diabetes, and history of cardiovascular disease. Interaction analyses for age and sex, age and smoking, age and diabetes, age and history of cardiovascular disease, and age and other antihypertensive treatment were also included. However, lipid measurements were not.

Those 5-year risk groups were less than 11%; 11%-15%; 15%-21%; and more than 21%.

The primary outcome was a composite of total major cardiovascular events (nonfatal stroke; death from cerebrovascular disease; coronary heart disease, including myocardial infarction; heart failure; and cardiovascular morbidity.) Secondary outcomes were stroke, coronary heart disease, heart failure, cardiovascular mortality, and total mortality.

Over the 5-year follow-up period, there were 4,167 cardiovascular events (8%). The number of events varied from low- to high-risk groups: 4.1% in the low-risk group, followed by 8.3%, 12.6%, and 18.6%.

"However," the investigators said, "in absolute terms, treating 1,000 patients in each group with blood pressure–lowering treatment for 5 years would prevent 14, 20, 24, and 38 cardiovascular events, respectively," a significant preventive effect (Lancet 2014 Aug. 16;384:591-8).

Inversely, the number needed to treat for 5 years to avoid 1 cardiovascular event decreased with increasing baseline risk, from 71 in the lowest-risk group, to 51 and 41 in the second and third risk groups, and down to 26 in the highest-risk group.

The drugs continued to exert a significant effect despite several subanalyses that controlled for a variety of factors. Indeed, when they examined the relationship between cardiovascular events and the magnitude of both systolic and diastolic blood pressure reduction, the authors found even greater absolute event reduction.

For example, in the highest-risk group when systolic blood pressure of at least 140 mm Hg declined by 16 points, 69 events would be prevented over 5 years. When diastolic pressure of at least 90 mm Hg declined in that group by 8 points, 76 events would be prevented.

Even a 4 mm Hg reduction in systolic and diastolic pressures in the high-risk would reduce events by 19 and 22, respectively.

Despite the findings of prior studies also showing the benefit of risk managing blood pressure, the technique has fallen out of favor, the authors noted. "In part at least, this reluctance to use absolute risk as a basis for decision making might be a result of the absence of direct evidence of effectiveness, which this study should go some way toward addressing."

As members of the Blood Pressure Lowering Treatment Trialists’ Collaboration, the authors received individual funding for their work. Dr. Sundström declared that he is on the advisory board for Itrim. A number of the other authors declared financial relationships with pharmaceutical companies.

[email protected]

On Twitter @alz_gal

As cardiovascular risks increase, so does the protection offered by antihypertensive medications, a large meta-analysis has determined.

The review of 52,000 patients has also found that the number needed to treat decreased as risk levels increased. For those at lowest risk, treatment would prevent 14 cardiovascular events over 5 years; for those at highest risk, treatment would prevent 38 events/1,000 patients.

"This finding provides support for the notion that blood pressure–lowering treatment should target those at greatest cardiovascular risk, not just those with the highest blood pressure levels," Dr. Johan Sundström and his colleagues in the Blood Pressure Lowering Treatment Trialists’ Collaboration reported in the Aug. 16 issue of the Lancet. "A risk-based approach is likely to be more cost effective than a blood pressure-based approach and could simultaneously reduce the numbers of patients needing treatment, and control drug costs while increasing the numbers of averted strokes and heart attacks."

Dr. Sundström of Uppsala University, Sweden, and his team analyzed 11 studies that comprised 26 groups randomized to placebo or various antihypertensive medications. These included ACE inhibitor–based treatment; calcium channel blocker–based treatment; diuretic-based treatment; and more-intensive vs. less-intensive blood pressure–lowering regimens.

The final analysis included full 5-year data on about 52,000 patients. These were separated into four increasing risk groups, which the authors created based on age, sex, body mass index, systolic and diastolic blood pressures, other antihypertensive treatment, current smoking, diabetes, and history of cardiovascular disease. Interaction analyses for age and sex, age and smoking, age and diabetes, age and history of cardiovascular disease, and age and other antihypertensive treatment were also included. However, lipid measurements were not.

Those 5-year risk groups were less than 11%; 11%-15%; 15%-21%; and more than 21%.

The primary outcome was a composite of total major cardiovascular events (nonfatal stroke; death from cerebrovascular disease; coronary heart disease, including myocardial infarction; heart failure; and cardiovascular morbidity.) Secondary outcomes were stroke, coronary heart disease, heart failure, cardiovascular mortality, and total mortality.

Over the 5-year follow-up period, there were 4,167 cardiovascular events (8%). The number of events varied from low- to high-risk groups: 4.1% in the low-risk group, followed by 8.3%, 12.6%, and 18.6%.

"However," the investigators said, "in absolute terms, treating 1,000 patients in each group with blood pressure–lowering treatment for 5 years would prevent 14, 20, 24, and 38 cardiovascular events, respectively," a significant preventive effect (Lancet 2014 Aug. 16;384:591-8).

Inversely, the number needed to treat for 5 years to avoid 1 cardiovascular event decreased with increasing baseline risk, from 71 in the lowest-risk group, to 51 and 41 in the second and third risk groups, and down to 26 in the highest-risk group.

The drugs continued to exert a significant effect despite several subanalyses that controlled for a variety of factors. Indeed, when they examined the relationship between cardiovascular events and the magnitude of both systolic and diastolic blood pressure reduction, the authors found even greater absolute event reduction.

For example, in the highest-risk group when systolic blood pressure of at least 140 mm Hg declined by 16 points, 69 events would be prevented over 5 years. When diastolic pressure of at least 90 mm Hg declined in that group by 8 points, 76 events would be prevented.

Even a 4 mm Hg reduction in systolic and diastolic pressures in the high-risk would reduce events by 19 and 22, respectively.

Despite the findings of prior studies also showing the benefit of risk managing blood pressure, the technique has fallen out of favor, the authors noted. "In part at least, this reluctance to use absolute risk as a basis for decision making might be a result of the absence of direct evidence of effectiveness, which this study should go some way toward addressing."

As members of the Blood Pressure Lowering Treatment Trialists’ Collaboration, the authors received individual funding for their work. Dr. Sundström declared that he is on the advisory board for Itrim. A number of the other authors declared financial relationships with pharmaceutical companies.

[email protected]

On Twitter @alz_gal

As cardiovascular risks increase, so does the protection offered by antihypertensive medications, a large meta-analysis has determined.

The review of 52,000 patients has also found that the number needed to treat decreased as risk levels increased. For those at lowest risk, treatment would prevent 14 cardiovascular events over 5 years; for those at highest risk, treatment would prevent 38 events/1,000 patients.

"This finding provides support for the notion that blood pressure–lowering treatment should target those at greatest cardiovascular risk, not just those with the highest blood pressure levels," Dr. Johan Sundström and his colleagues in the Blood Pressure Lowering Treatment Trialists’ Collaboration reported in the Aug. 16 issue of the Lancet. "A risk-based approach is likely to be more cost effective than a blood pressure-based approach and could simultaneously reduce the numbers of patients needing treatment, and control drug costs while increasing the numbers of averted strokes and heart attacks."

Dr. Sundström of Uppsala University, Sweden, and his team analyzed 11 studies that comprised 26 groups randomized to placebo or various antihypertensive medications. These included ACE inhibitor–based treatment; calcium channel blocker–based treatment; diuretic-based treatment; and more-intensive vs. less-intensive blood pressure–lowering regimens.

The final analysis included full 5-year data on about 52,000 patients. These were separated into four increasing risk groups, which the authors created based on age, sex, body mass index, systolic and diastolic blood pressures, other antihypertensive treatment, current smoking, diabetes, and history of cardiovascular disease. Interaction analyses for age and sex, age and smoking, age and diabetes, age and history of cardiovascular disease, and age and other antihypertensive treatment were also included. However, lipid measurements were not.

Those 5-year risk groups were less than 11%; 11%-15%; 15%-21%; and more than 21%.

The primary outcome was a composite of total major cardiovascular events (nonfatal stroke; death from cerebrovascular disease; coronary heart disease, including myocardial infarction; heart failure; and cardiovascular morbidity.) Secondary outcomes were stroke, coronary heart disease, heart failure, cardiovascular mortality, and total mortality.

Over the 5-year follow-up period, there were 4,167 cardiovascular events (8%). The number of events varied from low- to high-risk groups: 4.1% in the low-risk group, followed by 8.3%, 12.6%, and 18.6%.

"However," the investigators said, "in absolute terms, treating 1,000 patients in each group with blood pressure–lowering treatment for 5 years would prevent 14, 20, 24, and 38 cardiovascular events, respectively," a significant preventive effect (Lancet 2014 Aug. 16;384:591-8).

Inversely, the number needed to treat for 5 years to avoid 1 cardiovascular event decreased with increasing baseline risk, from 71 in the lowest-risk group, to 51 and 41 in the second and third risk groups, and down to 26 in the highest-risk group.

The drugs continued to exert a significant effect despite several subanalyses that controlled for a variety of factors. Indeed, when they examined the relationship between cardiovascular events and the magnitude of both systolic and diastolic blood pressure reduction, the authors found even greater absolute event reduction.

For example, in the highest-risk group when systolic blood pressure of at least 140 mm Hg declined by 16 points, 69 events would be prevented over 5 years. When diastolic pressure of at least 90 mm Hg declined in that group by 8 points, 76 events would be prevented.

Even a 4 mm Hg reduction in systolic and diastolic pressures in the high-risk would reduce events by 19 and 22, respectively.

Despite the findings of prior studies also showing the benefit of risk managing blood pressure, the technique has fallen out of favor, the authors noted. "In part at least, this reluctance to use absolute risk as a basis for decision making might be a result of the absence of direct evidence of effectiveness, which this study should go some way toward addressing."

As members of the Blood Pressure Lowering Treatment Trialists’ Collaboration, the authors received individual funding for their work. Dr. Sundström declared that he is on the advisory board for Itrim. A number of the other authors declared financial relationships with pharmaceutical companies.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Detection of tau neurofibrillary tangles in the brain via PET imaging highly correlates with memory decline and could serve as an accurate way to identify individuals at high risk of Alzheimer’s disease and track disease progression, according to the results of a prospective study.

In a group of cognitively normal elderly subjects, PET imaging with an investigational tau-specific radioligand showed a significant association between increased tau binding and progressive memory decline over 3 years. A second study found that increased binding effectively discriminated cognitively normal subjects from those with mild cognitive impairment (MCI) and Alzheimer’s dementia.

The studies hold great promise for the future of Alzheimer’s drug development, Dr. Keith Johnson said at the Alzheimer’s Association International Conference 2014.

"At this early stage of tau PET imaging, we do think we are able to visualize the second of the two cardinal pathologic processes," said Dr. Johnson, codirector of the Neuroimaging Program of the Massachusetts Alzheimer’s Disease Research Center at Harvard University, Cambridge, Mass. "Our initial findings indicate that the spread of tau to widespread cortical regions, in the presence of amyloid plaques, may be the smoking gun – the sign that indicates cognitive impairment is either imminent or underway."

The compound, [¹⁸F]T807, is being developed by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly.

The first study by Dr. Johnson and his colleagues looked at [¹⁸F]T807 binding in a group of 56 cognitively normal subjects with a mean age of 72 years. All were members of the Harvard Aging Brain Study. The ongoing project tracks amyloid-beta deposition with PET imaging, as well as other Alzheimer’s biomarkers, in a group of cognitively normal, healthy subjects. Each participant also undergoes an annual test of cognition.

Dr. Johnson’s investigation examined the relationship between tau binding and memory performance as assessed retrospectively with the six-trial Selective Reminding Test over a median 3-year period. The linear regression model controlled for amyloid-beta plaque burden, age, and education.

Over the study period, the investigators found a highly significant relationship between memory performance and [¹⁸F]T807 binding in the entorhinal cortex (P less than .008) and the inferior temporal cortex (P less than .006). Amyloid-beta binding was significantly associated with tau binding in both regions.

When the model included tau and amyloid-beta plaque burden, the relationship between memory performance and inferior temporal tau burden remained significant in the inferior temporal region, whereas memory performance was no longer associated with tau binding in the entorhinal cortex. The amyloid burden was a significant, independent predictor of memory decline in both models.

The second study demonstrated the ligand’s ability to discriminate between normal and impaired memory. This study cohort comprised 51 individuals (mean age, 74 years); 40 were cognitively normal, 6 had MCI, and 5 had Alzheimer’s disease. They also underwent both tau and amyloid-beta PET imaging.

Among the cognitively normal subjects, [¹⁸F]T807 uptake was concentrated in the hippocampus. It varied considerably in the temporal allocortex, and occurred at low levels in the neocortex.

Compared with the cognitively normal subjects, the MCI and Alzheimer’s patients showed significantly greater binding in the neocortical regions, particularly in the temporal and occipital lobes. Binding extended into the parietal and frontal regions in patients with advanced symptoms.

Among all subjects, those with greater entorhinal binding performed significantly worse on a measure of delayed recall. Worse memory performance was also associated with higher amyloid-beta binding.

"We saw a progressive increase in cortical tau going from the normal subjects to those with Alzheimer’s dementia, and this pattern was different from amyloid," Dr. Johnson said. "The amyloid plaques were more diffuse and appeared at an earlier stage than the tau tangles. Our hypothesis is that the tau appears closer to the action, indicating incident cognitive impairment. It shows that these are the people who have or are about to have cognitive impairment, while the amyloid scan shows a much earlier stage of the pathology."

Although these studies are preliminary, they show that tau imaging may benefit research as much as amyloid imaging has, Dr. Johnson said.

"Ten years ago, amyloid plaque detection changed much of what we do in Alzheimer’s research, enabling us to identify the pathology years before any symptoms develop. It’s had a huge impact on drug development, allowing us to focus in on the right people for research cohorts. Unfortunately, amyloid has only been half of the story."

This new ability to see tau neurofibrillary tangles in vivo "should eventually enable us to more efficiently develop preventive therapies and even treatments for the actual symptoms," he said.

Dr. Johnson has been an adviser or consultant for Siemens Healthcare Diagnostics, Genzyme, and Piramal Healthcare. He has received research funding from Avid Radiopharmaceuticals, Eli Lilly, and other companies.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Detection of tau neurofibrillary tangles in the brain via PET imaging highly correlates with memory decline and could serve as an accurate way to identify individuals at high risk of Alzheimer’s disease and track disease progression, according to the results of a prospective study.

In a group of cognitively normal elderly subjects, PET imaging with an investigational tau-specific radioligand showed a significant association between increased tau binding and progressive memory decline over 3 years. A second study found that increased binding effectively discriminated cognitively normal subjects from those with mild cognitive impairment (MCI) and Alzheimer’s dementia.

The studies hold great promise for the future of Alzheimer’s drug development, Dr. Keith Johnson said at the Alzheimer’s Association International Conference 2014.

"At this early stage of tau PET imaging, we do think we are able to visualize the second of the two cardinal pathologic processes," said Dr. Johnson, codirector of the Neuroimaging Program of the Massachusetts Alzheimer’s Disease Research Center at Harvard University, Cambridge, Mass. "Our initial findings indicate that the spread of tau to widespread cortical regions, in the presence of amyloid plaques, may be the smoking gun – the sign that indicates cognitive impairment is either imminent or underway."

The compound, [¹⁸F]T807, is being developed by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly.

The first study by Dr. Johnson and his colleagues looked at [¹⁸F]T807 binding in a group of 56 cognitively normal subjects with a mean age of 72 years. All were members of the Harvard Aging Brain Study. The ongoing project tracks amyloid-beta deposition with PET imaging, as well as other Alzheimer’s biomarkers, in a group of cognitively normal, healthy subjects. Each participant also undergoes an annual test of cognition.

Dr. Johnson’s investigation examined the relationship between tau binding and memory performance as assessed retrospectively with the six-trial Selective Reminding Test over a median 3-year period. The linear regression model controlled for amyloid-beta plaque burden, age, and education.

Over the study period, the investigators found a highly significant relationship between memory performance and [¹⁸F]T807 binding in the entorhinal cortex (P less than .008) and the inferior temporal cortex (P less than .006). Amyloid-beta binding was significantly associated with tau binding in both regions.

When the model included tau and amyloid-beta plaque burden, the relationship between memory performance and inferior temporal tau burden remained significant in the inferior temporal region, whereas memory performance was no longer associated with tau binding in the entorhinal cortex. The amyloid burden was a significant, independent predictor of memory decline in both models.

The second study demonstrated the ligand’s ability to discriminate between normal and impaired memory. This study cohort comprised 51 individuals (mean age, 74 years); 40 were cognitively normal, 6 had MCI, and 5 had Alzheimer’s disease. They also underwent both tau and amyloid-beta PET imaging.

Among the cognitively normal subjects, [¹⁸F]T807 uptake was concentrated in the hippocampus. It varied considerably in the temporal allocortex, and occurred at low levels in the neocortex.

Compared with the cognitively normal subjects, the MCI and Alzheimer’s patients showed significantly greater binding in the neocortical regions, particularly in the temporal and occipital lobes. Binding extended into the parietal and frontal regions in patients with advanced symptoms.

Among all subjects, those with greater entorhinal binding performed significantly worse on a measure of delayed recall. Worse memory performance was also associated with higher amyloid-beta binding.

"We saw a progressive increase in cortical tau going from the normal subjects to those with Alzheimer’s dementia, and this pattern was different from amyloid," Dr. Johnson said. "The amyloid plaques were more diffuse and appeared at an earlier stage than the tau tangles. Our hypothesis is that the tau appears closer to the action, indicating incident cognitive impairment. It shows that these are the people who have or are about to have cognitive impairment, while the amyloid scan shows a much earlier stage of the pathology."

Although these studies are preliminary, they show that tau imaging may benefit research as much as amyloid imaging has, Dr. Johnson said.

"Ten years ago, amyloid plaque detection changed much of what we do in Alzheimer’s research, enabling us to identify the pathology years before any symptoms develop. It’s had a huge impact on drug development, allowing us to focus in on the right people for research cohorts. Unfortunately, amyloid has only been half of the story."

This new ability to see tau neurofibrillary tangles in vivo "should eventually enable us to more efficiently develop preventive therapies and even treatments for the actual symptoms," he said.

Dr. Johnson has been an adviser or consultant for Siemens Healthcare Diagnostics, Genzyme, and Piramal Healthcare. He has received research funding from Avid Radiopharmaceuticals, Eli Lilly, and other companies.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Detection of tau neurofibrillary tangles in the brain via PET imaging highly correlates with memory decline and could serve as an accurate way to identify individuals at high risk of Alzheimer’s disease and track disease progression, according to the results of a prospective study.

In a group of cognitively normal elderly subjects, PET imaging with an investigational tau-specific radioligand showed a significant association between increased tau binding and progressive memory decline over 3 years. A second study found that increased binding effectively discriminated cognitively normal subjects from those with mild cognitive impairment (MCI) and Alzheimer’s dementia.

The studies hold great promise for the future of Alzheimer’s drug development, Dr. Keith Johnson said at the Alzheimer’s Association International Conference 2014.

"At this early stage of tau PET imaging, we do think we are able to visualize the second of the two cardinal pathologic processes," said Dr. Johnson, codirector of the Neuroimaging Program of the Massachusetts Alzheimer’s Disease Research Center at Harvard University, Cambridge, Mass. "Our initial findings indicate that the spread of tau to widespread cortical regions, in the presence of amyloid plaques, may be the smoking gun – the sign that indicates cognitive impairment is either imminent or underway."

The compound, [¹⁸F]T807, is being developed by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly.

The first study by Dr. Johnson and his colleagues looked at [¹⁸F]T807 binding in a group of 56 cognitively normal subjects with a mean age of 72 years. All were members of the Harvard Aging Brain Study. The ongoing project tracks amyloid-beta deposition with PET imaging, as well as other Alzheimer’s biomarkers, in a group of cognitively normal, healthy subjects. Each participant also undergoes an annual test of cognition.

Dr. Johnson’s investigation examined the relationship between tau binding and memory performance as assessed retrospectively with the six-trial Selective Reminding Test over a median 3-year period. The linear regression model controlled for amyloid-beta plaque burden, age, and education.

Over the study period, the investigators found a highly significant relationship between memory performance and [¹⁸F]T807 binding in the entorhinal cortex (P less than .008) and the inferior temporal cortex (P less than .006). Amyloid-beta binding was significantly associated with tau binding in both regions.

When the model included tau and amyloid-beta plaque burden, the relationship between memory performance and inferior temporal tau burden remained significant in the inferior temporal region, whereas memory performance was no longer associated with tau binding in the entorhinal cortex. The amyloid burden was a significant, independent predictor of memory decline in both models.

The second study demonstrated the ligand’s ability to discriminate between normal and impaired memory. This study cohort comprised 51 individuals (mean age, 74 years); 40 were cognitively normal, 6 had MCI, and 5 had Alzheimer’s disease. They also underwent both tau and amyloid-beta PET imaging.

Among the cognitively normal subjects, [¹⁸F]T807 uptake was concentrated in the hippocampus. It varied considerably in the temporal allocortex, and occurred at low levels in the neocortex.

Compared with the cognitively normal subjects, the MCI and Alzheimer’s patients showed significantly greater binding in the neocortical regions, particularly in the temporal and occipital lobes. Binding extended into the parietal and frontal regions in patients with advanced symptoms.

Among all subjects, those with greater entorhinal binding performed significantly worse on a measure of delayed recall. Worse memory performance was also associated with higher amyloid-beta binding.

"We saw a progressive increase in cortical tau going from the normal subjects to those with Alzheimer’s dementia, and this pattern was different from amyloid," Dr. Johnson said. "The amyloid plaques were more diffuse and appeared at an earlier stage than the tau tangles. Our hypothesis is that the tau appears closer to the action, indicating incident cognitive impairment. It shows that these are the people who have or are about to have cognitive impairment, while the amyloid scan shows a much earlier stage of the pathology."

Although these studies are preliminary, they show that tau imaging may benefit research as much as amyloid imaging has, Dr. Johnson said.

"Ten years ago, amyloid plaque detection changed much of what we do in Alzheimer’s research, enabling us to identify the pathology years before any symptoms develop. It’s had a huge impact on drug development, allowing us to focus in on the right people for research cohorts. Unfortunately, amyloid has only been half of the story."

This new ability to see tau neurofibrillary tangles in vivo "should eventually enable us to more efficiently develop preventive therapies and even treatments for the actual symptoms," he said.

Dr. Johnson has been an adviser or consultant for Siemens Healthcare Diagnostics, Genzyme, and Piramal Healthcare. He has received research funding from Avid Radiopharmaceuticals, Eli Lilly, and other companies.

[email protected]

On Twitter @alz_gal

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]

Adults aged 65 years and older should receive both a conjugate and polysaccharide vaccine against pneumococcal pneumonia, according to a new federal proposal.

By a vote of 13-2, a working group of the Advisory Committee on Immunization Practices agreed that a combination of the pneumococcal 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) will provide the most complete protection for older patients.

For those who have never been vaccinated against pneumococcal pneumonia, or who aren’t sure of their vaccination status, the preferred sequence would be PCV13 first, followed by the PPSV23 vaccine within a minimum of 6-12 months – although that time frame should be considered a very flexible one. But the recommendation also accommodates people who have already had either vaccine, experts advised at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Those who have had PCV13 should get the PPSV23 within the 6-12 month framework if possible; the two vaccines should not be coadministered.

Those who have been vaccinated with PPSV23 only should receive the PCV13 at least 1 year later. High-risk patients who require an additional dose can receive another PPSV23 6-12 months after PCV13 vaccination.

The recommendation will be passed on to the full committee at its meeting in late October. It was made in a special interim meeting, during which the committee considered evidence provided by the randomized, controlled CAPITA study, and additional information on how herd immunization effects in younger people could impact the vulnerability of older people.

Although the clinical recommendation was made by a body of the Centers for Disease Control and Prevention, the federal body controlling reimbursement has extant policies that could limit its practical implementation. Medicare currently pays for only one pneumococcal pneumonia vaccine for adults aged 65 years and older. Although the Centers for Medicare & Medicaid Services (CMS) would consider amending that if the recommendation is adopted, any change would not be quick, a representative said.

"If CMS decided to go with a change in coverage for a two-shot regimen, that does take time," said Dr. Joseph Chin, medical officer for the agency’s Coverage and Analysis Group.

In most cases, the initial topic is addressed at the beginning of the year, followed by a period of public comment.

"The final okay is typically given in November, and the change is effective in January," Dr. Chin said.

Results of the CAPITA study, sponsored by Pfizer, which manufactures the vaccine, were released in March.

It concluded that the PCV13 vaccine offered significant protection against community-acquired pneumonia caused by strains in the vaccine, with 45% fewer episodes than in those who got the placebo.

There were also 45% fewer first episodes of nonbacteremic and noninvasive pneumonias and 75% fewer first episodes of invasive pneumonia, compared with placebo. The safety profile was good, and, according to the working group, the cost/benefit analysis is in line with other treatments that are considered cost-effective.

None of the committee members had any personal financial disclosures.

[email protected]