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Prolonged monitoring found best for detecting AF after cryptogenic stroke
Extended monitoring of heart rhythm detected paroxysmal atrial fibrillation in patients who had previously had a "cryptogenic" stroke or transient ischemic attack at significantly higher rates than did conventional methods in two separate, randomized studies published June 26 in the New England Journal of Medicine.
Revealing the occult atrial fibrillation (AF) is critical because stroke survivors whose AF is unrecognized typically receive antiplatelet therapy for secondary prevention, which is inferior to the anticoagulation treatment given for clinically apparent AF, both groups of researchers said.
In one study, investigators used noninvasive ambulatory ECG monitoring to track heart rhythm for 30 days in 572 patients aged 52-96 years (mean age, 72 years) soon after they had an ischemic stroke or transient ischemic attack (TIA). Comprehensive evaluations, typically including the conventional 24-hour session of Holter monitoring, failed to identify any AF or other cause of the event, so it was classified as cryptogenic, said Dr. David J. Gladstone of the division of neurology, University of Toronto, and coleader of the University of Toronto Stroke Program, and his associates.
At 16 stroke centers across Canada, these patients were randomly assigned during a 3-year period to either the prolonged ECG monitoring intervention (287 patients) or to one additional round of 24-hour Holter monitoring (285 control subjects) in the hope of detecting occult AF. The extended ECG monitoring proved superior, detecting at least one episode of AF in 16.1% of patients, compared with only 3.2% in the control group. The extended monitoring also was superior at detecting continuous AF lasting from 2.5 minutes to many hours, which was found in 9.9% of the intervention group vs. only 2.5% of the control group, the investigators reported (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1311376]).
The prolonged monitoring "nearly doubled the proportion of patients who subsequently received anticoagulant therapy for secondary prevention of stroke – a finding we interpret as a clinically meaningful change in treatment that has the potential to avert recurrent strokes," Dr. Gladstone and his associates wrote.
"We think that the common practice of relying on 24-48 hours of monitoring for AF after a stroke or TIA of undetermined cause is insufficient and consider it an initial screen rather than a final test, especially given our finding that the yield of clinical follow-up alone as a means of detecting AF was negligible," they added.
In the other study, conventional follow-up was compared against heart rhythm monitoring using an insertable cardiac monitor (ICM) in 441 patients (mean age, 61.5 years) who recently had an ischemic stroke or TIA classified as cryptogenic. The ICM automatically detected and recorded AF, irrespective of heart rate or symptoms. Patients in the control group "underwent assessment at scheduled and unscheduled visits, with ECG monitoring performed at the discretion of the site investigator," said Dr. Tommaso Sanna of the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, and his associates.
At 6 months, AF was detected in 8.9% of the 221 participants randomly assigned to the study intervention, compared with only 1.4% of the 220 control subjects. At 12 months, the AF detection rates were 12.4% and 2.0%, respectively. This difference in detection was consistent across all subgroups of patients, regardless of age, sex, race/ethnicity, type of index event, presence or absence of patent foramen ovale, and CHADS score, Dr. Sanna and his colleagues said (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1313600])
As was observed in Dr. Gladstone’s study, the use of oral anticoagulants for secondary prevention more than doubled among patients who received an ICM. The benefit of the ICM strategy was clear: only 14 devices would need to be implanted to detect an episode of AF during 6 months of monitoring, only 10 devices to detect an episode of AF during 12 months of follow-up, and only 4 devices to detect an episode of AF during 36 months of follow-up, they noted.
The findings of both studies indicate that in current practice, a substantial number of patients labeled as having cryptogenic stroke or TIA actually have occult AF that goes undiagnosed and untreated.
Dr. Gladstone’s study was supported by the Canadian Stroke Network, the Heart and Stroke Foundation of Ontario, the Bastable-Potts Chair in Stroke, the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, the University of Toronto, the Brain Sciences Program at Sunnybrook Health Sciences Centre, the Sunnybrook Research Institute, the Sam Sobara family, and the University of Toronto Brill Chair in Neurology. Dr. Gladstone reported receiving support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; his associates reported ties to numerous industry sources. Dr. Sanna’s study was supported by Medtronic, maker of the ICM used in the study. Dr. Sanna reported other ties to Medtronic, and his associates reported ties to numerous industry sources.
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The results of these two studies indicate that "prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke," said Dr. Hooman Kamel.
"Most patients with cryptogenic stroke or TIA should undergo at least several weeks of rhythm monitoring. Relatively inexpensive external loop recorders, such as those used in the [Gladstone] trial, will probably be cost-effective; the value of more expensive implantable loop recorders is less clear," he noted.
Dr. Kamel is in the department of neurology and the Feil Family Brain and Mind Research Institute at Cornell University, New York. He had no related financial disclosures. These remarks were taken from his editorial accompanying the reports by Dr. Gladstone and Dr. Sanna (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMe1405046]).
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The results of these two studies indicate that "prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke," said Dr. Hooman Kamel.
"Most patients with cryptogenic stroke or TIA should undergo at least several weeks of rhythm monitoring. Relatively inexpensive external loop recorders, such as those used in the [Gladstone] trial, will probably be cost-effective; the value of more expensive implantable loop recorders is less clear," he noted.
Dr. Kamel is in the department of neurology and the Feil Family Brain and Mind Research Institute at Cornell University, New York. He had no related financial disclosures. These remarks were taken from his editorial accompanying the reports by Dr. Gladstone and Dr. Sanna (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMe1405046]).
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The results of these two studies indicate that "prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke," said Dr. Hooman Kamel.
"Most patients with cryptogenic stroke or TIA should undergo at least several weeks of rhythm monitoring. Relatively inexpensive external loop recorders, such as those used in the [Gladstone] trial, will probably be cost-effective; the value of more expensive implantable loop recorders is less clear," he noted.
Dr. Kamel is in the department of neurology and the Feil Family Brain and Mind Research Institute at Cornell University, New York. He had no related financial disclosures. These remarks were taken from his editorial accompanying the reports by Dr. Gladstone and Dr. Sanna (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMe1405046]).
Extended monitoring of heart rhythm detected paroxysmal atrial fibrillation in patients who had previously had a "cryptogenic" stroke or transient ischemic attack at significantly higher rates than did conventional methods in two separate, randomized studies published June 26 in the New England Journal of Medicine.
Revealing the occult atrial fibrillation (AF) is critical because stroke survivors whose AF is unrecognized typically receive antiplatelet therapy for secondary prevention, which is inferior to the anticoagulation treatment given for clinically apparent AF, both groups of researchers said.
In one study, investigators used noninvasive ambulatory ECG monitoring to track heart rhythm for 30 days in 572 patients aged 52-96 years (mean age, 72 years) soon after they had an ischemic stroke or transient ischemic attack (TIA). Comprehensive evaluations, typically including the conventional 24-hour session of Holter monitoring, failed to identify any AF or other cause of the event, so it was classified as cryptogenic, said Dr. David J. Gladstone of the division of neurology, University of Toronto, and coleader of the University of Toronto Stroke Program, and his associates.
At 16 stroke centers across Canada, these patients were randomly assigned during a 3-year period to either the prolonged ECG monitoring intervention (287 patients) or to one additional round of 24-hour Holter monitoring (285 control subjects) in the hope of detecting occult AF. The extended ECG monitoring proved superior, detecting at least one episode of AF in 16.1% of patients, compared with only 3.2% in the control group. The extended monitoring also was superior at detecting continuous AF lasting from 2.5 minutes to many hours, which was found in 9.9% of the intervention group vs. only 2.5% of the control group, the investigators reported (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1311376]).
The prolonged monitoring "nearly doubled the proportion of patients who subsequently received anticoagulant therapy for secondary prevention of stroke – a finding we interpret as a clinically meaningful change in treatment that has the potential to avert recurrent strokes," Dr. Gladstone and his associates wrote.
"We think that the common practice of relying on 24-48 hours of monitoring for AF after a stroke or TIA of undetermined cause is insufficient and consider it an initial screen rather than a final test, especially given our finding that the yield of clinical follow-up alone as a means of detecting AF was negligible," they added.
In the other study, conventional follow-up was compared against heart rhythm monitoring using an insertable cardiac monitor (ICM) in 441 patients (mean age, 61.5 years) who recently had an ischemic stroke or TIA classified as cryptogenic. The ICM automatically detected and recorded AF, irrespective of heart rate or symptoms. Patients in the control group "underwent assessment at scheduled and unscheduled visits, with ECG monitoring performed at the discretion of the site investigator," said Dr. Tommaso Sanna of the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, and his associates.
At 6 months, AF was detected in 8.9% of the 221 participants randomly assigned to the study intervention, compared with only 1.4% of the 220 control subjects. At 12 months, the AF detection rates were 12.4% and 2.0%, respectively. This difference in detection was consistent across all subgroups of patients, regardless of age, sex, race/ethnicity, type of index event, presence or absence of patent foramen ovale, and CHADS score, Dr. Sanna and his colleagues said (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1313600])
As was observed in Dr. Gladstone’s study, the use of oral anticoagulants for secondary prevention more than doubled among patients who received an ICM. The benefit of the ICM strategy was clear: only 14 devices would need to be implanted to detect an episode of AF during 6 months of monitoring, only 10 devices to detect an episode of AF during 12 months of follow-up, and only 4 devices to detect an episode of AF during 36 months of follow-up, they noted.
The findings of both studies indicate that in current practice, a substantial number of patients labeled as having cryptogenic stroke or TIA actually have occult AF that goes undiagnosed and untreated.
Dr. Gladstone’s study was supported by the Canadian Stroke Network, the Heart and Stroke Foundation of Ontario, the Bastable-Potts Chair in Stroke, the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, the University of Toronto, the Brain Sciences Program at Sunnybrook Health Sciences Centre, the Sunnybrook Research Institute, the Sam Sobara family, and the University of Toronto Brill Chair in Neurology. Dr. Gladstone reported receiving support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; his associates reported ties to numerous industry sources. Dr. Sanna’s study was supported by Medtronic, maker of the ICM used in the study. Dr. Sanna reported other ties to Medtronic, and his associates reported ties to numerous industry sources.
Extended monitoring of heart rhythm detected paroxysmal atrial fibrillation in patients who had previously had a "cryptogenic" stroke or transient ischemic attack at significantly higher rates than did conventional methods in two separate, randomized studies published June 26 in the New England Journal of Medicine.
Revealing the occult atrial fibrillation (AF) is critical because stroke survivors whose AF is unrecognized typically receive antiplatelet therapy for secondary prevention, which is inferior to the anticoagulation treatment given for clinically apparent AF, both groups of researchers said.
In one study, investigators used noninvasive ambulatory ECG monitoring to track heart rhythm for 30 days in 572 patients aged 52-96 years (mean age, 72 years) soon after they had an ischemic stroke or transient ischemic attack (TIA). Comprehensive evaluations, typically including the conventional 24-hour session of Holter monitoring, failed to identify any AF or other cause of the event, so it was classified as cryptogenic, said Dr. David J. Gladstone of the division of neurology, University of Toronto, and coleader of the University of Toronto Stroke Program, and his associates.
At 16 stroke centers across Canada, these patients were randomly assigned during a 3-year period to either the prolonged ECG monitoring intervention (287 patients) or to one additional round of 24-hour Holter monitoring (285 control subjects) in the hope of detecting occult AF. The extended ECG monitoring proved superior, detecting at least one episode of AF in 16.1% of patients, compared with only 3.2% in the control group. The extended monitoring also was superior at detecting continuous AF lasting from 2.5 minutes to many hours, which was found in 9.9% of the intervention group vs. only 2.5% of the control group, the investigators reported (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1311376]).
The prolonged monitoring "nearly doubled the proportion of patients who subsequently received anticoagulant therapy for secondary prevention of stroke – a finding we interpret as a clinically meaningful change in treatment that has the potential to avert recurrent strokes," Dr. Gladstone and his associates wrote.
"We think that the common practice of relying on 24-48 hours of monitoring for AF after a stroke or TIA of undetermined cause is insufficient and consider it an initial screen rather than a final test, especially given our finding that the yield of clinical follow-up alone as a means of detecting AF was negligible," they added.
In the other study, conventional follow-up was compared against heart rhythm monitoring using an insertable cardiac monitor (ICM) in 441 patients (mean age, 61.5 years) who recently had an ischemic stroke or TIA classified as cryptogenic. The ICM automatically detected and recorded AF, irrespective of heart rate or symptoms. Patients in the control group "underwent assessment at scheduled and unscheduled visits, with ECG monitoring performed at the discretion of the site investigator," said Dr. Tommaso Sanna of the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, and his associates.
At 6 months, AF was detected in 8.9% of the 221 participants randomly assigned to the study intervention, compared with only 1.4% of the 220 control subjects. At 12 months, the AF detection rates were 12.4% and 2.0%, respectively. This difference in detection was consistent across all subgroups of patients, regardless of age, sex, race/ethnicity, type of index event, presence or absence of patent foramen ovale, and CHADS score, Dr. Sanna and his colleagues said (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1313600])
As was observed in Dr. Gladstone’s study, the use of oral anticoagulants for secondary prevention more than doubled among patients who received an ICM. The benefit of the ICM strategy was clear: only 14 devices would need to be implanted to detect an episode of AF during 6 months of monitoring, only 10 devices to detect an episode of AF during 12 months of follow-up, and only 4 devices to detect an episode of AF during 36 months of follow-up, they noted.
The findings of both studies indicate that in current practice, a substantial number of patients labeled as having cryptogenic stroke or TIA actually have occult AF that goes undiagnosed and untreated.
Dr. Gladstone’s study was supported by the Canadian Stroke Network, the Heart and Stroke Foundation of Ontario, the Bastable-Potts Chair in Stroke, the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, the University of Toronto, the Brain Sciences Program at Sunnybrook Health Sciences Centre, the Sunnybrook Research Institute, the Sam Sobara family, and the University of Toronto Brill Chair in Neurology. Dr. Gladstone reported receiving support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; his associates reported ties to numerous industry sources. Dr. Sanna’s study was supported by Medtronic, maker of the ICM used in the study. Dr. Sanna reported other ties to Medtronic, and his associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: 24-hour Holter monitoring or conventional ECG monitoring is insufficient to detect AF in patients who had a cryptogenic stroke.
Major finding: Rates of AF detection were 16.1% for 30-day noninvasive ECG monitoring vs. 3.2% for controls, and 8.9% at 6 months for an insertable cardiac monitor vs. 1.4% for controls.
Data source: A randomized clinical trial comparing the detection of occult AF between 286 patients assigned to 30-day, noninvasive heart rhythm monitoring and 285 who received conventional care, and a randomized clinical trial comparing the detection of occult AF between 221 patients assigned to an insertable cardiac monitor and 220 who received conventional care.
Disclosures: Dr. Gladstone’s study was supported by various Canadian nonprofit foundations and institutes. He and his associates reported receiving financial support from numerous industry sources. Dr. Sanna’s study was supported by Medtronic. He reported other ties to Medtronic, and his associates reported ties to numerous industry sources.
Adding tomosynthesis improved mammography’s cancer detection
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
FROM JAMA
Key clinical point: Tomosynthesis may reduce the need for repeat imaging to detect breast cancer.
Major finding: The "recall" rate declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%; at the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%.
Data source: A retrospective multicenter analysis of screening digital mammography’s performance before (281,187 scans) and after (173,663 scans) the introduction of tomosynthesis to improve its accuracy.
Disclosures: This study was funded by Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic, which makes tomosynthesis equipment.
Women benefit from CRT at shorter QRS durations
Women with mild heart failure and left bundle branch block benefit from cardiac resynchronization therapy at a shorter QRS duration – less than 150 milliseconds – than do men, according to a report published online June 23 in JAMA Internal Medicine.
Current guidelines limit the class I indication for CRT to patients with mild heart failure, LBBB, and a QRS interval of 150 msec or longer. They are based on clinical trials in which women were underrepresented, comprising only about 20% of participants. Noting that QRS duration is generally shorter in women than in men, Food and Drug Administration researchers examined whether women might benefit from CRT at a shorter QRS duration than men do, said Dr. Robbert Zusterzeel and his associates at the FDA’s Center for Devices and Radiological Health.
They performed a pooled analysis of patient-level data from three large, randomized clinical trials submitted to the FDA as part of an application for premarketing approval of the CRT devices: 1,820 participants in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 1,663 from the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study, and 593 from the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.
In women overall, CRT produced a 60% relative reduction in the combined end point of heart failure event or death and a 55% relative reduction in death alone, compared with relative reductions of only 26% and 15% in men. In the subgroup of women who had QRS durations of 130-139 msec, CRT resulted in an 85% relative reduction in heart failure event or death; and in women with QRS durations of 140-149 msec, CRT resulted in a 69% relative reduction. In contrast, men with QRS durations in this low range did not benefit from CRT, Dr. Zusterzeel and his associates said (JAMA Intern. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.2717]).
"Considering that women receive CRT less often than men, we believe that the current findings are important to communicate" to clinicians and patients, they said.
Their study also "highlights the importance of sex-specific analysis in medical device clinical studies and the public health value of combining individual-patient data from clinical trials submitted to the FDA," the investigators added.
This study was supported in part by the FDA Office of Women’s Health, the Oak Ridge Institute for Science and Education, and the U.S. Department of Energy. No financial conflicts of interest were reported.
These new findings indicate that CRT is likely underused in women, who show greater benefit from the treatment than men do.
These results also shed light on a major contributor to the misdiagnosis and suboptimal treatment of CVD in women: Guidelines are typically based on a male standard and do not address important differences in women.
Women remain the minority of research subjects even though they are the majority of persons dying of CVD.
Dr. C. Noel Bairey Merz is at the Barbra Streisand Women’s Heart Center, Cedars Sinai Heart Institute, Los Angeles. Dr. Vera Regitz-Zagrosek is at the Institute for Gender in Medicine at Charité University and at the German Cardiovascular Research Center, both in Berlin. They reported no financial conflicts of interest. These remarks were taken from their commentary accompanying Dr. Zusterzeel’s report (JAMA Inter. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.320]). This work was supported by the National Institutes of Health, the National Center for Research Resources, the Gustavus and Louise Pfeiffer Research Foundation, the Women’s Guild of Cedars-Sinai Medical Center, and several others.
These new findings indicate that CRT is likely underused in women, who show greater benefit from the treatment than men do.
These results also shed light on a major contributor to the misdiagnosis and suboptimal treatment of CVD in women: Guidelines are typically based on a male standard and do not address important differences in women.
Women remain the minority of research subjects even though they are the majority of persons dying of CVD.
Dr. C. Noel Bairey Merz is at the Barbra Streisand Women’s Heart Center, Cedars Sinai Heart Institute, Los Angeles. Dr. Vera Regitz-Zagrosek is at the Institute for Gender in Medicine at Charité University and at the German Cardiovascular Research Center, both in Berlin. They reported no financial conflicts of interest. These remarks were taken from their commentary accompanying Dr. Zusterzeel’s report (JAMA Inter. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.320]). This work was supported by the National Institutes of Health, the National Center for Research Resources, the Gustavus and Louise Pfeiffer Research Foundation, the Women’s Guild of Cedars-Sinai Medical Center, and several others.
These new findings indicate that CRT is likely underused in women, who show greater benefit from the treatment than men do.
These results also shed light on a major contributor to the misdiagnosis and suboptimal treatment of CVD in women: Guidelines are typically based on a male standard and do not address important differences in women.
Women remain the minority of research subjects even though they are the majority of persons dying of CVD.
Dr. C. Noel Bairey Merz is at the Barbra Streisand Women’s Heart Center, Cedars Sinai Heart Institute, Los Angeles. Dr. Vera Regitz-Zagrosek is at the Institute for Gender in Medicine at Charité University and at the German Cardiovascular Research Center, both in Berlin. They reported no financial conflicts of interest. These remarks were taken from their commentary accompanying Dr. Zusterzeel’s report (JAMA Inter. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.320]). This work was supported by the National Institutes of Health, the National Center for Research Resources, the Gustavus and Louise Pfeiffer Research Foundation, the Women’s Guild of Cedars-Sinai Medical Center, and several others.
Women with mild heart failure and left bundle branch block benefit from cardiac resynchronization therapy at a shorter QRS duration – less than 150 milliseconds – than do men, according to a report published online June 23 in JAMA Internal Medicine.
Current guidelines limit the class I indication for CRT to patients with mild heart failure, LBBB, and a QRS interval of 150 msec or longer. They are based on clinical trials in which women were underrepresented, comprising only about 20% of participants. Noting that QRS duration is generally shorter in women than in men, Food and Drug Administration researchers examined whether women might benefit from CRT at a shorter QRS duration than men do, said Dr. Robbert Zusterzeel and his associates at the FDA’s Center for Devices and Radiological Health.
They performed a pooled analysis of patient-level data from three large, randomized clinical trials submitted to the FDA as part of an application for premarketing approval of the CRT devices: 1,820 participants in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 1,663 from the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study, and 593 from the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.
In women overall, CRT produced a 60% relative reduction in the combined end point of heart failure event or death and a 55% relative reduction in death alone, compared with relative reductions of only 26% and 15% in men. In the subgroup of women who had QRS durations of 130-139 msec, CRT resulted in an 85% relative reduction in heart failure event or death; and in women with QRS durations of 140-149 msec, CRT resulted in a 69% relative reduction. In contrast, men with QRS durations in this low range did not benefit from CRT, Dr. Zusterzeel and his associates said (JAMA Intern. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.2717]).
"Considering that women receive CRT less often than men, we believe that the current findings are important to communicate" to clinicians and patients, they said.
Their study also "highlights the importance of sex-specific analysis in medical device clinical studies and the public health value of combining individual-patient data from clinical trials submitted to the FDA," the investigators added.
This study was supported in part by the FDA Office of Women’s Health, the Oak Ridge Institute for Science and Education, and the U.S. Department of Energy. No financial conflicts of interest were reported.
Women with mild heart failure and left bundle branch block benefit from cardiac resynchronization therapy at a shorter QRS duration – less than 150 milliseconds – than do men, according to a report published online June 23 in JAMA Internal Medicine.
Current guidelines limit the class I indication for CRT to patients with mild heart failure, LBBB, and a QRS interval of 150 msec or longer. They are based on clinical trials in which women were underrepresented, comprising only about 20% of participants. Noting that QRS duration is generally shorter in women than in men, Food and Drug Administration researchers examined whether women might benefit from CRT at a shorter QRS duration than men do, said Dr. Robbert Zusterzeel and his associates at the FDA’s Center for Devices and Radiological Health.
They performed a pooled analysis of patient-level data from three large, randomized clinical trials submitted to the FDA as part of an application for premarketing approval of the CRT devices: 1,820 participants in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 1,663 from the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study, and 593 from the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.
In women overall, CRT produced a 60% relative reduction in the combined end point of heart failure event or death and a 55% relative reduction in death alone, compared with relative reductions of only 26% and 15% in men. In the subgroup of women who had QRS durations of 130-139 msec, CRT resulted in an 85% relative reduction in heart failure event or death; and in women with QRS durations of 140-149 msec, CRT resulted in a 69% relative reduction. In contrast, men with QRS durations in this low range did not benefit from CRT, Dr. Zusterzeel and his associates said (JAMA Intern. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.2717]).
"Considering that women receive CRT less often than men, we believe that the current findings are important to communicate" to clinicians and patients, they said.
Their study also "highlights the importance of sex-specific analysis in medical device clinical studies and the public health value of combining individual-patient data from clinical trials submitted to the FDA," the investigators added.
This study was supported in part by the FDA Office of Women’s Health, the Oak Ridge Institute for Science and Education, and the U.S. Department of Energy. No financial conflicts of interest were reported.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Women, especially those with QRS durations of 130-139 msec, benefit more from CRT therapy than men do.
Major finding: In women who had QRS durations of 130-139 msec, CRT produced an 85% relative reduction in heart failure event or death, and in women with QRS durations of 140-149 msec, CRT produced a 69% relative reduction; in contrast, men with QRS durations in this low range did not benefit from CRT.
Data source: A patient-level pooled analysis of data from three large randomized clinical trials involving 4,076 patients with mild heart failure and LBBB who received either CRT or an ICD were followed for up to 3 years.
Disclosures: This study was supported in part by the FDA Office of Women’s Health, the Oak Ridge Institute for Science and Education, and the U.S. Department of Energy. No financial conflicts of interest were reported.
Combined imaging differentiated benign, cancerous breast tumors
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
FROM CLINICAL CANCER RESEARCH
Key clinical point: A combination of imaging techniques, which simultaneously assesses several processes involved in cancer development, achieved high diagnostic accuracy in distinguishing breast cancers from benign lesions.
Major finding: Only one combination of imaging techniques – 18fluorodeoxyglucose PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing malignancies from benign lesions.
Data source: A prospective, single-center feasibility study involving different combinations of breast imaging techniques to assess the likelihood of malignancy in 76 consecutive women who had suspicious findings on mammography or ultrasonography.
Disclosures: This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Genetic marker for better colon cancer prognosis halved among African Americans
In colon cancers, the prevalence of microsatellite instability, a genetic biomarker of hypermutable colon cancers, is only half as high among African American patients as among white patients, according to a report published online June 24 in Public Library of Science One.
Microsatellite instability generally predicts a better outcome for patients, compared with same-staged colon cancers that don’t have it. This may be due to the generation of neoantigens and an associated attraction of immune cells that could limit tumor growth and metastasis. Thus, this discrepancy between African Americans and whites in the rate of microsatellite instability may contribute to the well-known racial disparity in mortality from the disease, said Dr. John M. Carethers of the University of Michigan, Ann Arbor.
To explore whether the rate of microsatellite instability in colon cancers differs by race, Dr. Carethers and his associates analyzed data from a population-based, case-control cohort that oversampled African Americans – the North Carolina Colon Cancer Study. They performed DNA extraction and microsatellite analysis on 503 stored samples of invasive adenocarcinomas from African American (45%) and white (55%) patients who had been diagnosed in 1996-2000. Overall, 11% of these tumors showed microsatellite instability.
The prevalence of microsatellite instability was 7% in tumors among black patients, compared with 14% in tumors among white patients (PLoS One 2014 June 24 [doi:10.1371/journal.pone.0100461]).
In this study, as in previous studies, most colon cancers that did not carry microsatellite instability were proximal. Accordingly, African American patients were more likely than were whites to have proximal rather than distal tumors. The reason for this difference in tumor location is not yet known, but the finding "has implications for the approach to colon cancer screening in this population," the researchers noted.
This study was funded in part by the National Cancer Institute. Dr. Carethers and his associates reported no financial conflicts of interest.
In colon cancers, the prevalence of microsatellite instability, a genetic biomarker of hypermutable colon cancers, is only half as high among African American patients as among white patients, according to a report published online June 24 in Public Library of Science One.
Microsatellite instability generally predicts a better outcome for patients, compared with same-staged colon cancers that don’t have it. This may be due to the generation of neoantigens and an associated attraction of immune cells that could limit tumor growth and metastasis. Thus, this discrepancy between African Americans and whites in the rate of microsatellite instability may contribute to the well-known racial disparity in mortality from the disease, said Dr. John M. Carethers of the University of Michigan, Ann Arbor.
To explore whether the rate of microsatellite instability in colon cancers differs by race, Dr. Carethers and his associates analyzed data from a population-based, case-control cohort that oversampled African Americans – the North Carolina Colon Cancer Study. They performed DNA extraction and microsatellite analysis on 503 stored samples of invasive adenocarcinomas from African American (45%) and white (55%) patients who had been diagnosed in 1996-2000. Overall, 11% of these tumors showed microsatellite instability.
The prevalence of microsatellite instability was 7% in tumors among black patients, compared with 14% in tumors among white patients (PLoS One 2014 June 24 [doi:10.1371/journal.pone.0100461]).
In this study, as in previous studies, most colon cancers that did not carry microsatellite instability were proximal. Accordingly, African American patients were more likely than were whites to have proximal rather than distal tumors. The reason for this difference in tumor location is not yet known, but the finding "has implications for the approach to colon cancer screening in this population," the researchers noted.
This study was funded in part by the National Cancer Institute. Dr. Carethers and his associates reported no financial conflicts of interest.
In colon cancers, the prevalence of microsatellite instability, a genetic biomarker of hypermutable colon cancers, is only half as high among African American patients as among white patients, according to a report published online June 24 in Public Library of Science One.
Microsatellite instability generally predicts a better outcome for patients, compared with same-staged colon cancers that don’t have it. This may be due to the generation of neoantigens and an associated attraction of immune cells that could limit tumor growth and metastasis. Thus, this discrepancy between African Americans and whites in the rate of microsatellite instability may contribute to the well-known racial disparity in mortality from the disease, said Dr. John M. Carethers of the University of Michigan, Ann Arbor.
To explore whether the rate of microsatellite instability in colon cancers differs by race, Dr. Carethers and his associates analyzed data from a population-based, case-control cohort that oversampled African Americans – the North Carolina Colon Cancer Study. They performed DNA extraction and microsatellite analysis on 503 stored samples of invasive adenocarcinomas from African American (45%) and white (55%) patients who had been diagnosed in 1996-2000. Overall, 11% of these tumors showed microsatellite instability.
The prevalence of microsatellite instability was 7% in tumors among black patients, compared with 14% in tumors among white patients (PLoS One 2014 June 24 [doi:10.1371/journal.pone.0100461]).
In this study, as in previous studies, most colon cancers that did not carry microsatellite instability were proximal. Accordingly, African American patients were more likely than were whites to have proximal rather than distal tumors. The reason for this difference in tumor location is not yet known, but the finding "has implications for the approach to colon cancer screening in this population," the researchers noted.
This study was funded in part by the National Cancer Institute. Dr. Carethers and his associates reported no financial conflicts of interest.
FROM PUBLIC LIBRARY OF SCIENCE ONE
Key clinical point: Racial disparity in colon cancer mortality may be due in part to biological differences in tumor type.
Major finding: The prevalence of microsatellite instability in colon cancer samples was 7% among African American patients, compared with 14% among white patients.
Data source: A secondary analysis of data from the North Carolina Colon Cancer Study involving tumor samples from 227 African American and 276 white patients.
Disclosures: This study was funded in part by the National Cancer Institute. Dr. Carethers and his associates reported no financial conflicts of interest.
Tofacitinib bests methotrexate for RA
Tofacitinib was superior to methotrexate at reducing the signs and symptoms of rheumatoid arthritis, improving physical function, and slowing the progression of joint damage in a 2-year, phase III clinical trial sponsored by Pfizer.
The results of the study indicate that tofacitinib "can be more effective clinically, functionally, and radiographically than methotrexate in patients with rheumatoid arthritis who have not previously received methotrexate," Dr. Eun-Bong Lee of Seoul (South Korea) National University and his associates reported June 19 in the New England Journal of Medicine.
While nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate have been shown to be superior to methotrexate alone, other studies have not shown superiority of a biologic DMARD alone vs. methotrexate at times extending to 1 year or longer, they noted.
Tofacitinib (Xeljanz), a targeted, small-molecule Janus kinase inhibitor, was approved by the Food and Drug Administration in November 2012 for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate.
In the trial conducted at 151 medical centers worldwide, 956 adults with active, moderate to severe RA who had never received methotrexate or tofacitinib were randomly assigned to receive 5 mg of oral tofacitinib twice daily (373 patients), 10 mg of oral tofacitinib twice daily (397 patients), or methotrexate (186 patients) for 2 years. The mean duration of RA at entry into the study was approximately 3 years, the investigators wrote.
At 6, 12, and 24 months, there was no decline in van der Heijde modified total Sharp score (a radiographic measure of structural joint damage), as well as on measures of joint erosion and joint-space narrowing, in a significantly greater proportion of patients who were taking tofacitinib than in those who were taking methotrexate. In addition, 25.5% of the patients taking 5 mg of tofacitinib and 37.7% of those taking 10 mg of tofacitinib achieved an American College of Rheumatology (ACR) 70 response (at least a 70% reduction in the number of tender and swollen joints plus equivalent improvement in three to five ACR core measures), compared with only 12.0% of patients in the methotrexate group.
Rates of remission and of low disease activity at 6, 12, and 24 months also were significantly higher in the two tofacitinib groups than in the methotrexate group, the investigators reported (N. Engl. J. Med. 2014;370:2377-86).
However, "the benefits of tofacitinib need to be considered in the context of the risks of adverse events," the authors wrote. As expected, the drug was associated with declines in neutrophil and lymphocyte counts, and with increases in lipid, aminotransferase, and creatinine levels. Herpes zoster infections developed in 4% of the two tofacitinib groups, compared with only 1.1% of the methotrexate group. *Five confirmed cases of cancer (non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, Burkitt’s B-cell lymphoma, and colon cancer) and one case of adrenal adenoma with unknown malignancy status developed in the tofacitinib group, compared with one confirmed case of cancer (gastric) in the methotrexate group.
This study was funded by Pfizer, which also collected and analyzed the data and assisted with writing the report. Dr. Lee reported receiving consulting fees from Pfizer; Dr. Lee’s associates reported ties to numerous industry sources.
*Correction, 7/1/2014: An earlier version of this story misstated the total number of confirmed cancers in the tofacitinib groups.
Tofacitinib was superior to methotrexate at reducing the signs and symptoms of rheumatoid arthritis, improving physical function, and slowing the progression of joint damage in a 2-year, phase III clinical trial sponsored by Pfizer.
The results of the study indicate that tofacitinib "can be more effective clinically, functionally, and radiographically than methotrexate in patients with rheumatoid arthritis who have not previously received methotrexate," Dr. Eun-Bong Lee of Seoul (South Korea) National University and his associates reported June 19 in the New England Journal of Medicine.
While nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate have been shown to be superior to methotrexate alone, other studies have not shown superiority of a biologic DMARD alone vs. methotrexate at times extending to 1 year or longer, they noted.
Tofacitinib (Xeljanz), a targeted, small-molecule Janus kinase inhibitor, was approved by the Food and Drug Administration in November 2012 for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate.
In the trial conducted at 151 medical centers worldwide, 956 adults with active, moderate to severe RA who had never received methotrexate or tofacitinib were randomly assigned to receive 5 mg of oral tofacitinib twice daily (373 patients), 10 mg of oral tofacitinib twice daily (397 patients), or methotrexate (186 patients) for 2 years. The mean duration of RA at entry into the study was approximately 3 years, the investigators wrote.
At 6, 12, and 24 months, there was no decline in van der Heijde modified total Sharp score (a radiographic measure of structural joint damage), as well as on measures of joint erosion and joint-space narrowing, in a significantly greater proportion of patients who were taking tofacitinib than in those who were taking methotrexate. In addition, 25.5% of the patients taking 5 mg of tofacitinib and 37.7% of those taking 10 mg of tofacitinib achieved an American College of Rheumatology (ACR) 70 response (at least a 70% reduction in the number of tender and swollen joints plus equivalent improvement in three to five ACR core measures), compared with only 12.0% of patients in the methotrexate group.
Rates of remission and of low disease activity at 6, 12, and 24 months also were significantly higher in the two tofacitinib groups than in the methotrexate group, the investigators reported (N. Engl. J. Med. 2014;370:2377-86).
However, "the benefits of tofacitinib need to be considered in the context of the risks of adverse events," the authors wrote. As expected, the drug was associated with declines in neutrophil and lymphocyte counts, and with increases in lipid, aminotransferase, and creatinine levels. Herpes zoster infections developed in 4% of the two tofacitinib groups, compared with only 1.1% of the methotrexate group. *Five confirmed cases of cancer (non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, Burkitt’s B-cell lymphoma, and colon cancer) and one case of adrenal adenoma with unknown malignancy status developed in the tofacitinib group, compared with one confirmed case of cancer (gastric) in the methotrexate group.
This study was funded by Pfizer, which also collected and analyzed the data and assisted with writing the report. Dr. Lee reported receiving consulting fees from Pfizer; Dr. Lee’s associates reported ties to numerous industry sources.
*Correction, 7/1/2014: An earlier version of this story misstated the total number of confirmed cancers in the tofacitinib groups.
Tofacitinib was superior to methotrexate at reducing the signs and symptoms of rheumatoid arthritis, improving physical function, and slowing the progression of joint damage in a 2-year, phase III clinical trial sponsored by Pfizer.
The results of the study indicate that tofacitinib "can be more effective clinically, functionally, and radiographically than methotrexate in patients with rheumatoid arthritis who have not previously received methotrexate," Dr. Eun-Bong Lee of Seoul (South Korea) National University and his associates reported June 19 in the New England Journal of Medicine.
While nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate have been shown to be superior to methotrexate alone, other studies have not shown superiority of a biologic DMARD alone vs. methotrexate at times extending to 1 year or longer, they noted.
Tofacitinib (Xeljanz), a targeted, small-molecule Janus kinase inhibitor, was approved by the Food and Drug Administration in November 2012 for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate.
In the trial conducted at 151 medical centers worldwide, 956 adults with active, moderate to severe RA who had never received methotrexate or tofacitinib were randomly assigned to receive 5 mg of oral tofacitinib twice daily (373 patients), 10 mg of oral tofacitinib twice daily (397 patients), or methotrexate (186 patients) for 2 years. The mean duration of RA at entry into the study was approximately 3 years, the investigators wrote.
At 6, 12, and 24 months, there was no decline in van der Heijde modified total Sharp score (a radiographic measure of structural joint damage), as well as on measures of joint erosion and joint-space narrowing, in a significantly greater proportion of patients who were taking tofacitinib than in those who were taking methotrexate. In addition, 25.5% of the patients taking 5 mg of tofacitinib and 37.7% of those taking 10 mg of tofacitinib achieved an American College of Rheumatology (ACR) 70 response (at least a 70% reduction in the number of tender and swollen joints plus equivalent improvement in three to five ACR core measures), compared with only 12.0% of patients in the methotrexate group.
Rates of remission and of low disease activity at 6, 12, and 24 months also were significantly higher in the two tofacitinib groups than in the methotrexate group, the investigators reported (N. Engl. J. Med. 2014;370:2377-86).
However, "the benefits of tofacitinib need to be considered in the context of the risks of adverse events," the authors wrote. As expected, the drug was associated with declines in neutrophil and lymphocyte counts, and with increases in lipid, aminotransferase, and creatinine levels. Herpes zoster infections developed in 4% of the two tofacitinib groups, compared with only 1.1% of the methotrexate group. *Five confirmed cases of cancer (non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, Burkitt’s B-cell lymphoma, and colon cancer) and one case of adrenal adenoma with unknown malignancy status developed in the tofacitinib group, compared with one confirmed case of cancer (gastric) in the methotrexate group.
This study was funded by Pfizer, which also collected and analyzed the data and assisted with writing the report. Dr. Lee reported receiving consulting fees from Pfizer; Dr. Lee’s associates reported ties to numerous industry sources.
*Correction, 7/1/2014: An earlier version of this story misstated the total number of confirmed cancers in the tofacitinib groups.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Tofacitinib monotherapy provided better outcomes at 2 years than did methotrexate alone in patients who previously had not been treated with either drug.
Major finding: 25.5% of the patients taking 5 mg of tofacitinib twice daily and 37.7% of those taking 10 mg of tofacitinib twice daily achieved an ACR 70 response, compared with only 12.0% of patients in the methotrexate group.
Data source: An international, randomized, double-blind phase III trial performed at 151 medical centers involving 956 adults with active RA who were treated with either tofacitinib or methotrexate for 2 years.
Disclosures: This study was funded by Pfizer, which also collected and analyzed the data and assisted with writing the report. Dr. Lee reported receiving consulting fees from Pfizer.
Maternal antidepressants don’t increase infant cardiac malformations
Infants born to women who took antidepressants during the first trimester of their pregnancies showed no increase in cardiac malformations overall or in specific cardiac defects that earlier research had linked to fetal exposure to the drugs, investigators have reported.
Previously, paroxetine and sertraline had been associated with congenital cardiac malformations, chiefly septal defects, but "considerable controversy" remains on the subject, the researchers noted in a report published online June 19 in the New England Journal of Medicine.
In the current large, population-based cohort study, the investigators drew from Medicaid records for 46 states and the District of Columbia and identified 949,504 completed pregnancies during a 7-year period. A total of 64,389 of these women (6.8%) used an antidepressant during their first trimester, including SSRIs, tricyclics, serotonin–norepinephrine reuptake inhibitors (SNRIs), and bupropion.
The SSRIs taken by women most frequently were sertraline, paroxetine, and fluoxetine, wrote Krista F. Huybrechts, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.
In the study’s initial analysis, cardiac malformations were diagnosed in 6,403 infants not exposed to antidepressants, for a rate of 72.3 malformations per 10,000 infants, and in 580 infants exposed to antidepressants, for a rate of 90.1 malformations per 10,000 infants. Once these data were adjusted to account for the effect of the underlying depression (indication bias), however, there was no association between the use of antidepressants in general and infant cardiac malformations, nor between specific antidepressants and specific cardiac malformations.
In particular, "we found no significant associations between paroxetine and right ventricular outflow tract obstruction or between sertraline and ventricular septal defect," Dr. Huybrechts and her associates said (N. Engl. J. Med. 2014 June 19 [doi:10.1056/NEJMoa1312828]).
In addition, numerous subgroup and sensitivity analyses found no such associations regardless of the women’s age, race, or use of monotherapy vs. polytherapy, and no dose-response relationships. In contrast, the data confirmed well-known associations between infant cardiac malformations and maternal diabetes, maternal use of anticonvulsants, and multiple gestations, which supports the premise that "the outcomes of interest were well captured in our study," the investigators said.
This study was supported by the Agency for Healthcare Research and Quality, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. Dr. Huybrechts reported no financial conflicts of interest; her associates reported numerous ties to industry sources.
Infants born to women who took antidepressants during the first trimester of their pregnancies showed no increase in cardiac malformations overall or in specific cardiac defects that earlier research had linked to fetal exposure to the drugs, investigators have reported.
Previously, paroxetine and sertraline had been associated with congenital cardiac malformations, chiefly septal defects, but "considerable controversy" remains on the subject, the researchers noted in a report published online June 19 in the New England Journal of Medicine.
In the current large, population-based cohort study, the investigators drew from Medicaid records for 46 states and the District of Columbia and identified 949,504 completed pregnancies during a 7-year period. A total of 64,389 of these women (6.8%) used an antidepressant during their first trimester, including SSRIs, tricyclics, serotonin–norepinephrine reuptake inhibitors (SNRIs), and bupropion.
The SSRIs taken by women most frequently were sertraline, paroxetine, and fluoxetine, wrote Krista F. Huybrechts, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.
In the study’s initial analysis, cardiac malformations were diagnosed in 6,403 infants not exposed to antidepressants, for a rate of 72.3 malformations per 10,000 infants, and in 580 infants exposed to antidepressants, for a rate of 90.1 malformations per 10,000 infants. Once these data were adjusted to account for the effect of the underlying depression (indication bias), however, there was no association between the use of antidepressants in general and infant cardiac malformations, nor between specific antidepressants and specific cardiac malformations.
In particular, "we found no significant associations between paroxetine and right ventricular outflow tract obstruction or between sertraline and ventricular septal defect," Dr. Huybrechts and her associates said (N. Engl. J. Med. 2014 June 19 [doi:10.1056/NEJMoa1312828]).
In addition, numerous subgroup and sensitivity analyses found no such associations regardless of the women’s age, race, or use of monotherapy vs. polytherapy, and no dose-response relationships. In contrast, the data confirmed well-known associations between infant cardiac malformations and maternal diabetes, maternal use of anticonvulsants, and multiple gestations, which supports the premise that "the outcomes of interest were well captured in our study," the investigators said.
This study was supported by the Agency for Healthcare Research and Quality, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. Dr. Huybrechts reported no financial conflicts of interest; her associates reported numerous ties to industry sources.
Infants born to women who took antidepressants during the first trimester of their pregnancies showed no increase in cardiac malformations overall or in specific cardiac defects that earlier research had linked to fetal exposure to the drugs, investigators have reported.
Previously, paroxetine and sertraline had been associated with congenital cardiac malformations, chiefly septal defects, but "considerable controversy" remains on the subject, the researchers noted in a report published online June 19 in the New England Journal of Medicine.
In the current large, population-based cohort study, the investigators drew from Medicaid records for 46 states and the District of Columbia and identified 949,504 completed pregnancies during a 7-year period. A total of 64,389 of these women (6.8%) used an antidepressant during their first trimester, including SSRIs, tricyclics, serotonin–norepinephrine reuptake inhibitors (SNRIs), and bupropion.
The SSRIs taken by women most frequently were sertraline, paroxetine, and fluoxetine, wrote Krista F. Huybrechts, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her associates.
In the study’s initial analysis, cardiac malformations were diagnosed in 6,403 infants not exposed to antidepressants, for a rate of 72.3 malformations per 10,000 infants, and in 580 infants exposed to antidepressants, for a rate of 90.1 malformations per 10,000 infants. Once these data were adjusted to account for the effect of the underlying depression (indication bias), however, there was no association between the use of antidepressants in general and infant cardiac malformations, nor between specific antidepressants and specific cardiac malformations.
In particular, "we found no significant associations between paroxetine and right ventricular outflow tract obstruction or between sertraline and ventricular septal defect," Dr. Huybrechts and her associates said (N. Engl. J. Med. 2014 June 19 [doi:10.1056/NEJMoa1312828]).
In addition, numerous subgroup and sensitivity analyses found no such associations regardless of the women’s age, race, or use of monotherapy vs. polytherapy, and no dose-response relationships. In contrast, the data confirmed well-known associations between infant cardiac malformations and maternal diabetes, maternal use of anticonvulsants, and multiple gestations, which supports the premise that "the outcomes of interest were well captured in our study," the investigators said.
This study was supported by the Agency for Healthcare Research and Quality, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. Dr. Huybrechts reported no financial conflicts of interest; her associates reported numerous ties to industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: First trimester use of antidepressants does not significantly increase fetal cardiac malformation risk.
Major finding: After adjustment, there was no association between the use of antidepressants in general and infant cardiac malformations, nor between specific antidepressants and specific cardiac malformations.
Data source: A nationwide cohort study involving 949,504 pregnancies in which 6.8% of the women took antidepressants during the first trimester.
Disclosures: This study was supported by the Agency for Healthcare Research and Quality, the National Institute of Mental Health, and the National Institute of Child Health and Human Development. Dr. Huybrechts reported no financial conflicts of interest; her associates reported numerous ties to industry sources.
Thrombolysis may offer benefit in stable pulmonary embolism
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
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Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE," said Dr. Joshua A. Beckman.
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported being a board member for Vascular Interventional Advances; receiving grant funding from Bristol-Myers Squibb; and consulting for AstraZeneca, Boston Scientific, Ferring, Merck, and Novartis. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
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Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE," said Dr. Joshua A. Beckman.
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported being a board member for Vascular Interventional Advances; receiving grant funding from Bristol-Myers Squibb; and consulting for AstraZeneca, Boston Scientific, Ferring, Merck, and Novartis. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
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Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE," said Dr. Joshua A. Beckman.
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported being a board member for Vascular Interventional Advances; receiving grant funding from Bristol-Myers Squibb; and consulting for AstraZeneca, Boston Scientific, Ferring, Merck, and Novartis. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
FROM JAMA
Key clinical point: Thrombolysis may be a therapeutic alternative to anticoagulation in some patients with stable, intermediate-risk pulmonary embolism.
Major finding: Mortality was 2.17% in PE patients who received thrombolysis, compared with 3.89% in those who received anticoagulation; the risk of recurrent PE also was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
Data source: A meta-analysis of 16 randomized, controlled trials involving 2,115 patients with PE, including 1,499 with intermediate-risk PE, who were followed for a mean of 82 days.
Disclosures: Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
TNF-alpha antagonists did not increase cancer risk in IBD
The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.
At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.
They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.
A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).
There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.
"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.
The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.
The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.
At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.
They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.
A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).
There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.
"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.
The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.
The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.
At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.
They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.
A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).
There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.
"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.
The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.
FROM JAMA
Major finding: A total of 6.7% of patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with these agents.
Data source: A nationwide prospective cohort study involving 56,146 IBD patients aged 15 and older, of whom 4,553 took TNF-alpha antagonists, who were followed for approximately 10 years for the development of cancer.
Disclosures: The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.
Disability rates from blast-related, nonblast TBI similar
The adverse effects of concussive traumatic brain injury are similar whether the injury was sustained in a blast-related incident such as a bomb or improvised explosive device detonation or a nonblast incident such as a fall or car crash, a report published online June 16 in JAMA Neurology shows.
Researchers studied this issue by prospectively assessing the clinical outcomes of the two types of traumatic brain injury (TBI) in 178 patients injured while serving in Iraq and Afghanistan during a 3-year period. Study participants were enrolled immediately after evacuation from combat theaters, when they were medically assessed at Landstuhl Regional Medical Center in Germany, and were followed up at 6 and 12 months afterward, said Christine L. MacDonald, Ph.D., of the department of neurology, Washington University, St. Louis, and her associates.
A total of 53 patients sustained blast-plus-impact TBI; 29 sustained nonblast TBI from falls, crashes, or being struck in the head by a blunt object; and 96 who had no head injuries served as control subjects. In the control group, 27 had been exposed to blasts, and 69 had not been exposed to blasts; most required medical evaluation for gastrointestinal, dermatologic, gynecologic, or orthopedic indications.
Global outcomes as measured by the Glasgow Outcome Scale-Extended were "essentially indistinguishable" between blast-related and nonblast TBI, as were numerous neuropsychological abnormalities; neurobehavioral impairments; focal neurological deficits such as those affecting olfaction, gait, and limb ataxia; headache-related disability; PTSD and its components; depression; alcohol misuse; and sleep disturbances. This suggests that TBI itself, independent of the mechanism of injury and of the intensity of combat exposure, is the primary driver of adverse outcomes, Dr. MacDonald and her colleagues said (JAMA Neurol. 2014 June 16 [doi:10.1001/jamaneurol.2014.1114]).
Another important finding was that control subjects who had been exposed to blasts showed significantly worse outcomes than controls who had not been exposed to blasts on measures of neurobehavioral, psychiatric, and headache-related impairment. It is possible that subconcussive blast exposure might cause direct structural damage to the brain or that other factors associated with blast exposure might play a role, the investigators added.
The relatively modest sample size and potential selection bias were cited by Dr. MacDonald and her associates as possible study limitations.
This study was funded by the Congressionally Directed Medical Research Programs. Dr. MacDonald and her associates reported no financial conflicts of interest.
The adverse effects of concussive traumatic brain injury are similar whether the injury was sustained in a blast-related incident such as a bomb or improvised explosive device detonation or a nonblast incident such as a fall or car crash, a report published online June 16 in JAMA Neurology shows.
Researchers studied this issue by prospectively assessing the clinical outcomes of the two types of traumatic brain injury (TBI) in 178 patients injured while serving in Iraq and Afghanistan during a 3-year period. Study participants were enrolled immediately after evacuation from combat theaters, when they were medically assessed at Landstuhl Regional Medical Center in Germany, and were followed up at 6 and 12 months afterward, said Christine L. MacDonald, Ph.D., of the department of neurology, Washington University, St. Louis, and her associates.
A total of 53 patients sustained blast-plus-impact TBI; 29 sustained nonblast TBI from falls, crashes, or being struck in the head by a blunt object; and 96 who had no head injuries served as control subjects. In the control group, 27 had been exposed to blasts, and 69 had not been exposed to blasts; most required medical evaluation for gastrointestinal, dermatologic, gynecologic, or orthopedic indications.
Global outcomes as measured by the Glasgow Outcome Scale-Extended were "essentially indistinguishable" between blast-related and nonblast TBI, as were numerous neuropsychological abnormalities; neurobehavioral impairments; focal neurological deficits such as those affecting olfaction, gait, and limb ataxia; headache-related disability; PTSD and its components; depression; alcohol misuse; and sleep disturbances. This suggests that TBI itself, independent of the mechanism of injury and of the intensity of combat exposure, is the primary driver of adverse outcomes, Dr. MacDonald and her colleagues said (JAMA Neurol. 2014 June 16 [doi:10.1001/jamaneurol.2014.1114]).
Another important finding was that control subjects who had been exposed to blasts showed significantly worse outcomes than controls who had not been exposed to blasts on measures of neurobehavioral, psychiatric, and headache-related impairment. It is possible that subconcussive blast exposure might cause direct structural damage to the brain or that other factors associated with blast exposure might play a role, the investigators added.
The relatively modest sample size and potential selection bias were cited by Dr. MacDonald and her associates as possible study limitations.
This study was funded by the Congressionally Directed Medical Research Programs. Dr. MacDonald and her associates reported no financial conflicts of interest.
The adverse effects of concussive traumatic brain injury are similar whether the injury was sustained in a blast-related incident such as a bomb or improvised explosive device detonation or a nonblast incident such as a fall or car crash, a report published online June 16 in JAMA Neurology shows.
Researchers studied this issue by prospectively assessing the clinical outcomes of the two types of traumatic brain injury (TBI) in 178 patients injured while serving in Iraq and Afghanistan during a 3-year period. Study participants were enrolled immediately after evacuation from combat theaters, when they were medically assessed at Landstuhl Regional Medical Center in Germany, and were followed up at 6 and 12 months afterward, said Christine L. MacDonald, Ph.D., of the department of neurology, Washington University, St. Louis, and her associates.
A total of 53 patients sustained blast-plus-impact TBI; 29 sustained nonblast TBI from falls, crashes, or being struck in the head by a blunt object; and 96 who had no head injuries served as control subjects. In the control group, 27 had been exposed to blasts, and 69 had not been exposed to blasts; most required medical evaluation for gastrointestinal, dermatologic, gynecologic, or orthopedic indications.
Global outcomes as measured by the Glasgow Outcome Scale-Extended were "essentially indistinguishable" between blast-related and nonblast TBI, as were numerous neuropsychological abnormalities; neurobehavioral impairments; focal neurological deficits such as those affecting olfaction, gait, and limb ataxia; headache-related disability; PTSD and its components; depression; alcohol misuse; and sleep disturbances. This suggests that TBI itself, independent of the mechanism of injury and of the intensity of combat exposure, is the primary driver of adverse outcomes, Dr. MacDonald and her colleagues said (JAMA Neurol. 2014 June 16 [doi:10.1001/jamaneurol.2014.1114]).
Another important finding was that control subjects who had been exposed to blasts showed significantly worse outcomes than controls who had not been exposed to blasts on measures of neurobehavioral, psychiatric, and headache-related impairment. It is possible that subconcussive blast exposure might cause direct structural damage to the brain or that other factors associated with blast exposure might play a role, the investigators added.
The relatively modest sample size and potential selection bias were cited by Dr. MacDonald and her associates as possible study limitations.
This study was funded by the Congressionally Directed Medical Research Programs. Dr. MacDonald and her associates reported no financial conflicts of interest.
FROM JAMA NEUROLOGY
Key clinical point: TBI itself, regardless of injury mechanism or the intensity of combat exposure, appears to be a "primary driver of adverse outcomes."
Major finding: Global outcomes as measured by the Glasgow Outcome Scale-Extended were "essentially indistinguishable" between blast-related and nonblast TBI, as were numerous neuropsychological abnormalities; neurobehavioral impairments; focal neurological deficits such as those affecting olfaction, gait, and limb ataxia; headache-related disability; PTSD and its components; depression; alcohol misuse; and sleep disturbances.
Data source: A prospective cohort study involving 178 military personnel who sustained blast-related TBI, TBI related to other, nonblast mechanisms, or other medical disorders and were assessed for a wide variety of adverse outcomes at 6 months and 12 months.
Disclosures: This study was funded by the Congressionally Directed Medical Research Programs. Dr. MacDonald and her associates reported no financial conflicts of interest.