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Guideline update shortens minimum DAPT duration in CAD
New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.
The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.
The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).
The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.
The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.
The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.
The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.
The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.
The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.
These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.
Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.
New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.
The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.
The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).
The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.
The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.
The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.
The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.
The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.
The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.
These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.
Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.
New guidelines decrease the minimum duration of dual-antiplatelet therapy (DAPT) to as little as 3 months after drug-eluting stent placement in certain lower-risk patients with coronary artery disease.
The updated recommendations harmonize and replace six other guidelines, and apply to everolimus and zotarolimus stents, not Cypher or Taxus stents, said Dr. Eric R. Bates, who helped author the American College of Cardiology/American Heart Association Focused Update. “The emphasis is on balancing ischemic risk versus bleeding risk. The recommendations give clinicians guideline coverage to make personalized DAPT recommendations,” he said in an interview.
The guidance reflects recent evidence that shorter duration (3-6 months) of DAPT, compared with the standard 12 months of therapy does not increase the risk of stent thrombosis and potentially lessens bleeding risk in select patients. Other studies of an additional 18 or 36 months of DAPT found a decrease in the risk of MI and stent thrombosis, at the cost of greater risk of bleeding. Thus, the updated guidelines call for “a thoughtful assessment of the benefit-risk ratio, integration of study data, and consideration of patient preference” when selecting duration of DAPT. “In general, shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk, whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk,” the authors wrote, led by Dr. Glenn N. Levineof Baylor College of Medicine, Houston (J Am Coll Cardiol. 2016 Mar 29. doi: 10.1016/j.jacc.2016.03.512).
The recommendations define DAPT as combination therapy with aspirin and a P2Y12 receptor inhibitor – that is, clopidogrel, prasugrel, or ticagrelor. “When indicated, ticagrelor and prasugrel have a Class IIa preference over clopidogrel,” Dr. Bates said. The recommended daily dose of aspirin is 81 mg (range, 75-100 mg), which is usually continued indefinitely, regardless of how long patients receive dual therapy.
The shortened durations of dual-antiplatelet therapy include several scenarios. For elective percutaneous coronary intervention, the former Class I recommendation for 12 months of DAPT has been reduced to 6 months, with a Class IIb recommendation for either longer treatment or shorter (3-month) treatment, Dr. Bates, professor of medicine at the University of Michigan Health System in Ann Arbor, said. For patients with acute coronary syndrome, the guidelines retain the Class I recommendation for 12 months of DAPT, but also add a Class IIb recommendation for longer or shorter (6 months) DAPT.
The guidelines also include a new Class IIb recommendation for 12 months of DAPT started early after coronary artery bypass graft in patients with stable ischemic heart disease. This strategy “may be reasonable to improve vein graft patency” in these patients, the recommendations state.
The guidance clarifies previous recommendations on the timing of elective noncardiac surgery, and assigns Class IIb support for consideration of such surgeries starting 3 months after implantation of drug-eluting stents, if the risks of delaying surgery outweigh the expected risk of stent thrombosis when it is necessary to stop P2Y12 inhibitor therapy.
The recommendations now distinguish between B and C levels of evidence to increase granularity, according to Dr. Bates. The document updates recommendations on duration of DAPT across six previously published guidelines – the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (PCI); the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery; the 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease; the 2013ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction; the 2014 ACC/AHA Guideline for Non-ST-Elevation Acute Coronary Syndromes, and the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.
The extensive evidence review that informed guideline development was simultaneously reported by Dr. John Bittl at Munroe Regional Medical Center in Ocala, Fla., and his colleagues. The investigators synthesized evidence from 11 randomized controlled trials of more than 33,000 patients who received mainly newer generation stents. They also reviewed a randomized controlled trial of more than 21,000 patients with stable ischemic heart disease who were more than 1 year post-MI, and a post hoc analysis of a trial of more than 15,000 such patients.
These reviews uncovered “moderately strong evidence” that prolonged DAPT after implantation of newer generation drug-eluting stents “entails a trade-off between reductions in stent thrombosis and MI and increases in major hemorrhage,” Dr. Bittl and his colleagues wrote. Likewise, they found moderately strong evidence that prolonged DAPT helps prevent cardiovascular events at the cost of increased bleeding in patients whose coronary thrombotic risk stemmed from prior MI, not stent implantation. They found weak evidence of increased mortality in stent patients who received prolonged DAPT.
Dr. Bates reported consulting relationships with Merck and AstraZeneca. Eight other coauthors disclosed financial relationships with a number of pharmaceutical or device companies. Dr. Glenn Levine and seven coauthors disclosed no relationships with industry.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Endoscopic techniques provide organ-sparing options for myotomy, resection, and more
Minimally invasive endoscopic procedures are transforming gastrointestinal surgery by offering organ-sparing approaches for a range of pathologies. At the 2016 AGA Tech Summit, Dr. David Rattner updated attendees on three of these techniques – endoscopic submucosal dissection (ESD), peroral endoscopic myotomy (POEM), and endoscopic full-thickness resection (EFTR).
“It is likely that endoluminal treatments, combined with better understanding of molecular pathology, will decrease the need for radical surgical procedures for some common gastrointestinal conditions,” he said in an interview before the meeting, which is sponsored by the AGA Center for GI Innovation and Technology. Dr. Rattner is chief of the division of gastrointestinal and general surgery at Massachusetts General Hospital in Boston.
Dr. Jose Martinez put transorifice surgery in historical perspective and pointed the way forward in an accompanying presentation. “The collaboration with physicians and industry has really started to come along with the natural orifice approach,” said Dr. Martinez, professor of surgery at the University of Miami Health System.
Developed in the 1980s and substantially refined in the mid-2000s, ESD pioneered the endoscopic resection of entire intramucosal tumors without the need for open surgery. In a recent meta-analysis, ESD achieved significantly higher rates of en bloc resection than endoscopic mucosal resection (EMR), with significantly lower rates of local recurrence and comparable complication rates (World J Gastroenterol. 2014;20:8282-7).
ESD involves resecting the mucosa and much of the submucosa, while conserving the muscular layer of the esophagus. In contrast, during POEM, the surgeon intentionally divides the muscular layer, while the intact mucosa provides the barrier between the mediastinum or peritoneum and the esophageal lumen. The defining feature of POEM is the creation of a submucosal tunnel to access the muscle layer for myotomy without incising the skin.
POEM has been found highly successful for treating esophageal achalasia. In fact, in a recently published series of 500 cases, the success rate was 100%, even though the cohort included elderly patients and those with sigmoid esophagus and complex treatment histories (J Am Coll Surg. 2015;221:256-64). Two months post-treatment, average Eckardt scores had decreased by an average of 5.0, and lower esophageal sphincter pressures had fallen by nearly 50%. The adverse event rate was 3%, there were no fatalities, and improvements persisted 3 years later. “Nationwide, numerous centers have incorporated this technique and gotten significant positive results,” said Dr. Martinez.
“POEM will be shown to be as effective as any other currently existing therapy for the treatment of achalasia,” emphasized Dr. Rattner. Indeed, its success has sparked investigations of submucosal tunneling for other indications, such as tumor resection and pyloromyotomy for gastroparesis (World J Gastroenterol. 2014;20:17746-55).
Another cutting-edge technique is EFTR, described as a powerful tool not only for acquiring diagnostic tissue, but also for sparing some patients from surgery. Compared with ESD, it has the potential for higher diagnostic yield of full-thickness specimens, such as in cases of nonlifting adenomas, adenomas at difficult anatomic locations, T1-carcinomas, or submucosal colorectal tumors. For years, a lack of safe techniques and devices kept EFTR from entering routine clinical practice. But intensive research on natural orifice translumenal endoscopic surgery (NOTES) has helped propel innovations such as over-the-scope clips for closing incisions, and smaller, more maneuverable, over-the-scope full-thickness resection devices. Large-scale trials of EFTR are lacking, but in a recent report of 19 consecutive colonic submucosal tumors, EFTR enabled the removal of the entire tumor with capsule intact in 18 instances (Endoscopy. 2013;45[09]:770-3). Notably, colonic wall defects could be closed endoscopically in 16 of 18 cases.
“We are still a ways away from being able to perform EFTR on a routine basis, but new technologies are under development that will make this possible,” said Dr. Rattner. Agreeing that the future of transorifice surgery is bright and growing, Dr. Martinez said, “Strictures, obstructions, bleeding, foreign bodies are now fully resolved through endoscopic approaches.”
Minimally invasive endoscopic procedures are transforming gastrointestinal surgery by offering organ-sparing approaches for a range of pathologies. At the 2016 AGA Tech Summit, Dr. David Rattner updated attendees on three of these techniques – endoscopic submucosal dissection (ESD), peroral endoscopic myotomy (POEM), and endoscopic full-thickness resection (EFTR).
“It is likely that endoluminal treatments, combined with better understanding of molecular pathology, will decrease the need for radical surgical procedures for some common gastrointestinal conditions,” he said in an interview before the meeting, which is sponsored by the AGA Center for GI Innovation and Technology. Dr. Rattner is chief of the division of gastrointestinal and general surgery at Massachusetts General Hospital in Boston.
Dr. Jose Martinez put transorifice surgery in historical perspective and pointed the way forward in an accompanying presentation. “The collaboration with physicians and industry has really started to come along with the natural orifice approach,” said Dr. Martinez, professor of surgery at the University of Miami Health System.
Developed in the 1980s and substantially refined in the mid-2000s, ESD pioneered the endoscopic resection of entire intramucosal tumors without the need for open surgery. In a recent meta-analysis, ESD achieved significantly higher rates of en bloc resection than endoscopic mucosal resection (EMR), with significantly lower rates of local recurrence and comparable complication rates (World J Gastroenterol. 2014;20:8282-7).
ESD involves resecting the mucosa and much of the submucosa, while conserving the muscular layer of the esophagus. In contrast, during POEM, the surgeon intentionally divides the muscular layer, while the intact mucosa provides the barrier between the mediastinum or peritoneum and the esophageal lumen. The defining feature of POEM is the creation of a submucosal tunnel to access the muscle layer for myotomy without incising the skin.
POEM has been found highly successful for treating esophageal achalasia. In fact, in a recently published series of 500 cases, the success rate was 100%, even though the cohort included elderly patients and those with sigmoid esophagus and complex treatment histories (J Am Coll Surg. 2015;221:256-64). Two months post-treatment, average Eckardt scores had decreased by an average of 5.0, and lower esophageal sphincter pressures had fallen by nearly 50%. The adverse event rate was 3%, there were no fatalities, and improvements persisted 3 years later. “Nationwide, numerous centers have incorporated this technique and gotten significant positive results,” said Dr. Martinez.
“POEM will be shown to be as effective as any other currently existing therapy for the treatment of achalasia,” emphasized Dr. Rattner. Indeed, its success has sparked investigations of submucosal tunneling for other indications, such as tumor resection and pyloromyotomy for gastroparesis (World J Gastroenterol. 2014;20:17746-55).
Another cutting-edge technique is EFTR, described as a powerful tool not only for acquiring diagnostic tissue, but also for sparing some patients from surgery. Compared with ESD, it has the potential for higher diagnostic yield of full-thickness specimens, such as in cases of nonlifting adenomas, adenomas at difficult anatomic locations, T1-carcinomas, or submucosal colorectal tumors. For years, a lack of safe techniques and devices kept EFTR from entering routine clinical practice. But intensive research on natural orifice translumenal endoscopic surgery (NOTES) has helped propel innovations such as over-the-scope clips for closing incisions, and smaller, more maneuverable, over-the-scope full-thickness resection devices. Large-scale trials of EFTR are lacking, but in a recent report of 19 consecutive colonic submucosal tumors, EFTR enabled the removal of the entire tumor with capsule intact in 18 instances (Endoscopy. 2013;45[09]:770-3). Notably, colonic wall defects could be closed endoscopically in 16 of 18 cases.
“We are still a ways away from being able to perform EFTR on a routine basis, but new technologies are under development that will make this possible,” said Dr. Rattner. Agreeing that the future of transorifice surgery is bright and growing, Dr. Martinez said, “Strictures, obstructions, bleeding, foreign bodies are now fully resolved through endoscopic approaches.”
Minimally invasive endoscopic procedures are transforming gastrointestinal surgery by offering organ-sparing approaches for a range of pathologies. At the 2016 AGA Tech Summit, Dr. David Rattner updated attendees on three of these techniques – endoscopic submucosal dissection (ESD), peroral endoscopic myotomy (POEM), and endoscopic full-thickness resection (EFTR).
“It is likely that endoluminal treatments, combined with better understanding of molecular pathology, will decrease the need for radical surgical procedures for some common gastrointestinal conditions,” he said in an interview before the meeting, which is sponsored by the AGA Center for GI Innovation and Technology. Dr. Rattner is chief of the division of gastrointestinal and general surgery at Massachusetts General Hospital in Boston.
Dr. Jose Martinez put transorifice surgery in historical perspective and pointed the way forward in an accompanying presentation. “The collaboration with physicians and industry has really started to come along with the natural orifice approach,” said Dr. Martinez, professor of surgery at the University of Miami Health System.
Developed in the 1980s and substantially refined in the mid-2000s, ESD pioneered the endoscopic resection of entire intramucosal tumors without the need for open surgery. In a recent meta-analysis, ESD achieved significantly higher rates of en bloc resection than endoscopic mucosal resection (EMR), with significantly lower rates of local recurrence and comparable complication rates (World J Gastroenterol. 2014;20:8282-7).
ESD involves resecting the mucosa and much of the submucosa, while conserving the muscular layer of the esophagus. In contrast, during POEM, the surgeon intentionally divides the muscular layer, while the intact mucosa provides the barrier between the mediastinum or peritoneum and the esophageal lumen. The defining feature of POEM is the creation of a submucosal tunnel to access the muscle layer for myotomy without incising the skin.
POEM has been found highly successful for treating esophageal achalasia. In fact, in a recently published series of 500 cases, the success rate was 100%, even though the cohort included elderly patients and those with sigmoid esophagus and complex treatment histories (J Am Coll Surg. 2015;221:256-64). Two months post-treatment, average Eckardt scores had decreased by an average of 5.0, and lower esophageal sphincter pressures had fallen by nearly 50%. The adverse event rate was 3%, there were no fatalities, and improvements persisted 3 years later. “Nationwide, numerous centers have incorporated this technique and gotten significant positive results,” said Dr. Martinez.
“POEM will be shown to be as effective as any other currently existing therapy for the treatment of achalasia,” emphasized Dr. Rattner. Indeed, its success has sparked investigations of submucosal tunneling for other indications, such as tumor resection and pyloromyotomy for gastroparesis (World J Gastroenterol. 2014;20:17746-55).
Another cutting-edge technique is EFTR, described as a powerful tool not only for acquiring diagnostic tissue, but also for sparing some patients from surgery. Compared with ESD, it has the potential for higher diagnostic yield of full-thickness specimens, such as in cases of nonlifting adenomas, adenomas at difficult anatomic locations, T1-carcinomas, or submucosal colorectal tumors. For years, a lack of safe techniques and devices kept EFTR from entering routine clinical practice. But intensive research on natural orifice translumenal endoscopic surgery (NOTES) has helped propel innovations such as over-the-scope clips for closing incisions, and smaller, more maneuverable, over-the-scope full-thickness resection devices. Large-scale trials of EFTR are lacking, but in a recent report of 19 consecutive colonic submucosal tumors, EFTR enabled the removal of the entire tumor with capsule intact in 18 instances (Endoscopy. 2013;45[09]:770-3). Notably, colonic wall defects could be closed endoscopically in 16 of 18 cases.
“We are still a ways away from being able to perform EFTR on a routine basis, but new technologies are under development that will make this possible,” said Dr. Rattner. Agreeing that the future of transorifice surgery is bright and growing, Dr. Martinez said, “Strictures, obstructions, bleeding, foreign bodies are now fully resolved through endoscopic approaches.”
AT THE 2016 AGA TECH SUMMIT
Studies underscore limits of Tdap vaccine
Replacing the first dose of acellular pertussis vaccine with its whole-cell predecessor could cut the rate of whooping cough by about 95% – including in neonates at greatest risk of severe outcomes, researchers reported March 28 in JAMA Pediatrics.
Their model also predicted 95% fewer lost quality-adjusted life-years under the combined (whole-cell and acellular) vaccination strategy – even after accounting for vaccine-related adverse events, said Dr. Benjamin Althouse of the Santa Fe Institute and New Mexico State University, Las Cruces, and his associates. “Although new pertussis vaccines combining the safety of acellular pertussis and the efficacy of whole-cell pertussis are in early development, [they are] still a number of years away from regulatory approval,” they wrote. “In the interim, switching to the combined strategy is an effective option for reducing the disease and mortality burdens of Bordetella pertussis.”
The Centers for Disease Control and Prevention currently recommends five doses of acellular pertussis vaccine between 2 months and 4 to 6 years old. Infants born in the 1990s during the switch from the whole-cell vaccine to the safer acellular vaccine often received an initial whole-cell dose, followed by acellular doses. These “primed” children had less than half the rate of whooping cough than children who received only the acellular vaccine, multiple studies later showed. Since then, U.S. pertussis rates have surged, with more than 48,000 cases reported in 2012. Waning immunity is one factor, but the acellular vaccine also failed to prevent secondary B. pertussis transmission in a study of nonhuman primates, Dr. Althouse and his associates noted (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0047).
They compared the efficacy and cost-effectiveness of the acellular vaccination schedule with a schedule in which the first dose was whole-cell vaccine and the next four doses were acellular vaccine. In a model fitted to pertussis data from 2012, incidence was about 95% lower (95% confidence interval, 91%-98%) with the combined strategy, and infection rates in neonates fell by 96% (95% CI, 92%-98%). Even after accounting for adverse events, loss of quality-adjusted life-years also fell by about 95%, and healthcare costs dropped by 94%, saving more than $142 million per year.
The acellular pertussis vaccine was licensed as a booster for adolescents and adults in 2005. Over the next several years, pertussis rates dropped faster among 11- to 18-year-olds than among other age groups (Arch Pediatr Adolesc Med. 2012;166:344-9). But that encouraging trend “abruptly reversed” in 2010, “corresponding directly to the aging of acellular pertussis-vaccinated cohorts” who were primed with the acellular vaccine, said the authors of a follow-up study also published March 28 in JAMA Pediatrics (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2015.4875).
For this study, Tami Skoff and Stacey Martin of the CDC analyzed all pertussis cases reported in the United States between 1990 and 2014. Between 1990 and 2003, rates rose from 1.7 to 4.0 cases per 100,000 individuals, and pertussis epidemics dominated later years, the researchers said. The acellular vaccine helped reverse infection rates among adolescents immediately after its introduction, but after 2010, infection rates rose faster among 11- to 18-year-olds than among all other age groups combined (slope, 0.5727; P less than .001). By 2014, adolescents had the highest infection rates of any group except infants under 1 year old, who had the highest pertussis incidence throughout the study period.
The findings “support the accumulating literature on waning acellular vaccine-induced immunity,” said the researchers. Because immunity with the acellular vaccine wanes after about 2 years, additional vaccinations are unlikely to have much impact, they noted. They also emphasized the importance of timely vaccination and vaccinating pregnant women to protect infants.
Dr. Althouse and his associates were funded by the National Science Foundation, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. Skoff and Martin reported no external funding sources. None of the investigators had disclosures.
Although it has been clear for several years that immunity following acellular pertussis vaccines wanes, the study [by Skoff and Martin] documents the effect at a population level. The bad news is that Tdap vaccination mostly [benefited] adolescents who, when they were infants, received at least some doses of the whole-cell pertussis vaccine when it was still in use. Now, as those cohorts are replaced by younger ones who only received acellular vaccines, pertussis is making a comeback. Several studies have shown that the immune responses to the 2 types of vaccine are quite different and unfortunately the response to acellular vaccines is inferior. We will continue to see a lot of pertussis until new vaccines are developed.
What can we do to protect older children and adults from pertussis while we wait for new vaccines? DeAngelis et al. suggest that we could achieve a dramatic reduction in pertussis cases by giving an initial priming dose of whole-cell vaccine in infancy, followed by the remainder of the vaccine series with acellular vaccine. These findings must be considered preliminary because the authors made a number of assumptions for which we have insufficient data.
Pertussis is back. While we consider alternative vaccination strategies and develop new vaccines, we can at least do a better job of preventing pertussis-related deaths in infants by immunizing women during each pregnancy. We know that is safe and effective and is being increasingly accepted by pregnant women. As for other strategies, which might include reintroducing whole-cell vaccines, we need to be sure parents are going to go along.
Dr. Mark H. Sawyer is at the Rady Children’s Hospital–San Diego. He had no disclosures. These comments are based on his editorial (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0157).
Although it has been clear for several years that immunity following acellular pertussis vaccines wanes, the study [by Skoff and Martin] documents the effect at a population level. The bad news is that Tdap vaccination mostly [benefited] adolescents who, when they were infants, received at least some doses of the whole-cell pertussis vaccine when it was still in use. Now, as those cohorts are replaced by younger ones who only received acellular vaccines, pertussis is making a comeback. Several studies have shown that the immune responses to the 2 types of vaccine are quite different and unfortunately the response to acellular vaccines is inferior. We will continue to see a lot of pertussis until new vaccines are developed.
What can we do to protect older children and adults from pertussis while we wait for new vaccines? DeAngelis et al. suggest that we could achieve a dramatic reduction in pertussis cases by giving an initial priming dose of whole-cell vaccine in infancy, followed by the remainder of the vaccine series with acellular vaccine. These findings must be considered preliminary because the authors made a number of assumptions for which we have insufficient data.
Pertussis is back. While we consider alternative vaccination strategies and develop new vaccines, we can at least do a better job of preventing pertussis-related deaths in infants by immunizing women during each pregnancy. We know that is safe and effective and is being increasingly accepted by pregnant women. As for other strategies, which might include reintroducing whole-cell vaccines, we need to be sure parents are going to go along.
Dr. Mark H. Sawyer is at the Rady Children’s Hospital–San Diego. He had no disclosures. These comments are based on his editorial (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0157).
Although it has been clear for several years that immunity following acellular pertussis vaccines wanes, the study [by Skoff and Martin] documents the effect at a population level. The bad news is that Tdap vaccination mostly [benefited] adolescents who, when they were infants, received at least some doses of the whole-cell pertussis vaccine when it was still in use. Now, as those cohorts are replaced by younger ones who only received acellular vaccines, pertussis is making a comeback. Several studies have shown that the immune responses to the 2 types of vaccine are quite different and unfortunately the response to acellular vaccines is inferior. We will continue to see a lot of pertussis until new vaccines are developed.
What can we do to protect older children and adults from pertussis while we wait for new vaccines? DeAngelis et al. suggest that we could achieve a dramatic reduction in pertussis cases by giving an initial priming dose of whole-cell vaccine in infancy, followed by the remainder of the vaccine series with acellular vaccine. These findings must be considered preliminary because the authors made a number of assumptions for which we have insufficient data.
Pertussis is back. While we consider alternative vaccination strategies and develop new vaccines, we can at least do a better job of preventing pertussis-related deaths in infants by immunizing women during each pregnancy. We know that is safe and effective and is being increasingly accepted by pregnant women. As for other strategies, which might include reintroducing whole-cell vaccines, we need to be sure parents are going to go along.
Dr. Mark H. Sawyer is at the Rady Children’s Hospital–San Diego. He had no disclosures. These comments are based on his editorial (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0157).
Replacing the first dose of acellular pertussis vaccine with its whole-cell predecessor could cut the rate of whooping cough by about 95% – including in neonates at greatest risk of severe outcomes, researchers reported March 28 in JAMA Pediatrics.
Their model also predicted 95% fewer lost quality-adjusted life-years under the combined (whole-cell and acellular) vaccination strategy – even after accounting for vaccine-related adverse events, said Dr. Benjamin Althouse of the Santa Fe Institute and New Mexico State University, Las Cruces, and his associates. “Although new pertussis vaccines combining the safety of acellular pertussis and the efficacy of whole-cell pertussis are in early development, [they are] still a number of years away from regulatory approval,” they wrote. “In the interim, switching to the combined strategy is an effective option for reducing the disease and mortality burdens of Bordetella pertussis.”
The Centers for Disease Control and Prevention currently recommends five doses of acellular pertussis vaccine between 2 months and 4 to 6 years old. Infants born in the 1990s during the switch from the whole-cell vaccine to the safer acellular vaccine often received an initial whole-cell dose, followed by acellular doses. These “primed” children had less than half the rate of whooping cough than children who received only the acellular vaccine, multiple studies later showed. Since then, U.S. pertussis rates have surged, with more than 48,000 cases reported in 2012. Waning immunity is one factor, but the acellular vaccine also failed to prevent secondary B. pertussis transmission in a study of nonhuman primates, Dr. Althouse and his associates noted (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0047).
They compared the efficacy and cost-effectiveness of the acellular vaccination schedule with a schedule in which the first dose was whole-cell vaccine and the next four doses were acellular vaccine. In a model fitted to pertussis data from 2012, incidence was about 95% lower (95% confidence interval, 91%-98%) with the combined strategy, and infection rates in neonates fell by 96% (95% CI, 92%-98%). Even after accounting for adverse events, loss of quality-adjusted life-years also fell by about 95%, and healthcare costs dropped by 94%, saving more than $142 million per year.
The acellular pertussis vaccine was licensed as a booster for adolescents and adults in 2005. Over the next several years, pertussis rates dropped faster among 11- to 18-year-olds than among other age groups (Arch Pediatr Adolesc Med. 2012;166:344-9). But that encouraging trend “abruptly reversed” in 2010, “corresponding directly to the aging of acellular pertussis-vaccinated cohorts” who were primed with the acellular vaccine, said the authors of a follow-up study also published March 28 in JAMA Pediatrics (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2015.4875).
For this study, Tami Skoff and Stacey Martin of the CDC analyzed all pertussis cases reported in the United States between 1990 and 2014. Between 1990 and 2003, rates rose from 1.7 to 4.0 cases per 100,000 individuals, and pertussis epidemics dominated later years, the researchers said. The acellular vaccine helped reverse infection rates among adolescents immediately after its introduction, but after 2010, infection rates rose faster among 11- to 18-year-olds than among all other age groups combined (slope, 0.5727; P less than .001). By 2014, adolescents had the highest infection rates of any group except infants under 1 year old, who had the highest pertussis incidence throughout the study period.
The findings “support the accumulating literature on waning acellular vaccine-induced immunity,” said the researchers. Because immunity with the acellular vaccine wanes after about 2 years, additional vaccinations are unlikely to have much impact, they noted. They also emphasized the importance of timely vaccination and vaccinating pregnant women to protect infants.
Dr. Althouse and his associates were funded by the National Science Foundation, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. Skoff and Martin reported no external funding sources. None of the investigators had disclosures.
Replacing the first dose of acellular pertussis vaccine with its whole-cell predecessor could cut the rate of whooping cough by about 95% – including in neonates at greatest risk of severe outcomes, researchers reported March 28 in JAMA Pediatrics.
Their model also predicted 95% fewer lost quality-adjusted life-years under the combined (whole-cell and acellular) vaccination strategy – even after accounting for vaccine-related adverse events, said Dr. Benjamin Althouse of the Santa Fe Institute and New Mexico State University, Las Cruces, and his associates. “Although new pertussis vaccines combining the safety of acellular pertussis and the efficacy of whole-cell pertussis are in early development, [they are] still a number of years away from regulatory approval,” they wrote. “In the interim, switching to the combined strategy is an effective option for reducing the disease and mortality burdens of Bordetella pertussis.”
The Centers for Disease Control and Prevention currently recommends five doses of acellular pertussis vaccine between 2 months and 4 to 6 years old. Infants born in the 1990s during the switch from the whole-cell vaccine to the safer acellular vaccine often received an initial whole-cell dose, followed by acellular doses. These “primed” children had less than half the rate of whooping cough than children who received only the acellular vaccine, multiple studies later showed. Since then, U.S. pertussis rates have surged, with more than 48,000 cases reported in 2012. Waning immunity is one factor, but the acellular vaccine also failed to prevent secondary B. pertussis transmission in a study of nonhuman primates, Dr. Althouse and his associates noted (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0047).
They compared the efficacy and cost-effectiveness of the acellular vaccination schedule with a schedule in which the first dose was whole-cell vaccine and the next four doses were acellular vaccine. In a model fitted to pertussis data from 2012, incidence was about 95% lower (95% confidence interval, 91%-98%) with the combined strategy, and infection rates in neonates fell by 96% (95% CI, 92%-98%). Even after accounting for adverse events, loss of quality-adjusted life-years also fell by about 95%, and healthcare costs dropped by 94%, saving more than $142 million per year.
The acellular pertussis vaccine was licensed as a booster for adolescents and adults in 2005. Over the next several years, pertussis rates dropped faster among 11- to 18-year-olds than among other age groups (Arch Pediatr Adolesc Med. 2012;166:344-9). But that encouraging trend “abruptly reversed” in 2010, “corresponding directly to the aging of acellular pertussis-vaccinated cohorts” who were primed with the acellular vaccine, said the authors of a follow-up study also published March 28 in JAMA Pediatrics (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2015.4875).
For this study, Tami Skoff and Stacey Martin of the CDC analyzed all pertussis cases reported in the United States between 1990 and 2014. Between 1990 and 2003, rates rose from 1.7 to 4.0 cases per 100,000 individuals, and pertussis epidemics dominated later years, the researchers said. The acellular vaccine helped reverse infection rates among adolescents immediately after its introduction, but after 2010, infection rates rose faster among 11- to 18-year-olds than among all other age groups combined (slope, 0.5727; P less than .001). By 2014, adolescents had the highest infection rates of any group except infants under 1 year old, who had the highest pertussis incidence throughout the study period.
The findings “support the accumulating literature on waning acellular vaccine-induced immunity,” said the researchers. Because immunity with the acellular vaccine wanes after about 2 years, additional vaccinations are unlikely to have much impact, they noted. They also emphasized the importance of timely vaccination and vaccinating pregnant women to protect infants.
Dr. Althouse and his associates were funded by the National Science Foundation, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. Skoff and Martin reported no external funding sources. None of the investigators had disclosures.
FROM JAMA PEDIATRICS
Key clinical point: Two studies underscored the problem of waning immunity with the acellular pertussis vaccine.
Major finding: Replacing the first dose of acellular pertussis vaccine with its whole-cell predecessor cut incidence by about 95% in a mathematical model. After 2010, pertussis infection rates rose faster among 11 to 18-year-olds than among all other age groups combined (slope, 0.5727; P less than .001).
Data source: Two separate analyses of national pertussis incidence data.
Disclosures: Dr. Althouse and his associates were funded by the National Science Foundation, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. Ms. Skoff and Ms. Martin reported no external funding sources. None of the investigators had disclosures.
FDA requires boxed warnings for short-acting opioids
The Food and Drug Administration will require boxed warnings on the risks of abuse, misuse, addiction, overdose, and death for all immediate-release opioids.
The decision is part of the latest wave of efforts by federal officials to combat the ballooning opioid epidemic. It comes a week after the Centers for Disease Control and Prevention issued guidelines recommending nonopioid analgesia for noncancer pain, and 3 years after FDA required boxed warnings for all extended-release opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs at the FDA Center for Drug Evaluation and Research, said during a news conference March 22.
The FDA has faced criticism for doing too little, too late to curtail opioid-related deaths, which have surpassed motor vehicle accidents as the leading cause of injury-related fatality in the United States. The agency initially limited its boxed warning to extended-release opioids because they contain more drug per tablet, are more attractive to substance abusers, and have a longer temporal risk of potentially fatal respiratory depression, Dr. Throckmorton said.
“This change will remind prescribers that immediate-release opioids are also powerful drugs with important safety concerns,” he said. “We will continue to monitor the situation, and as we need to do more, we will.”
The new boxed warning requirement affects 87 innovator products and 141 generic immediate-release opioids, whereas the 2013 decision involved just 8 long-acting products. The FDA notified manufacturers of its decision today and expects to finish reviewing label updates by the end of 2016, officials said.
In addition, all prescription opioids will be required to include warnings about potentially harmful drug interactions; serotonin syndrome; adrenal insufficiency and other endocrine problems; and neonatal opioid withdrawal syndrome, FDA Commissioner Dr. Robert Califf said during the press conference. While some pregnant women with chronic pain may need to stay on opioids, providers should be prepared to treat withdrawal syndrome in newborns, Dr. Throckmorton added.
The American Congress of Obstetricians and Gynecologists responded to the CDC guidelines and FDA announcement by advising women who are already taking opioids to consider staying on them during pregnancy. Neonatal opioid withdrawal is treatable and has not been clearly linked to long-term problems, while withdrawal during pregnancy can cause fetal demise, according to an ACOG statement.
Dr. Califf emphasized that the FDA does not intend to stop physicians from prescribing opioids to patients with serious pain.
Most physicians do not read labels, but label changes trigger discussions, which lead to formulary changes and updates to electronic prescription monitoring programs, he added. “That really starts with a label from the FDA. I can assure you the label will have an impact.”
The FDA will convene an advisory committee meeting on May 3 to May 4 to discuss the impact of boxed warnings for extended-release opioids and approvals of abuse-deterrent formulations, Dr. Throckmorton said. Advisers also will discuss whether to add immediate-release opioids to the existing Risk Evaluation and Mitigation Strategies (REMS) for extended-release formulations.
“The totality of these actions is what’s going to be needed for change,” Dr. Throckmorton said. “The labeling is an important part, but its not the only thing that’s going to be necessary.”
The Food and Drug Administration will require boxed warnings on the risks of abuse, misuse, addiction, overdose, and death for all immediate-release opioids.
The decision is part of the latest wave of efforts by federal officials to combat the ballooning opioid epidemic. It comes a week after the Centers for Disease Control and Prevention issued guidelines recommending nonopioid analgesia for noncancer pain, and 3 years after FDA required boxed warnings for all extended-release opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs at the FDA Center for Drug Evaluation and Research, said during a news conference March 22.
The FDA has faced criticism for doing too little, too late to curtail opioid-related deaths, which have surpassed motor vehicle accidents as the leading cause of injury-related fatality in the United States. The agency initially limited its boxed warning to extended-release opioids because they contain more drug per tablet, are more attractive to substance abusers, and have a longer temporal risk of potentially fatal respiratory depression, Dr. Throckmorton said.
“This change will remind prescribers that immediate-release opioids are also powerful drugs with important safety concerns,” he said. “We will continue to monitor the situation, and as we need to do more, we will.”
The new boxed warning requirement affects 87 innovator products and 141 generic immediate-release opioids, whereas the 2013 decision involved just 8 long-acting products. The FDA notified manufacturers of its decision today and expects to finish reviewing label updates by the end of 2016, officials said.
In addition, all prescription opioids will be required to include warnings about potentially harmful drug interactions; serotonin syndrome; adrenal insufficiency and other endocrine problems; and neonatal opioid withdrawal syndrome, FDA Commissioner Dr. Robert Califf said during the press conference. While some pregnant women with chronic pain may need to stay on opioids, providers should be prepared to treat withdrawal syndrome in newborns, Dr. Throckmorton added.
The American Congress of Obstetricians and Gynecologists responded to the CDC guidelines and FDA announcement by advising women who are already taking opioids to consider staying on them during pregnancy. Neonatal opioid withdrawal is treatable and has not been clearly linked to long-term problems, while withdrawal during pregnancy can cause fetal demise, according to an ACOG statement.
Dr. Califf emphasized that the FDA does not intend to stop physicians from prescribing opioids to patients with serious pain.
Most physicians do not read labels, but label changes trigger discussions, which lead to formulary changes and updates to electronic prescription monitoring programs, he added. “That really starts with a label from the FDA. I can assure you the label will have an impact.”
The FDA will convene an advisory committee meeting on May 3 to May 4 to discuss the impact of boxed warnings for extended-release opioids and approvals of abuse-deterrent formulations, Dr. Throckmorton said. Advisers also will discuss whether to add immediate-release opioids to the existing Risk Evaluation and Mitigation Strategies (REMS) for extended-release formulations.
“The totality of these actions is what’s going to be needed for change,” Dr. Throckmorton said. “The labeling is an important part, but its not the only thing that’s going to be necessary.”
The Food and Drug Administration will require boxed warnings on the risks of abuse, misuse, addiction, overdose, and death for all immediate-release opioids.
The decision is part of the latest wave of efforts by federal officials to combat the ballooning opioid epidemic. It comes a week after the Centers for Disease Control and Prevention issued guidelines recommending nonopioid analgesia for noncancer pain, and 3 years after FDA required boxed warnings for all extended-release opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs at the FDA Center for Drug Evaluation and Research, said during a news conference March 22.
The FDA has faced criticism for doing too little, too late to curtail opioid-related deaths, which have surpassed motor vehicle accidents as the leading cause of injury-related fatality in the United States. The agency initially limited its boxed warning to extended-release opioids because they contain more drug per tablet, are more attractive to substance abusers, and have a longer temporal risk of potentially fatal respiratory depression, Dr. Throckmorton said.
“This change will remind prescribers that immediate-release opioids are also powerful drugs with important safety concerns,” he said. “We will continue to monitor the situation, and as we need to do more, we will.”
The new boxed warning requirement affects 87 innovator products and 141 generic immediate-release opioids, whereas the 2013 decision involved just 8 long-acting products. The FDA notified manufacturers of its decision today and expects to finish reviewing label updates by the end of 2016, officials said.
In addition, all prescription opioids will be required to include warnings about potentially harmful drug interactions; serotonin syndrome; adrenal insufficiency and other endocrine problems; and neonatal opioid withdrawal syndrome, FDA Commissioner Dr. Robert Califf said during the press conference. While some pregnant women with chronic pain may need to stay on opioids, providers should be prepared to treat withdrawal syndrome in newborns, Dr. Throckmorton added.
The American Congress of Obstetricians and Gynecologists responded to the CDC guidelines and FDA announcement by advising women who are already taking opioids to consider staying on them during pregnancy. Neonatal opioid withdrawal is treatable and has not been clearly linked to long-term problems, while withdrawal during pregnancy can cause fetal demise, according to an ACOG statement.
Dr. Califf emphasized that the FDA does not intend to stop physicians from prescribing opioids to patients with serious pain.
Most physicians do not read labels, but label changes trigger discussions, which lead to formulary changes and updates to electronic prescription monitoring programs, he added. “That really starts with a label from the FDA. I can assure you the label will have an impact.”
The FDA will convene an advisory committee meeting on May 3 to May 4 to discuss the impact of boxed warnings for extended-release opioids and approvals of abuse-deterrent formulations, Dr. Throckmorton said. Advisers also will discuss whether to add immediate-release opioids to the existing Risk Evaluation and Mitigation Strategies (REMS) for extended-release formulations.
“The totality of these actions is what’s going to be needed for change,” Dr. Throckmorton said. “The labeling is an important part, but its not the only thing that’s going to be necessary.”
In vivo tau imaging correlated with Braak stages in older adults
PET imaging studies of aging brains revealed uptake of a radiolabeled tau tracer that correlated with the Braak stages of tau pathology in Alzheimer’s disease, according to two studies published online in Neuron and Brain.
The findings show that PET can be used to track tau deposition in living humans, “with results that confirm and extend information obtained from neuropathological studies,” wrote Michael Schöll, Ph.D., of the Helen Wills Neuroscience Institute at the University of California, Berkeley. Age and beta-amyloid deposition on PET imaging with Pittsburgh compound B also were associated with distinct patterns of tau deposition, which in the medial temporal lobe was tied to episodic age-related memory decline, he and his associates reported in Neuron. “The relationship between tau and cognition, even in cognitively normal older people, suggests a crucial role for this protein in aging, supporting the use of tau imaging in naturalistic studies and therapeutic trials,” they added.
Tau pathology occurs in Alzheimer’s disease, but also characterizes normal cognitive aging. Previously, the relationships between age, beta-amyloid, and tau protein accumulation had only been studied in cerebrospinal fluid, postmortem brain tissue, and animals, Dr. Schöll and his coinvestigators said. Using open source software (Freesurfer), they delineated brain regions that correlated anatomically with the histopathologically defined Braak stages of Alzheimer’s disease. Then they used PET to characterize uptake of 18F-AV-1451, a radioligand for tau, in 53 adults. A total of 5 participants were 20-26 years old, 33 were cognitively healthy older adults aged 64-90 years, and 15 were 53-77 years old and had suspected Alzheimer’s disease (Neuron. 2016;89[5]:971-82).
Older age predicted tau deposition in the medial temporal lobe and in the basal forebrain and insula, the investigators found. In cognitively healthy older adults, worse performance on a word recall test of episodic memory was associated with tau deposition in regions of the medial temporal lobe regions that are affected in Braak stages I and II. Age-related tau deposition in the medial temporal lobe seemed to be independent of beta-amyloid accumulation, but tau deposition in other isocortical regions required the presence of cortical beta-amyloid, and was associated with lower global cognition. “Our results suggest that tau deposition, especially in the medial temporal lobe, is an important aspect of cognitive aging that may have behavioral consequences. They also suggest a relationship between tau and beta-amyloid, with implications for Alzheimer’s disease pathogenesis,” said the investigators.
Patients with Alzheimer’s disease had increased tau deposition in early and middle Braak stage regions, which often involved larger areas of the medial and lateral parietal and, to a lesser extent, frontal lobes, the investigators also reported. “This was consistent with Braak stage V/VI, which was confirmed by our in vivo Braak staging,” they added.
In the second study, Adam Schwarz, Ph.D., of Eli Lilly and Company, Indianapolis, and his associates performed 18F-AV-1451 PET scans of 14 controls aged 21-39 years and 173 adults aged 50-95 years, of which 42 were cognitively normal, 87 had mild cognitive impairment, and 44 had Alzheimer’s disease. As in the first study, the investigators defined brain regions that closely approximated those traditionally associated with Braak stages 0 through VI. Then they estimated the Braak stage for each subject based on individual PET results (Brain. 2016 Mar 2. doi: 10.1093/brain/aww023).
The researchers estimated Braak stages corresponding to stereotypical progression patterns in 149 (86%) of the 173 test subjects, while another 12 (7%) had relative sparing of the hippocampus, occipital lobe, or both, but fit predefined variants (2 with atypical Braak stage IV and 10 with atypical Braak stage V profiles). The remaining 12 (7%) did not fit any of the stereotypical or variant profiles in either brain hemisphere. Estimated Braak stage was significantly associated with amyloid status, diagnostic category, and measures of global cognition. “We demonstrated the presence of anatomical profiles of increased 18F-AV-1451 binding that strongly mirrored the stereotypical spread and progression of tau pathology that is encapsulated in the Braak staging scheme,” the researchers concluded.
The work by Dr. Schöll and associates was supported by the National Institutes of Health, the Swedish Medical Association, Tau Consortium, Blanceflor Foundation, John Douglas French Alzheimer’s Foundation, Marie Curie FP7 International Outgoing Fellowship, and BrightFocus Foundation. The tracer was used with the permission of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. Dr. Schöll had no disclosures, and two coinvestigators reported relationships with Avid, Bioclinica, Genentech, and Novartis.
Dr. Schwarz and his coauthors all reported current employment with either Eli Lilly or Avid Radiopharmaceuticals.
PET imaging studies of aging brains revealed uptake of a radiolabeled tau tracer that correlated with the Braak stages of tau pathology in Alzheimer’s disease, according to two studies published online in Neuron and Brain.
The findings show that PET can be used to track tau deposition in living humans, “with results that confirm and extend information obtained from neuropathological studies,” wrote Michael Schöll, Ph.D., of the Helen Wills Neuroscience Institute at the University of California, Berkeley. Age and beta-amyloid deposition on PET imaging with Pittsburgh compound B also were associated with distinct patterns of tau deposition, which in the medial temporal lobe was tied to episodic age-related memory decline, he and his associates reported in Neuron. “The relationship between tau and cognition, even in cognitively normal older people, suggests a crucial role for this protein in aging, supporting the use of tau imaging in naturalistic studies and therapeutic trials,” they added.
Tau pathology occurs in Alzheimer’s disease, but also characterizes normal cognitive aging. Previously, the relationships between age, beta-amyloid, and tau protein accumulation had only been studied in cerebrospinal fluid, postmortem brain tissue, and animals, Dr. Schöll and his coinvestigators said. Using open source software (Freesurfer), they delineated brain regions that correlated anatomically with the histopathologically defined Braak stages of Alzheimer’s disease. Then they used PET to characterize uptake of 18F-AV-1451, a radioligand for tau, in 53 adults. A total of 5 participants were 20-26 years old, 33 were cognitively healthy older adults aged 64-90 years, and 15 were 53-77 years old and had suspected Alzheimer’s disease (Neuron. 2016;89[5]:971-82).
Older age predicted tau deposition in the medial temporal lobe and in the basal forebrain and insula, the investigators found. In cognitively healthy older adults, worse performance on a word recall test of episodic memory was associated with tau deposition in regions of the medial temporal lobe regions that are affected in Braak stages I and II. Age-related tau deposition in the medial temporal lobe seemed to be independent of beta-amyloid accumulation, but tau deposition in other isocortical regions required the presence of cortical beta-amyloid, and was associated with lower global cognition. “Our results suggest that tau deposition, especially in the medial temporal lobe, is an important aspect of cognitive aging that may have behavioral consequences. They also suggest a relationship between tau and beta-amyloid, with implications for Alzheimer’s disease pathogenesis,” said the investigators.
Patients with Alzheimer’s disease had increased tau deposition in early and middle Braak stage regions, which often involved larger areas of the medial and lateral parietal and, to a lesser extent, frontal lobes, the investigators also reported. “This was consistent with Braak stage V/VI, which was confirmed by our in vivo Braak staging,” they added.
In the second study, Adam Schwarz, Ph.D., of Eli Lilly and Company, Indianapolis, and his associates performed 18F-AV-1451 PET scans of 14 controls aged 21-39 years and 173 adults aged 50-95 years, of which 42 were cognitively normal, 87 had mild cognitive impairment, and 44 had Alzheimer’s disease. As in the first study, the investigators defined brain regions that closely approximated those traditionally associated with Braak stages 0 through VI. Then they estimated the Braak stage for each subject based on individual PET results (Brain. 2016 Mar 2. doi: 10.1093/brain/aww023).
The researchers estimated Braak stages corresponding to stereotypical progression patterns in 149 (86%) of the 173 test subjects, while another 12 (7%) had relative sparing of the hippocampus, occipital lobe, or both, but fit predefined variants (2 with atypical Braak stage IV and 10 with atypical Braak stage V profiles). The remaining 12 (7%) did not fit any of the stereotypical or variant profiles in either brain hemisphere. Estimated Braak stage was significantly associated with amyloid status, diagnostic category, and measures of global cognition. “We demonstrated the presence of anatomical profiles of increased 18F-AV-1451 binding that strongly mirrored the stereotypical spread and progression of tau pathology that is encapsulated in the Braak staging scheme,” the researchers concluded.
The work by Dr. Schöll and associates was supported by the National Institutes of Health, the Swedish Medical Association, Tau Consortium, Blanceflor Foundation, John Douglas French Alzheimer’s Foundation, Marie Curie FP7 International Outgoing Fellowship, and BrightFocus Foundation. The tracer was used with the permission of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. Dr. Schöll had no disclosures, and two coinvestigators reported relationships with Avid, Bioclinica, Genentech, and Novartis.
Dr. Schwarz and his coauthors all reported current employment with either Eli Lilly or Avid Radiopharmaceuticals.
PET imaging studies of aging brains revealed uptake of a radiolabeled tau tracer that correlated with the Braak stages of tau pathology in Alzheimer’s disease, according to two studies published online in Neuron and Brain.
The findings show that PET can be used to track tau deposition in living humans, “with results that confirm and extend information obtained from neuropathological studies,” wrote Michael Schöll, Ph.D., of the Helen Wills Neuroscience Institute at the University of California, Berkeley. Age and beta-amyloid deposition on PET imaging with Pittsburgh compound B also were associated with distinct patterns of tau deposition, which in the medial temporal lobe was tied to episodic age-related memory decline, he and his associates reported in Neuron. “The relationship between tau and cognition, even in cognitively normal older people, suggests a crucial role for this protein in aging, supporting the use of tau imaging in naturalistic studies and therapeutic trials,” they added.
Tau pathology occurs in Alzheimer’s disease, but also characterizes normal cognitive aging. Previously, the relationships between age, beta-amyloid, and tau protein accumulation had only been studied in cerebrospinal fluid, postmortem brain tissue, and animals, Dr. Schöll and his coinvestigators said. Using open source software (Freesurfer), they delineated brain regions that correlated anatomically with the histopathologically defined Braak stages of Alzheimer’s disease. Then they used PET to characterize uptake of 18F-AV-1451, a radioligand for tau, in 53 adults. A total of 5 participants were 20-26 years old, 33 were cognitively healthy older adults aged 64-90 years, and 15 were 53-77 years old and had suspected Alzheimer’s disease (Neuron. 2016;89[5]:971-82).
Older age predicted tau deposition in the medial temporal lobe and in the basal forebrain and insula, the investigators found. In cognitively healthy older adults, worse performance on a word recall test of episodic memory was associated with tau deposition in regions of the medial temporal lobe regions that are affected in Braak stages I and II. Age-related tau deposition in the medial temporal lobe seemed to be independent of beta-amyloid accumulation, but tau deposition in other isocortical regions required the presence of cortical beta-amyloid, and was associated with lower global cognition. “Our results suggest that tau deposition, especially in the medial temporal lobe, is an important aspect of cognitive aging that may have behavioral consequences. They also suggest a relationship between tau and beta-amyloid, with implications for Alzheimer’s disease pathogenesis,” said the investigators.
Patients with Alzheimer’s disease had increased tau deposition in early and middle Braak stage regions, which often involved larger areas of the medial and lateral parietal and, to a lesser extent, frontal lobes, the investigators also reported. “This was consistent with Braak stage V/VI, which was confirmed by our in vivo Braak staging,” they added.
In the second study, Adam Schwarz, Ph.D., of Eli Lilly and Company, Indianapolis, and his associates performed 18F-AV-1451 PET scans of 14 controls aged 21-39 years and 173 adults aged 50-95 years, of which 42 were cognitively normal, 87 had mild cognitive impairment, and 44 had Alzheimer’s disease. As in the first study, the investigators defined brain regions that closely approximated those traditionally associated with Braak stages 0 through VI. Then they estimated the Braak stage for each subject based on individual PET results (Brain. 2016 Mar 2. doi: 10.1093/brain/aww023).
The researchers estimated Braak stages corresponding to stereotypical progression patterns in 149 (86%) of the 173 test subjects, while another 12 (7%) had relative sparing of the hippocampus, occipital lobe, or both, but fit predefined variants (2 with atypical Braak stage IV and 10 with atypical Braak stage V profiles). The remaining 12 (7%) did not fit any of the stereotypical or variant profiles in either brain hemisphere. Estimated Braak stage was significantly associated with amyloid status, diagnostic category, and measures of global cognition. “We demonstrated the presence of anatomical profiles of increased 18F-AV-1451 binding that strongly mirrored the stereotypical spread and progression of tau pathology that is encapsulated in the Braak staging scheme,” the researchers concluded.
The work by Dr. Schöll and associates was supported by the National Institutes of Health, the Swedish Medical Association, Tau Consortium, Blanceflor Foundation, John Douglas French Alzheimer’s Foundation, Marie Curie FP7 International Outgoing Fellowship, and BrightFocus Foundation. The tracer was used with the permission of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. Dr. Schöll had no disclosures, and two coinvestigators reported relationships with Avid, Bioclinica, Genentech, and Novartis.
Dr. Schwarz and his coauthors all reported current employment with either Eli Lilly or Avid Radiopharmaceuticals.
FROM NEURON AND BRAIN
Key clinical point: Researchers used PET imaging to link uptake of a radioligand for the tau protein with the traditional Braak stages of tau pathology.
Major finding: Older age predicted tau deposition in the medial temporal lobe and in the basal forebrain and insula, while patients with Alzheimer’s disease had increased tau deposition in early and middle Braak stage regions, which often involved larger areas of the medial and lateral parietal and, to a lesser extent, frontal lobes.
Data source: Two separate studies of healthy young adults, older adults without a diagnosis of Alzheimer’s disease, and older adults with Alzheimer’s disease.
Disclosures: The work by Dr. Schöll and associates was supported by the National Institutes of Health, the Swedish Medical Association, Tau Consortium, Blanceflor Foundation, John Douglas French Alzheimer’s Foundation, Marie Curie FP7 International Outgoing Fellowship, and BrightFocus Foundation. The tracer was used with the permission of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. Dr. Schöll had no disclosures, and two coinvestigators reported relationships with Avid, Bioclinica, Genentech, and Novartis. Dr. Schwarz and his coauthors all reported current employment with either Eli Lilly or Avid Radiopharmaceuticals.
Coronary Artery Calcium Linked to Cancer, Kidney Disease, COPD
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
FROM JACC CARDIOVASCULAR IMAGING
Coronary artery calcium linked to cancer, kidney disease, COPD
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
The current report from the Multi-Ethnic Study of Atherosclerosis further expands the evidence base supporting the concept of coronary artery calcium as a marker of global health by examining its prognostic power across a diversity of noncardiovascular conditions.
Regardless of the directionality or magnitude of the connections between cardiovascular disease and non-CVD conditions, the extent to which coronary artery calcium–guided patient adherence to risk factor modification and lifestyle recommendations [affected] non-CVD conditions remains an additional link that should be explored further.
A synthesis of evidence, including the study by Handy et al., now supports the predictive ability of coronary artery calcium to estimate cardiac, cerebrovascular, and noncardiovascular conditions. We likely should come full circle in our discussion and acknowledge the far reaching implications of its predictive ability. Perhaps our index response that CAC should be fully integrated into all adult wellness and screening evaluations was on target after all!
Although CAC has not been without its critics and is not supported as a reimbursable procedure, its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide health care decision making.
Dr. Mosaab Awad, Dr. Parham Eshtehardi, and Leslee J. Shaw, Ph.D., of Emory University Clinical Cardiovascular Research Institute, Emory University, Atlanta, made these comments in an editorial (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.021). They had no disclosures.
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
Patients whose coronary artery calcium scores exceeded 400 were significantly more likely to develop cancer, chronic obstructive pulmonary disease, chronic kidney disease, and hip fractures, compared with adults with undetectable CAC, in an analysis of the Multi-Ethnic Study of Atherosclerosis reported March 9 in JACC Cardiovascular Imaging.
The study is the first to examine the relationship between CAC and significant noncardiovascular diseases, said Dr. Catherine Handy of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore. Patients with CAC scores of zero represent a unique group of “healthy agers,” she and her associates said. Conversely, 20% of initial non-CVD events occurred in the 10% of patients with CAC scores over 400, and 70% of events occurred in patients with scores greater than zero, they reported.
While CAC is an established indicator of vascular aging, CVD risk, and all-cause mortality, its relationship with non-CVD is unclear. To elucidate the issue, the researchers analyzed data from the prospective, observational Multi-Ethnic Study of Atherosclerosis, which included 6,814 adults aged 45-84 years from six U.S. cities. Patients had no CVD and were not receiving cancer treatment.
Over a median follow-up period of 10.2 years, and after controlling for demographic factors and predictors of CVD, patients with CAC scores exceeding 400 were significantly more likely to develop cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71) and hip fracture (HR, 4.29), compared with patients without detectable CAC. Patients with CAC scores of zero were at significantly lower risk of these diagnoses, compared with patients with scores greater than zero (JACC Cardiovasc Imaging. 2016 Mar 9. doi: 10.1016/j.jcmg.2015.09.02).
Doubling of CAC was a modest but significant predictor of cancer, chronic kidney disease, pneumonia, and chronic obstructive pulmonary disease in the subgroup of adults aged 65 years and older. However, CAC was not associated with dementia or deep vein thrombosis or pulmonary embolism.
Sparse diagnoses of hip fractures and DVT/PE meant that the study might be underpowered to clearly link CAC with risk of these events, said the researchers. There also might not have been enough follow-up time to uncover risk in participants with the lowest CAC scores, they said. “At this time, our data are not powered for stratifying results based on gender or race,” they added.
The National Institutes of Health funded the study. The researchers had no conflicts of interest.
FROM JACC CARDIOVASCULAR IMAGING
Key clinical point: High coronary artery calcium scores were significantly associated with noncardiovascular disease events in a prospective study.
Major finding: Patients with CAC scores exceeding 400 were at significantly greater risk of cancer (hazard ratio, 1.53), chronic kidney disease (HR, 1.70), pneumonia (HR, 1.97), chronic obstructive pulmonary disease (HR, 2.71), and hip fracture (HR, 4.29), compared with patients without detectable CAC.
Data source: A prospective, observational cohort study of 6,814 adults aged 45-84 years.
Disclosures: The National Institutes of Health funded the study. The researchers had no conflicts of interest.
Ultrasound bested tomosynthesis for screening dense breast tissue
Ultrasound was about 1.8 times more sensitive than tomosynthesis for the incremental detection of breast cancer in women with radiologically dense breasts and negative two-dimensional mammography screening, according to interim results from the first prospective trial to directly compare the two modalities.
“However, future application of adjunct screening should consider that tomosynthesis detected more than 50% of the additional breast cancers in these women, and could potentially be [a] primary screening modality,” wrote Dr. Alberto Tagliafico of the University of Genoa (Italy) and his associates. The study was published online March 9 in the Journal of Clinical Oncology and presented simultaneously at the European Breast Cancer Conference.
Radiologically dense breast tissue undermines the sensitivity of mammography and is itself an independent risk factor for breast cancer. Recently, many states began requiring that women be informed of their breast density and adjunct screening measures, such as ultrasound. But estimates of the sensitivity of ultrasound have ranged from about 1.9 to 4.2 cancers for every 1,000 screens, said the researchers. This variance, combined with costs and concerns about false-positive recalls, have fueled debates about the value of adjunct measures in breast cancer screening, they added. To help clarify these issues, the multicenter ASTOUND (Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts) study compared physician-performed ultrasound and tomosynthesis results for 3,231 asymptomatic women aged 44 to 71 years, whose median age was 51 years (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.63.4147).
In all, the researchers detected 24 additional breast cancers, 23 of which were invasive. Thus, ultrasound detected about 7.1 additional cancers for every 1,000 screens (95% confidence interval, 4.2-10), compared with 4.0 additional cancers per 1,000 screens for tomosynthesis (95% CI, 1.8-6.2; P = .006). Only one cancer was detected by tomosynthesis alone. The rate of false-positive recalls was similar for the two modalities – 53 cases for tomosynthesis, versus 63 for ultrasound (P = .26). Rates of false-positive recalls leading to biopsy also were similar. Needle biopsies usually sufficed in recalled cases, but two women underwent surgical biopsies, both of which revealed radial scars.
If the final results of ASTOUND confirm these interim data, “it could be argued that breast tomosynthesis has little value in a setting where adjunct ultrasound is frequently used for screening women with mammography-dense breasts,” said the researchers. But tomosynthesis may have a role as a primary screening modality in other setting, especially because tomosynthesis acquisitions that also provide reconstructed 2D mammography are now available, lessening concerns about unjustified radiation exposure, they added.
The “modest” number of cancers in the interim report led to relatively wide confidence intervals, the investigators noted. Biomarker data were not available for all cancers, and both prevalent and incident ultrasound data were compared with prevalent tomosynthesis data, which might bias false-positive recall results in favor of ultrasound, they added.
Currently, 24 American states have laws requiring that women receive some level of notification about breast density with their mammography results. Dense breast tissue can hide cancer on mammography, especially when the cancer lacks calcifications, resulting in delayed diagnosis and worse outcomes. Moreover, dense breast tissue is an independent risk factor for developing breast cancer.
Because the primary goal of screening is detection of early breast cancer, ultrasound would seem the clear choice, compared with tomosynthesis. Given comparable false-positive rates in ASTOUND, the estimated cost per cancer detected would be similar or more favorable for ultrasound than tomosynthesis. Ultrasound equipment is becoming much less expensive, requires no ionizing radiation, and it is easy to guide needle biopsy of lesions seen only on ultrasound.
Preliminary results from ASTOUND are extremely important in helping to inform personalized screening choices for women with dense breasts. Guidelines on these issues are planned, but often limit recommendations to those based on evidence from randomized trials with mortality as an end point. Our knowledge of the natural history of breast cancer and results from randomized trials of mammography should inform guidelines for supplemental screening.
Dr. Wendie A. Berg is at Magee-Womens Hospital of University of Pittsburgh Medical Center. She reported serving in a consulting or advisory role with SuperSonic Imagine. These comments were taken from her accompanying editorial (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.65.8674).
Currently, 24 American states have laws requiring that women receive some level of notification about breast density with their mammography results. Dense breast tissue can hide cancer on mammography, especially when the cancer lacks calcifications, resulting in delayed diagnosis and worse outcomes. Moreover, dense breast tissue is an independent risk factor for developing breast cancer.
Because the primary goal of screening is detection of early breast cancer, ultrasound would seem the clear choice, compared with tomosynthesis. Given comparable false-positive rates in ASTOUND, the estimated cost per cancer detected would be similar or more favorable for ultrasound than tomosynthesis. Ultrasound equipment is becoming much less expensive, requires no ionizing radiation, and it is easy to guide needle biopsy of lesions seen only on ultrasound.
Preliminary results from ASTOUND are extremely important in helping to inform personalized screening choices for women with dense breasts. Guidelines on these issues are planned, but often limit recommendations to those based on evidence from randomized trials with mortality as an end point. Our knowledge of the natural history of breast cancer and results from randomized trials of mammography should inform guidelines for supplemental screening.
Dr. Wendie A. Berg is at Magee-Womens Hospital of University of Pittsburgh Medical Center. She reported serving in a consulting or advisory role with SuperSonic Imagine. These comments were taken from her accompanying editorial (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.65.8674).
Currently, 24 American states have laws requiring that women receive some level of notification about breast density with their mammography results. Dense breast tissue can hide cancer on mammography, especially when the cancer lacks calcifications, resulting in delayed diagnosis and worse outcomes. Moreover, dense breast tissue is an independent risk factor for developing breast cancer.
Because the primary goal of screening is detection of early breast cancer, ultrasound would seem the clear choice, compared with tomosynthesis. Given comparable false-positive rates in ASTOUND, the estimated cost per cancer detected would be similar or more favorable for ultrasound than tomosynthesis. Ultrasound equipment is becoming much less expensive, requires no ionizing radiation, and it is easy to guide needle biopsy of lesions seen only on ultrasound.
Preliminary results from ASTOUND are extremely important in helping to inform personalized screening choices for women with dense breasts. Guidelines on these issues are planned, but often limit recommendations to those based on evidence from randomized trials with mortality as an end point. Our knowledge of the natural history of breast cancer and results from randomized trials of mammography should inform guidelines for supplemental screening.
Dr. Wendie A. Berg is at Magee-Womens Hospital of University of Pittsburgh Medical Center. She reported serving in a consulting or advisory role with SuperSonic Imagine. These comments were taken from her accompanying editorial (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.65.8674).
Ultrasound was about 1.8 times more sensitive than tomosynthesis for the incremental detection of breast cancer in women with radiologically dense breasts and negative two-dimensional mammography screening, according to interim results from the first prospective trial to directly compare the two modalities.
“However, future application of adjunct screening should consider that tomosynthesis detected more than 50% of the additional breast cancers in these women, and could potentially be [a] primary screening modality,” wrote Dr. Alberto Tagliafico of the University of Genoa (Italy) and his associates. The study was published online March 9 in the Journal of Clinical Oncology and presented simultaneously at the European Breast Cancer Conference.
Radiologically dense breast tissue undermines the sensitivity of mammography and is itself an independent risk factor for breast cancer. Recently, many states began requiring that women be informed of their breast density and adjunct screening measures, such as ultrasound. But estimates of the sensitivity of ultrasound have ranged from about 1.9 to 4.2 cancers for every 1,000 screens, said the researchers. This variance, combined with costs and concerns about false-positive recalls, have fueled debates about the value of adjunct measures in breast cancer screening, they added. To help clarify these issues, the multicenter ASTOUND (Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts) study compared physician-performed ultrasound and tomosynthesis results for 3,231 asymptomatic women aged 44 to 71 years, whose median age was 51 years (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.63.4147).
In all, the researchers detected 24 additional breast cancers, 23 of which were invasive. Thus, ultrasound detected about 7.1 additional cancers for every 1,000 screens (95% confidence interval, 4.2-10), compared with 4.0 additional cancers per 1,000 screens for tomosynthesis (95% CI, 1.8-6.2; P = .006). Only one cancer was detected by tomosynthesis alone. The rate of false-positive recalls was similar for the two modalities – 53 cases for tomosynthesis, versus 63 for ultrasound (P = .26). Rates of false-positive recalls leading to biopsy also were similar. Needle biopsies usually sufficed in recalled cases, but two women underwent surgical biopsies, both of which revealed radial scars.
If the final results of ASTOUND confirm these interim data, “it could be argued that breast tomosynthesis has little value in a setting where adjunct ultrasound is frequently used for screening women with mammography-dense breasts,” said the researchers. But tomosynthesis may have a role as a primary screening modality in other setting, especially because tomosynthesis acquisitions that also provide reconstructed 2D mammography are now available, lessening concerns about unjustified radiation exposure, they added.
The “modest” number of cancers in the interim report led to relatively wide confidence intervals, the investigators noted. Biomarker data were not available for all cancers, and both prevalent and incident ultrasound data were compared with prevalent tomosynthesis data, which might bias false-positive recall results in favor of ultrasound, they added.
Ultrasound was about 1.8 times more sensitive than tomosynthesis for the incremental detection of breast cancer in women with radiologically dense breasts and negative two-dimensional mammography screening, according to interim results from the first prospective trial to directly compare the two modalities.
“However, future application of adjunct screening should consider that tomosynthesis detected more than 50% of the additional breast cancers in these women, and could potentially be [a] primary screening modality,” wrote Dr. Alberto Tagliafico of the University of Genoa (Italy) and his associates. The study was published online March 9 in the Journal of Clinical Oncology and presented simultaneously at the European Breast Cancer Conference.
Radiologically dense breast tissue undermines the sensitivity of mammography and is itself an independent risk factor for breast cancer. Recently, many states began requiring that women be informed of their breast density and adjunct screening measures, such as ultrasound. But estimates of the sensitivity of ultrasound have ranged from about 1.9 to 4.2 cancers for every 1,000 screens, said the researchers. This variance, combined with costs and concerns about false-positive recalls, have fueled debates about the value of adjunct measures in breast cancer screening, they added. To help clarify these issues, the multicenter ASTOUND (Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts) study compared physician-performed ultrasound and tomosynthesis results for 3,231 asymptomatic women aged 44 to 71 years, whose median age was 51 years (J Clin Oncol. 2016 Mar 9. doi: 10.1200/JCO.2015.63.4147).
In all, the researchers detected 24 additional breast cancers, 23 of which were invasive. Thus, ultrasound detected about 7.1 additional cancers for every 1,000 screens (95% confidence interval, 4.2-10), compared with 4.0 additional cancers per 1,000 screens for tomosynthesis (95% CI, 1.8-6.2; P = .006). Only one cancer was detected by tomosynthesis alone. The rate of false-positive recalls was similar for the two modalities – 53 cases for tomosynthesis, versus 63 for ultrasound (P = .26). Rates of false-positive recalls leading to biopsy also were similar. Needle biopsies usually sufficed in recalled cases, but two women underwent surgical biopsies, both of which revealed radial scars.
If the final results of ASTOUND confirm these interim data, “it could be argued that breast tomosynthesis has little value in a setting where adjunct ultrasound is frequently used for screening women with mammography-dense breasts,” said the researchers. But tomosynthesis may have a role as a primary screening modality in other setting, especially because tomosynthesis acquisitions that also provide reconstructed 2D mammography are now available, lessening concerns about unjustified radiation exposure, they added.
The “modest” number of cancers in the interim report led to relatively wide confidence intervals, the investigators noted. Biomarker data were not available for all cancers, and both prevalent and incident ultrasound data were compared with prevalent tomosynthesis data, which might bias false-positive recall results in favor of ultrasound, they added.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Ultrasound outperformed tomosynthesis for the incremental detection of breast cancer in women with negative mammograms and radiologically dense breast tissue.
Major finding: Ultrasound detected about 7.1 additional cancers for every 1,000 screens (95% confidence interval, 4.2-10), compared with 4.0 additional cancers per 1,000 tomosynthesis screens (95% CI, 1.8-6.2; P = .006).
Data source: A multicenter, prospective trial comparing the two modalities in 3,231 women.
Disclosures: The University of Genoa sponsors the ASTOUND study. Dr. Tagliafico disclosed honoraria from Esaote-Philips, patents, royalties, or other intellectual property from Springer, and travel, accommodations, and expense support from Hologic and Technologic. Four coinvestigators reported financial relationships with several device and pharmaceutical companies. The senior author and the other seven coinvestigators had no disclosures.
High triglycerides linked to mortality in coronary heart disease
Severe hypertriglyceridemia significantly increased the long-term risk of death among patients with established coronary heart disease, even after accounting for low-density lipoprotein cholesterol, according to a large prospective study published March 8 in Circulation: Cardiovascular Quality and Outcomes.
“This effect is graded – the higher the triglycerides concentration, the higher the independent mortality risk,” said Dr. Robert Klempfner at Sheba Medical Center in Tel-Hashomer, Israel, and his associates. Thus, patients whose triglycerides measured at least 500 mg/dL were 68% more likely to die in the next 2 decades than were patients with triglycerides levels of than 100 mg/dL (P less than .001). The relative increase in risk was 29% for patients with levels between 200-499 mg/dL and 16% for those measuring between 150-200 mg/dL.
Prior studies of hypertriglyceridemia in patients with established congenital heart disease have been small, with short follow-up periods and inconclusive results, the investigators noted. Therefore, they analyzed national registry mortality data and fasting triglyceride levels for 15,355 patients who had been screened for the Bezafibrate Infarction Prevention trial during 1990 and 1992. They grouped patients as low-normal (less than 100 mg/dL); high-normal (100-149 mg/dL); borderline hypertriglyceridemia (150-199 mg/dL); moderate hypertriglyceridemia (200-499 mg/dL); and severe hypertriglyceridemia (at least 500 mg/dL; (Circ Cardiovasc Qual Outcomes. 2016 Mar 8. doi: 10.1161/CIRCOUTCOMES.115.002104).
After researchers adjusted for age and sex, the overall survival rate during 22 years of follow-up was 41% in the low-normal triglycerides group and 37%, 36%, 35%, and 25% in the higher triglycerides cohorts, respectively (P less than .001). In the adjusted model, each 1 unit natural logarithm increase in triglycerides corresponded with a 6% rise in the 22-year risk of all-cause mortality (P = .016).
Limited follow-up data after screening prevented the researchers from controlling for a variety of confounders, but the results nonetheless support consideration for lower triglyceride targets and highlight the need for prospective studies in “appropriately selected subjects,” they added.
The researchers reported no funding sources and had no disclosures.
Klempfner and his colleagues add further support for a role of triglycerides in promoting mortality, likely via an increase in cardiovascular disease mortality. This research takes on special importance given that elevations in triglycerides are increasingly common.
 |
Dr. Karol E. Watson |
Although we search for the true significance of elevated triglycerides in cardiovascular risk and potentially the optimal method to lower triglycerides, we congratulate the researchers on an important study, which provides support for the idea that triglycerides should be considered more seriously as a future target to improve our patients’ outcomes. Be reminded, however, that we currently do not know if triglyceride elevations will hold similar predictive value in patients whose low-density lipoprotein cholesterol is optimally controlled. And we must always remember that simply because something may or may not be a cardiovascular risk factor, altering it pharmacologically does not always mean that we will lower risk.
Dr. Karol E. Watson is at the University of California, Los Angeles. Dr. Philipp Wiesner is at the University of California, San Diego. These comments were taken from their editorial. They had no disclosures.
Klempfner and his colleagues add further support for a role of triglycerides in promoting mortality, likely via an increase in cardiovascular disease mortality. This research takes on special importance given that elevations in triglycerides are increasingly common.
|
Dr. Karol E. Watson |
Although we search for the true significance of elevated triglycerides in cardiovascular risk and potentially the optimal method to lower triglycerides, we congratulate the researchers on an important study, which provides support for the idea that triglycerides should be considered more seriously as a future target to improve our patients’ outcomes. Be reminded, however, that we currently do not know if triglyceride elevations will hold similar predictive value in patients whose low-density lipoprotein cholesterol is optimally controlled. And we must always remember that simply because something may or may not be a cardiovascular risk factor, altering it pharmacologically does not always mean that we will lower risk.
Dr. Karol E. Watson is at the University of California, Los Angeles. Dr. Philipp Wiesner is at the University of California, San Diego. These comments were taken from their editorial. They had no disclosures.
Klempfner and his colleagues add further support for a role of triglycerides in promoting mortality, likely via an increase in cardiovascular disease mortality. This research takes on special importance given that elevations in triglycerides are increasingly common.
|
Dr. Karol E. Watson |
Although we search for the true significance of elevated triglycerides in cardiovascular risk and potentially the optimal method to lower triglycerides, we congratulate the researchers on an important study, which provides support for the idea that triglycerides should be considered more seriously as a future target to improve our patients’ outcomes. Be reminded, however, that we currently do not know if triglyceride elevations will hold similar predictive value in patients whose low-density lipoprotein cholesterol is optimally controlled. And we must always remember that simply because something may or may not be a cardiovascular risk factor, altering it pharmacologically does not always mean that we will lower risk.
Dr. Karol E. Watson is at the University of California, Los Angeles. Dr. Philipp Wiesner is at the University of California, San Diego. These comments were taken from their editorial. They had no disclosures.
Severe hypertriglyceridemia significantly increased the long-term risk of death among patients with established coronary heart disease, even after accounting for low-density lipoprotein cholesterol, according to a large prospective study published March 8 in Circulation: Cardiovascular Quality and Outcomes.
“This effect is graded – the higher the triglycerides concentration, the higher the independent mortality risk,” said Dr. Robert Klempfner at Sheba Medical Center in Tel-Hashomer, Israel, and his associates. Thus, patients whose triglycerides measured at least 500 mg/dL were 68% more likely to die in the next 2 decades than were patients with triglycerides levels of than 100 mg/dL (P less than .001). The relative increase in risk was 29% for patients with levels between 200-499 mg/dL and 16% for those measuring between 150-200 mg/dL.
Prior studies of hypertriglyceridemia in patients with established congenital heart disease have been small, with short follow-up periods and inconclusive results, the investigators noted. Therefore, they analyzed national registry mortality data and fasting triglyceride levels for 15,355 patients who had been screened for the Bezafibrate Infarction Prevention trial during 1990 and 1992. They grouped patients as low-normal (less than 100 mg/dL); high-normal (100-149 mg/dL); borderline hypertriglyceridemia (150-199 mg/dL); moderate hypertriglyceridemia (200-499 mg/dL); and severe hypertriglyceridemia (at least 500 mg/dL; (Circ Cardiovasc Qual Outcomes. 2016 Mar 8. doi: 10.1161/CIRCOUTCOMES.115.002104).
After researchers adjusted for age and sex, the overall survival rate during 22 years of follow-up was 41% in the low-normal triglycerides group and 37%, 36%, 35%, and 25% in the higher triglycerides cohorts, respectively (P less than .001). In the adjusted model, each 1 unit natural logarithm increase in triglycerides corresponded with a 6% rise in the 22-year risk of all-cause mortality (P = .016).
Limited follow-up data after screening prevented the researchers from controlling for a variety of confounders, but the results nonetheless support consideration for lower triglyceride targets and highlight the need for prospective studies in “appropriately selected subjects,” they added.
The researchers reported no funding sources and had no disclosures.
Severe hypertriglyceridemia significantly increased the long-term risk of death among patients with established coronary heart disease, even after accounting for low-density lipoprotein cholesterol, according to a large prospective study published March 8 in Circulation: Cardiovascular Quality and Outcomes.
“This effect is graded – the higher the triglycerides concentration, the higher the independent mortality risk,” said Dr. Robert Klempfner at Sheba Medical Center in Tel-Hashomer, Israel, and his associates. Thus, patients whose triglycerides measured at least 500 mg/dL were 68% more likely to die in the next 2 decades than were patients with triglycerides levels of than 100 mg/dL (P less than .001). The relative increase in risk was 29% for patients with levels between 200-499 mg/dL and 16% for those measuring between 150-200 mg/dL.
Prior studies of hypertriglyceridemia in patients with established congenital heart disease have been small, with short follow-up periods and inconclusive results, the investigators noted. Therefore, they analyzed national registry mortality data and fasting triglyceride levels for 15,355 patients who had been screened for the Bezafibrate Infarction Prevention trial during 1990 and 1992. They grouped patients as low-normal (less than 100 mg/dL); high-normal (100-149 mg/dL); borderline hypertriglyceridemia (150-199 mg/dL); moderate hypertriglyceridemia (200-499 mg/dL); and severe hypertriglyceridemia (at least 500 mg/dL; (Circ Cardiovasc Qual Outcomes. 2016 Mar 8. doi: 10.1161/CIRCOUTCOMES.115.002104).
After researchers adjusted for age and sex, the overall survival rate during 22 years of follow-up was 41% in the low-normal triglycerides group and 37%, 36%, 35%, and 25% in the higher triglycerides cohorts, respectively (P less than .001). In the adjusted model, each 1 unit natural logarithm increase in triglycerides corresponded with a 6% rise in the 22-year risk of all-cause mortality (P = .016).
Limited follow-up data after screening prevented the researchers from controlling for a variety of confounders, but the results nonetheless support consideration for lower triglyceride targets and highlight the need for prospective studies in “appropriately selected subjects,” they added.
The researchers reported no funding sources and had no disclosures.
FROM CIRCULATION: CARDIOVASCULAR QUALITY AND OUTCOMES
Key clinical point: Hypertriglyceridemia significantly increased the risk of mortality among patients with coronary heart disease.
Major finding: Patients whose triglycerides measured at least 500 mg/dL were 68% more likely to die in the subsequent 22 years than were patients with triglycerides levels of than 100 mg/dL (P less than .001).
Data source: A prospective study of 15,355 patients who had been screened for the Bezafibrate Infarction Prevention trial between 1990 and 1992.
Disclosures: The researchers reported no funding sources and had no disclosures.
Poor Physical Fitness Upped Diabetes Risk Regardless of Weight
Young, out-of-shape men were about three times more likely than physically fit men to develop type 2 diabetes later in life, even if their body weight was normal, reported the authors of a large registry study.
“These findings suggest that interventions to improve aerobic and muscle fitness levels early in life could help reduce risk for type 2 diabetes mellitus in adulthood,” Dr. Casey Crump, at the Icahn School of Medicine at Mount Sinai, New York, and his associates wrote in a study published online March 7 in Annals of Internal Medicine.
Future longitudinal studies of physical fitness could help identify “windows of susceptibility” and the best preventive measures, the researchers added.
A sedentary lifestyle is known to increase the risk of type 2 diabetes, but less is known about how physical fitness affects risk.
To explore the question, the researchers identified 1,534,425 men without baseline diabetes who underwent military conscription physical examinations between 1969 and 1997. They tracked the men until up to 62 years of age by analyzing both the Swedish Hospital Registry and the Swedish Outpatient Registry (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M15-2002).
In all, 34,008 men developed type 2 diabetes over 39.4 million years of follow-up, the investigators said. Both low cardiorespiratory fitness and low muscle strength independently increased the risk for type 2 diabetes, regardless of whether the men had a high or normal body weight.
Moreover, the combination of low cardiorespiratory fitness and poor muscular fitness increased type 2 diabetes risk threefold (adjusted hazard ratio, 3.07; 95% confidence interval, 2.88 to 3.27; P less than .001), with a positive additive interaction (P less than .001).
Accounting for smoking lowered the associations between poor baseline fitness and type 2 diabetes by about 9%; but they remained significant (P less than .001), suggesting that unmeasured confounding “had little influence on our main findings,” the investigators said. If the associations are causal, then aerobic conditioning programs targeting men with low muscle strength might have the greatest public health impact, they added.
The U.S. National Institutes of Health, the Swedish Research Council, and Region Skåne/Lund University funded the study. The researchers had no disclosures.
Given the global increase in type 2 diabetes prevalence, there is a pressing need for intervention strategies that reduce the progression of the disease as well as the risk for related complications and premature death. The study by Dr. Crump and his colleagues fills an important research gap by demonstrating a strong inverse association between physical fitness at a young age and long-term risk for type 2 diabetes, independent of weight status. The enhancement of cardiorespiratory and muscular fitness through habitual physical activity in all persons should be recommended as a frontline therapy to address the public health burden of type 2 diabetes.
Peter T. Katzmarzyk, Ph.D., is at Pennington Biomedical Research Center in Baton Rouge, La. He had no disclosures. These comments were taken from his accompanying editorial (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M16-0269).
Given the global increase in type 2 diabetes prevalence, there is a pressing need for intervention strategies that reduce the progression of the disease as well as the risk for related complications and premature death. The study by Dr. Crump and his colleagues fills an important research gap by demonstrating a strong inverse association between physical fitness at a young age and long-term risk for type 2 diabetes, independent of weight status. The enhancement of cardiorespiratory and muscular fitness through habitual physical activity in all persons should be recommended as a frontline therapy to address the public health burden of type 2 diabetes.
Peter T. Katzmarzyk, Ph.D., is at Pennington Biomedical Research Center in Baton Rouge, La. He had no disclosures. These comments were taken from his accompanying editorial (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M16-0269).
Given the global increase in type 2 diabetes prevalence, there is a pressing need for intervention strategies that reduce the progression of the disease as well as the risk for related complications and premature death. The study by Dr. Crump and his colleagues fills an important research gap by demonstrating a strong inverse association between physical fitness at a young age and long-term risk for type 2 diabetes, independent of weight status. The enhancement of cardiorespiratory and muscular fitness through habitual physical activity in all persons should be recommended as a frontline therapy to address the public health burden of type 2 diabetes.
Peter T. Katzmarzyk, Ph.D., is at Pennington Biomedical Research Center in Baton Rouge, La. He had no disclosures. These comments were taken from his accompanying editorial (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M16-0269).
Young, out-of-shape men were about three times more likely than physically fit men to develop type 2 diabetes later in life, even if their body weight was normal, reported the authors of a large registry study.
“These findings suggest that interventions to improve aerobic and muscle fitness levels early in life could help reduce risk for type 2 diabetes mellitus in adulthood,” Dr. Casey Crump, at the Icahn School of Medicine at Mount Sinai, New York, and his associates wrote in a study published online March 7 in Annals of Internal Medicine.
Future longitudinal studies of physical fitness could help identify “windows of susceptibility” and the best preventive measures, the researchers added.
A sedentary lifestyle is known to increase the risk of type 2 diabetes, but less is known about how physical fitness affects risk.
To explore the question, the researchers identified 1,534,425 men without baseline diabetes who underwent military conscription physical examinations between 1969 and 1997. They tracked the men until up to 62 years of age by analyzing both the Swedish Hospital Registry and the Swedish Outpatient Registry (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M15-2002).
In all, 34,008 men developed type 2 diabetes over 39.4 million years of follow-up, the investigators said. Both low cardiorespiratory fitness and low muscle strength independently increased the risk for type 2 diabetes, regardless of whether the men had a high or normal body weight.
Moreover, the combination of low cardiorespiratory fitness and poor muscular fitness increased type 2 diabetes risk threefold (adjusted hazard ratio, 3.07; 95% confidence interval, 2.88 to 3.27; P less than .001), with a positive additive interaction (P less than .001).
Accounting for smoking lowered the associations between poor baseline fitness and type 2 diabetes by about 9%; but they remained significant (P less than .001), suggesting that unmeasured confounding “had little influence on our main findings,” the investigators said. If the associations are causal, then aerobic conditioning programs targeting men with low muscle strength might have the greatest public health impact, they added.
The U.S. National Institutes of Health, the Swedish Research Council, and Region Skåne/Lund University funded the study. The researchers had no disclosures.
Young, out-of-shape men were about three times more likely than physically fit men to develop type 2 diabetes later in life, even if their body weight was normal, reported the authors of a large registry study.
“These findings suggest that interventions to improve aerobic and muscle fitness levels early in life could help reduce risk for type 2 diabetes mellitus in adulthood,” Dr. Casey Crump, at the Icahn School of Medicine at Mount Sinai, New York, and his associates wrote in a study published online March 7 in Annals of Internal Medicine.
Future longitudinal studies of physical fitness could help identify “windows of susceptibility” and the best preventive measures, the researchers added.
A sedentary lifestyle is known to increase the risk of type 2 diabetes, but less is known about how physical fitness affects risk.
To explore the question, the researchers identified 1,534,425 men without baseline diabetes who underwent military conscription physical examinations between 1969 and 1997. They tracked the men until up to 62 years of age by analyzing both the Swedish Hospital Registry and the Swedish Outpatient Registry (Ann Intern Med. 2016 Mar 8; doi: 10.7326/M15-2002).
In all, 34,008 men developed type 2 diabetes over 39.4 million years of follow-up, the investigators said. Both low cardiorespiratory fitness and low muscle strength independently increased the risk for type 2 diabetes, regardless of whether the men had a high or normal body weight.
Moreover, the combination of low cardiorespiratory fitness and poor muscular fitness increased type 2 diabetes risk threefold (adjusted hazard ratio, 3.07; 95% confidence interval, 2.88 to 3.27; P less than .001), with a positive additive interaction (P less than .001).
Accounting for smoking lowered the associations between poor baseline fitness and type 2 diabetes by about 9%; but they remained significant (P less than .001), suggesting that unmeasured confounding “had little influence on our main findings,” the investigators said. If the associations are causal, then aerobic conditioning programs targeting men with low muscle strength might have the greatest public health impact, they added.
The U.S. National Institutes of Health, the Swedish Research Council, and Region Skåne/Lund University funded the study. The researchers had no disclosures.
FROM ANNALS OF INTERNAL MEDICINE
