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Pneumonitis with nivolumab treatment shows common radiographic patterns
A study of cancer patients enrolled in trials of the programmed cell death-1 inhibiting medicine nivolumab found that among a minority who developed pneumonitis during treatment, distinct radiographic patterns were significantly associated with the level of pneumonitis severity.
Investigators found that cryptic organizing pneumonia pattern (COP) was the most common, though not the most severe. Led by Mizuki Nishino, MD, of Brigham and Women’s Hospital, Boston, the researchers looked at the 20 patients out of a cohort of 170 (11.8%) who had developed pneumonitis, and found that radiologic patterns indicating acute interstitial pneumonia/acute respiratory distress syndrome (n = 2) had the highest severity grade on a scale of 1-5 (median 3), followed by those with COP pattern (n = 13, median grade 2), hypersensitivity pneumonitis (n = 2, median grade 1), and nonspecific interstitial pneumonia (n = 3, median grade 1). The pattern was significantly associated with severity (P = .0006).
The study cohort included patients being treated with nivolumab for lung cancer, melanoma, and lymphoma; the COP patten was the most common across tumor types and observed in patients receiving monotherapy and combination therapy alike. Therapy with nivolumab was suspended for all 20 pneumonitis patients, and most (n = 17) received treatment for pneumonitis with corticosteroids with or without infliximab, for a median treatment time of 6 weeks. Seven patients were able to restart nivolumab, though pneumonitis recurred in two, the investigators reported (Clin Cancer Res. 2016 Aug 17. doi: 10.1158/1078-0432.CCR-16-1320).
“Time from initiation of therapy to the development of pneumonitis had a wide range (0.5-11.5 months), indicating an importance of careful observation and follow-up for signs and symptoms of pneumonitis throughout treatment,” Dr. Nishino and colleagues wrote in their analysis, adding that shorter times were observed for lung cancer patients, possibly because of their higher pulmonary burden, a lower threshold for performing chest scans in these patients, or both. “In most patients, clinical and radiographic improvements were noted after treatment, indicating that [PD-1 inhibitor-related pneumonitis], although potentially serious, is treatable if diagnosed and managed appropriately. The observation emphasizes the importance of timely recognition, accurate diagnosis, and early intervention.”
The lead author and several coauthors disclosed funding from Bristol-Myers Squibb, which sponsored the trial, as well as from other manufacturers.
A study of cancer patients enrolled in trials of the programmed cell death-1 inhibiting medicine nivolumab found that among a minority who developed pneumonitis during treatment, distinct radiographic patterns were significantly associated with the level of pneumonitis severity.
Investigators found that cryptic organizing pneumonia pattern (COP) was the most common, though not the most severe. Led by Mizuki Nishino, MD, of Brigham and Women’s Hospital, Boston, the researchers looked at the 20 patients out of a cohort of 170 (11.8%) who had developed pneumonitis, and found that radiologic patterns indicating acute interstitial pneumonia/acute respiratory distress syndrome (n = 2) had the highest severity grade on a scale of 1-5 (median 3), followed by those with COP pattern (n = 13, median grade 2), hypersensitivity pneumonitis (n = 2, median grade 1), and nonspecific interstitial pneumonia (n = 3, median grade 1). The pattern was significantly associated with severity (P = .0006).
The study cohort included patients being treated with nivolumab for lung cancer, melanoma, and lymphoma; the COP patten was the most common across tumor types and observed in patients receiving monotherapy and combination therapy alike. Therapy with nivolumab was suspended for all 20 pneumonitis patients, and most (n = 17) received treatment for pneumonitis with corticosteroids with or without infliximab, for a median treatment time of 6 weeks. Seven patients were able to restart nivolumab, though pneumonitis recurred in two, the investigators reported (Clin Cancer Res. 2016 Aug 17. doi: 10.1158/1078-0432.CCR-16-1320).
“Time from initiation of therapy to the development of pneumonitis had a wide range (0.5-11.5 months), indicating an importance of careful observation and follow-up for signs and symptoms of pneumonitis throughout treatment,” Dr. Nishino and colleagues wrote in their analysis, adding that shorter times were observed for lung cancer patients, possibly because of their higher pulmonary burden, a lower threshold for performing chest scans in these patients, or both. “In most patients, clinical and radiographic improvements were noted after treatment, indicating that [PD-1 inhibitor-related pneumonitis], although potentially serious, is treatable if diagnosed and managed appropriately. The observation emphasizes the importance of timely recognition, accurate diagnosis, and early intervention.”
The lead author and several coauthors disclosed funding from Bristol-Myers Squibb, which sponsored the trial, as well as from other manufacturers.
A study of cancer patients enrolled in trials of the programmed cell death-1 inhibiting medicine nivolumab found that among a minority who developed pneumonitis during treatment, distinct radiographic patterns were significantly associated with the level of pneumonitis severity.
Investigators found that cryptic organizing pneumonia pattern (COP) was the most common, though not the most severe. Led by Mizuki Nishino, MD, of Brigham and Women’s Hospital, Boston, the researchers looked at the 20 patients out of a cohort of 170 (11.8%) who had developed pneumonitis, and found that radiologic patterns indicating acute interstitial pneumonia/acute respiratory distress syndrome (n = 2) had the highest severity grade on a scale of 1-5 (median 3), followed by those with COP pattern (n = 13, median grade 2), hypersensitivity pneumonitis (n = 2, median grade 1), and nonspecific interstitial pneumonia (n = 3, median grade 1). The pattern was significantly associated with severity (P = .0006).
The study cohort included patients being treated with nivolumab for lung cancer, melanoma, and lymphoma; the COP patten was the most common across tumor types and observed in patients receiving monotherapy and combination therapy alike. Therapy with nivolumab was suspended for all 20 pneumonitis patients, and most (n = 17) received treatment for pneumonitis with corticosteroids with or without infliximab, for a median treatment time of 6 weeks. Seven patients were able to restart nivolumab, though pneumonitis recurred in two, the investigators reported (Clin Cancer Res. 2016 Aug 17. doi: 10.1158/1078-0432.CCR-16-1320).
“Time from initiation of therapy to the development of pneumonitis had a wide range (0.5-11.5 months), indicating an importance of careful observation and follow-up for signs and symptoms of pneumonitis throughout treatment,” Dr. Nishino and colleagues wrote in their analysis, adding that shorter times were observed for lung cancer patients, possibly because of their higher pulmonary burden, a lower threshold for performing chest scans in these patients, or both. “In most patients, clinical and radiographic improvements were noted after treatment, indicating that [PD-1 inhibitor-related pneumonitis], although potentially serious, is treatable if diagnosed and managed appropriately. The observation emphasizes the importance of timely recognition, accurate diagnosis, and early intervention.”
The lead author and several coauthors disclosed funding from Bristol-Myers Squibb, which sponsored the trial, as well as from other manufacturers.
FROM CLINICAL CANCER RESEARCH
Key clinical point: Pneumonitis related to treatment with PD-1 inhibitors showed distinct radiographic patterns associated with severity; most cases resolved with corticosteroid treatment.
Major finding: Of 20 patients in nivolumab trials who developed pneumonitis, a COP pattern was seen in 13, and other patterns in 7; different patterns were significantly associated with pneumonitis severity (P = .006).
Data source: 170 patients with melanoma, lung cancer or lymphoma enrolled in single-site open-label clinical trial of nivolumab.
Disclosures: The lead author and several coauthors disclosed funding from Bristol-Myers Squibb, which sponsored the trial, as well as from other manufacturers.
Guillain-Barré incidence rose with Zika across Americas
Increased incidence of Guillain-Barré syndrome corresponded closely with patterns of Zika virus disease incidence in Central and South America from April 2015 through March 2016, according to results from a new temporal and graphic analysis.
The findings show Guillain-Barré syndrome (GBS) cases increasing from 100% to nearly 900% above previously recorded baseline rates during periods of Zika virus transmission in El Salvador, the Dominican Republic, Colombia, Honduras, Suriname, Venezuela, and the Brazilian state of Bahia (N Engl J Med. 2016 Aug 31. doi: 10.1056/NEJMc1609015).
The analysis of the yearlong period also revealed that declines in GBS incidence accompanied declines in Zika virus disease when and where transmission began to wane. The researchers, led by Marcos A. Espinal, MD, DrPH, of the Pan American Health Organization in Washington, did not find significant associations between co-circulation of dengue virus and GBS incidence. The study, which looked at 164,237 confirmed and suspected cases of Zika virus disease and 1,474 cases of GBS, found a 75% higher Zika virus disease incidence rate in women, which Dr. Espinal and colleagues said might be attributable to differences in health care–seeking behavior. GBS incidence, meanwhile, was 28% higher among males. The higher rate of GBS in men, the authors said, was consistent with findings from previous epidemiological studies of GBS.
While the new results did not show that Zika virus causes GBS, Dr. Espinal and colleagues wrote, they argued that they were indicative of a strong association, adding that GBS “could serve as a sentinel for Zika virus disease and other neurological disorders linked to Zika virus,” including microcephaly.
Most of the study authors worked for the Pan American Health Organization or for national health agencies in the data-contributing countries. None declared conflicts of interest.
Increased incidence of Guillain-Barré syndrome corresponded closely with patterns of Zika virus disease incidence in Central and South America from April 2015 through March 2016, according to results from a new temporal and graphic analysis.
The findings show Guillain-Barré syndrome (GBS) cases increasing from 100% to nearly 900% above previously recorded baseline rates during periods of Zika virus transmission in El Salvador, the Dominican Republic, Colombia, Honduras, Suriname, Venezuela, and the Brazilian state of Bahia (N Engl J Med. 2016 Aug 31. doi: 10.1056/NEJMc1609015).
The analysis of the yearlong period also revealed that declines in GBS incidence accompanied declines in Zika virus disease when and where transmission began to wane. The researchers, led by Marcos A. Espinal, MD, DrPH, of the Pan American Health Organization in Washington, did not find significant associations between co-circulation of dengue virus and GBS incidence. The study, which looked at 164,237 confirmed and suspected cases of Zika virus disease and 1,474 cases of GBS, found a 75% higher Zika virus disease incidence rate in women, which Dr. Espinal and colleagues said might be attributable to differences in health care–seeking behavior. GBS incidence, meanwhile, was 28% higher among males. The higher rate of GBS in men, the authors said, was consistent with findings from previous epidemiological studies of GBS.
While the new results did not show that Zika virus causes GBS, Dr. Espinal and colleagues wrote, they argued that they were indicative of a strong association, adding that GBS “could serve as a sentinel for Zika virus disease and other neurological disorders linked to Zika virus,” including microcephaly.
Most of the study authors worked for the Pan American Health Organization or for national health agencies in the data-contributing countries. None declared conflicts of interest.
Increased incidence of Guillain-Barré syndrome corresponded closely with patterns of Zika virus disease incidence in Central and South America from April 2015 through March 2016, according to results from a new temporal and graphic analysis.
The findings show Guillain-Barré syndrome (GBS) cases increasing from 100% to nearly 900% above previously recorded baseline rates during periods of Zika virus transmission in El Salvador, the Dominican Republic, Colombia, Honduras, Suriname, Venezuela, and the Brazilian state of Bahia (N Engl J Med. 2016 Aug 31. doi: 10.1056/NEJMc1609015).
The analysis of the yearlong period also revealed that declines in GBS incidence accompanied declines in Zika virus disease when and where transmission began to wane. The researchers, led by Marcos A. Espinal, MD, DrPH, of the Pan American Health Organization in Washington, did not find significant associations between co-circulation of dengue virus and GBS incidence. The study, which looked at 164,237 confirmed and suspected cases of Zika virus disease and 1,474 cases of GBS, found a 75% higher Zika virus disease incidence rate in women, which Dr. Espinal and colleagues said might be attributable to differences in health care–seeking behavior. GBS incidence, meanwhile, was 28% higher among males. The higher rate of GBS in men, the authors said, was consistent with findings from previous epidemiological studies of GBS.
While the new results did not show that Zika virus causes GBS, Dr. Espinal and colleagues wrote, they argued that they were indicative of a strong association, adding that GBS “could serve as a sentinel for Zika virus disease and other neurological disorders linked to Zika virus,” including microcephaly.
Most of the study authors worked for the Pan American Health Organization or for national health agencies in the data-contributing countries. None declared conflicts of interest.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Guidelines add two new heart failure treatments
Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.
The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.
Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.
Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.
The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.
For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.
Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.
The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.
About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.
Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.
The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.
Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.
Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.
The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.
For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.
Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.
The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.
About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.
Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.
The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.
Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.
Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.
The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.
For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.
Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.
The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.
About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.
FROM CIRCULATION
SFA-Popliteal Claudication: What’s Appropriate Care?
In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.
Speakers will be:
Dr. Mary McDermott of Northwestern University, on exercise;
Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;
Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;
Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;
Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and
Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.
VC: Why did you choose claudication as this year’s key theme?
Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.
VC: Is there too much of a leap in the vascular community to invasive interventions?
Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.
VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?
Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.
VC: What other cost and reimbursement issues do you expect to deal with during the symposium?
I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].
In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.
Speakers will be:
Dr. Mary McDermott of Northwestern University, on exercise;
Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;
Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;
Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;
Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and
Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.
VC: Why did you choose claudication as this year’s key theme?
Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.
VC: Is there too much of a leap in the vascular community to invasive interventions?
Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.
VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?
Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.
VC: What other cost and reimbursement issues do you expect to deal with during the symposium?
I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].
In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.
Speakers will be:
Dr. Mary McDermott of Northwestern University, on exercise;
Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;
Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;
Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;
Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and
Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.
VC: Why did you choose claudication as this year’s key theme?
Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.
VC: Is there too much of a leap in the vascular community to invasive interventions?
Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.
VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?
Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.
VC: What other cost and reimbursement issues do you expect to deal with during the symposium?
I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].
Clozapine REMS still plagued by problems
A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.
The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.
The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.
Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.
At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.
REMS applauded early on
Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.
However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.
The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.”
The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.
Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.
“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.
Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.
Problems ‘causing confusion’
Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.
Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.
By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.
“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.
The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”
Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”
Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”
Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.
Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”
The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.
A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.
The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.
The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.
Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.
At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.
REMS applauded early on
Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.
However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.
The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.”
The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.
Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.
“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.
Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.
Problems ‘causing confusion’
Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.
Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.
By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.
“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.
The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”
Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”
Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”
Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.
Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”
The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.
A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.
The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.
The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.
Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.
At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.
REMS applauded early on
Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.
However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.
The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.”
The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.
Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.
“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.
Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.
Problems ‘causing confusion’
Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.
Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.
By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.
“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.
The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”
Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”
Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”
Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.
Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”
The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.
CDC confirms Zika virus as a cause of microcephaly
Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.
The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.
In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.
Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.
For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.
The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.
The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”
Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.
The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.
In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.
Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.
For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.
The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.
The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”
Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.
The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.
In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.
Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.
For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.
The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.
The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”
FROM A CDC PRESS CONFERENCE
Cardiac cath lab work carries multiple risks
Workers performing fluoroscopically guided cardiovascular procedures are at significantly higher risk of a diverse array of health disorders compared with nonexposed subjects, according to a survey.
Though cancers and ocular, skin, and thyroid disorders are recognized risks of working with low-dose radiation, as are orthopedic problems associated with wearing heavy lead aprons, the new study, published online April 12 in Circulation: Cardiovascular Interventions, adds weight to emerging concerns about lesser-known risks.
In addition to higher prevalence of skin lesions, cataracts, thyroid disorders, cancer, and orthopedic problems, exposed workers saw significantly higher prevalence of hypertension, hypercholesterolemia, and depression or anxiety, compared with controls.
Maria Grazia Andreassi, Ph.D., of the CNR Institute of Clinical Physiology, in Pisa, Italy, led the study, which used questionnaires to collect health, exposure, and demographic information from 466 workers in cardiac catheterization laboratories in Italy: 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians. Radiation exposure was estimated based on subjects’ occupational radiological risk score (ORRS), which takes into consideration years of work, caseloads, and proximity to the radiation source in the lab.
The researchers administered the same questionnaires to 280 health workers who did not have occupational radiation exposure. The two groups were well matched for age, sex, education level, alcohol use, and body mass index, though current smoking differed significantly (27% of lab staff vs. 23% of unexposed workers).
As expected, orthopedic injuries were markedly higher among the lab workers, with 30% reporting disorders compared with 5% of controls (P less than .001). Nearly 5% of the lab workers had cataracts, compared with less than 1% of the nonexposed (P = .003), and risk increased for subjects with more years in the lab. Cancer was higher among exposed participants (2.6% vs. 0.7%), a difference that did not reach statistical significance. However, a significant trend was seen for cancer risk increasing across duration of exposure (Circ Cardiovasc Interv. 2016;9:e003273).
In the composite endpoint of cataract and cancer, a surrogate for disease associated with occupational exposure to radiation, the researchers found that the interventional cardiologists and electrophysiologists had a significantly higher prevalence than did the nurses and technicians (69% vs. 22% and 9%, respectively; P = .03).
Furthermore, the cancer in physicians occurred more often in the left side, when laterality was applicable, in 67% of cases, whereas the malignancy was left-sided in 33% of cancers occurring in nurses and technicians.
No significant differences in cardiovascular events were seen between the groups. However, hypertension and high cholesterol were more prevalent in cath lab workers, with adjusted odds ratios of 1.7 (95% confidence interval, 1-3; P = .05) and 2.9 (CI, 1-5; P = .004), respectively, for highly exposed subjects, compared with controls.
Last year, in a separate study, Dr. Andreassi’s group reported that exposure to low-dose radiation over time may increase carotid intima-media thickness, an early indicator of vascular injury, among cath lab workers (J Am Coll Cardiol Intv. 2015;8:616-27).
Anxiety and depression occurred in 12% of exposed subjects, compared with 2% of controls. The finding could reflect high occupational stress, the researchers wrote in their analysis, or may be an effect of radiation, “which is especially relevant on the unprotected head of the first operator and at chronic low doses may impact detrimentally on hippocampal neurogenesis and neuronal plasticity.”
The researchers acknowledged the possibility of selection bias in their study, favoring “a possible disproportionate contribution of respondents with existing health issues, who may reasonably think that their complaints are occupationally related,” they wrote. They also noted that the study was not designed to directly assess radiation dose, in part because dosimeters were not regularly worn in some of the settings where subjects worked. Finally, the radiation-exposed group had more cardiovascular risk factors. Nonetheless, the findings highlight the need to “spread the culture of safety” in cardiac cath labs, the researchers wrote.
There is now “more than enough information for us to conclude that the interventional catheterization laboratory is not a healthy workplace,” Dr. Lloyd W. Klein and Dr. Mugurel Bazavan of Advocate Illinois Masonic Medical Center, and Rush Medical College in Chicago, wrote in an accompanying editorial.
Finding “the courage to change business practice,” they wrote, “is the only path to innovative cath laboratory design and shielding techniques that can prevent these occupational hazards” (Circ Cardiovasc Interv. 2016;9:e003742).
Dr. Andreassi and colleagues disclosed no conflicts of interest related to their study, and Dr. Klein and Dr. Bazavan disclosed no conflicts related to their editorial.
The field of interventional cardiology is tremendously exciting, and yet the long-term risks are not as well defined as they should be for the protection of cath lab personnel.
 |
Dr. Charles E. Chambers |
This study shows strikingly that both physicians and nonphysicians are at increased risk of a diverse group of medical conditions. Quantifying the contribution of radiation exposure to CV risk and separating it from smoking, dietary, and other factors, will require studies using dosimetry data in lieu of the estimated exposure measures seen in this study.
However, as these findings underscore, there is no doubt that we must be concerned about radiation and that manufacturers, hospitals, and providers need to come to the table to address these urgent questions of personal liability and workplace safety, particularly with so many young people entering the field.
Dr. Charles E. Chambers is professor of medicine and radiology at Pennsylvania State University, Hershey, and past president of the Society for Cardiovascular Angiography and Interventions. He made these comments in an interview, and reports no conflicts of interest.
The field of interventional cardiology is tremendously exciting, and yet the long-term risks are not as well defined as they should be for the protection of cath lab personnel.
|
Dr. Charles E. Chambers |
This study shows strikingly that both physicians and nonphysicians are at increased risk of a diverse group of medical conditions. Quantifying the contribution of radiation exposure to CV risk and separating it from smoking, dietary, and other factors, will require studies using dosimetry data in lieu of the estimated exposure measures seen in this study.
However, as these findings underscore, there is no doubt that we must be concerned about radiation and that manufacturers, hospitals, and providers need to come to the table to address these urgent questions of personal liability and workplace safety, particularly with so many young people entering the field.
Dr. Charles E. Chambers is professor of medicine and radiology at Pennsylvania State University, Hershey, and past president of the Society for Cardiovascular Angiography and Interventions. He made these comments in an interview, and reports no conflicts of interest.
The field of interventional cardiology is tremendously exciting, and yet the long-term risks are not as well defined as they should be for the protection of cath lab personnel.
|
Dr. Charles E. Chambers |
This study shows strikingly that both physicians and nonphysicians are at increased risk of a diverse group of medical conditions. Quantifying the contribution of radiation exposure to CV risk and separating it from smoking, dietary, and other factors, will require studies using dosimetry data in lieu of the estimated exposure measures seen in this study.
However, as these findings underscore, there is no doubt that we must be concerned about radiation and that manufacturers, hospitals, and providers need to come to the table to address these urgent questions of personal liability and workplace safety, particularly with so many young people entering the field.
Dr. Charles E. Chambers is professor of medicine and radiology at Pennsylvania State University, Hershey, and past president of the Society for Cardiovascular Angiography and Interventions. He made these comments in an interview, and reports no conflicts of interest.
Workers performing fluoroscopically guided cardiovascular procedures are at significantly higher risk of a diverse array of health disorders compared with nonexposed subjects, according to a survey.
Though cancers and ocular, skin, and thyroid disorders are recognized risks of working with low-dose radiation, as are orthopedic problems associated with wearing heavy lead aprons, the new study, published online April 12 in Circulation: Cardiovascular Interventions, adds weight to emerging concerns about lesser-known risks.
In addition to higher prevalence of skin lesions, cataracts, thyroid disorders, cancer, and orthopedic problems, exposed workers saw significantly higher prevalence of hypertension, hypercholesterolemia, and depression or anxiety, compared with controls.
Maria Grazia Andreassi, Ph.D., of the CNR Institute of Clinical Physiology, in Pisa, Italy, led the study, which used questionnaires to collect health, exposure, and demographic information from 466 workers in cardiac catheterization laboratories in Italy: 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians. Radiation exposure was estimated based on subjects’ occupational radiological risk score (ORRS), which takes into consideration years of work, caseloads, and proximity to the radiation source in the lab.
The researchers administered the same questionnaires to 280 health workers who did not have occupational radiation exposure. The two groups were well matched for age, sex, education level, alcohol use, and body mass index, though current smoking differed significantly (27% of lab staff vs. 23% of unexposed workers).
As expected, orthopedic injuries were markedly higher among the lab workers, with 30% reporting disorders compared with 5% of controls (P less than .001). Nearly 5% of the lab workers had cataracts, compared with less than 1% of the nonexposed (P = .003), and risk increased for subjects with more years in the lab. Cancer was higher among exposed participants (2.6% vs. 0.7%), a difference that did not reach statistical significance. However, a significant trend was seen for cancer risk increasing across duration of exposure (Circ Cardiovasc Interv. 2016;9:e003273).
In the composite endpoint of cataract and cancer, a surrogate for disease associated with occupational exposure to radiation, the researchers found that the interventional cardiologists and electrophysiologists had a significantly higher prevalence than did the nurses and technicians (69% vs. 22% and 9%, respectively; P = .03).
Furthermore, the cancer in physicians occurred more often in the left side, when laterality was applicable, in 67% of cases, whereas the malignancy was left-sided in 33% of cancers occurring in nurses and technicians.
No significant differences in cardiovascular events were seen between the groups. However, hypertension and high cholesterol were more prevalent in cath lab workers, with adjusted odds ratios of 1.7 (95% confidence interval, 1-3; P = .05) and 2.9 (CI, 1-5; P = .004), respectively, for highly exposed subjects, compared with controls.
Last year, in a separate study, Dr. Andreassi’s group reported that exposure to low-dose radiation over time may increase carotid intima-media thickness, an early indicator of vascular injury, among cath lab workers (J Am Coll Cardiol Intv. 2015;8:616-27).
Anxiety and depression occurred in 12% of exposed subjects, compared with 2% of controls. The finding could reflect high occupational stress, the researchers wrote in their analysis, or may be an effect of radiation, “which is especially relevant on the unprotected head of the first operator and at chronic low doses may impact detrimentally on hippocampal neurogenesis and neuronal plasticity.”
The researchers acknowledged the possibility of selection bias in their study, favoring “a possible disproportionate contribution of respondents with existing health issues, who may reasonably think that their complaints are occupationally related,” they wrote. They also noted that the study was not designed to directly assess radiation dose, in part because dosimeters were not regularly worn in some of the settings where subjects worked. Finally, the radiation-exposed group had more cardiovascular risk factors. Nonetheless, the findings highlight the need to “spread the culture of safety” in cardiac cath labs, the researchers wrote.
There is now “more than enough information for us to conclude that the interventional catheterization laboratory is not a healthy workplace,” Dr. Lloyd W. Klein and Dr. Mugurel Bazavan of Advocate Illinois Masonic Medical Center, and Rush Medical College in Chicago, wrote in an accompanying editorial.
Finding “the courage to change business practice,” they wrote, “is the only path to innovative cath laboratory design and shielding techniques that can prevent these occupational hazards” (Circ Cardiovasc Interv. 2016;9:e003742).
Dr. Andreassi and colleagues disclosed no conflicts of interest related to their study, and Dr. Klein and Dr. Bazavan disclosed no conflicts related to their editorial.
Workers performing fluoroscopically guided cardiovascular procedures are at significantly higher risk of a diverse array of health disorders compared with nonexposed subjects, according to a survey.
Though cancers and ocular, skin, and thyroid disorders are recognized risks of working with low-dose radiation, as are orthopedic problems associated with wearing heavy lead aprons, the new study, published online April 12 in Circulation: Cardiovascular Interventions, adds weight to emerging concerns about lesser-known risks.
In addition to higher prevalence of skin lesions, cataracts, thyroid disorders, cancer, and orthopedic problems, exposed workers saw significantly higher prevalence of hypertension, hypercholesterolemia, and depression or anxiety, compared with controls.
Maria Grazia Andreassi, Ph.D., of the CNR Institute of Clinical Physiology, in Pisa, Italy, led the study, which used questionnaires to collect health, exposure, and demographic information from 466 workers in cardiac catheterization laboratories in Italy: 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians. Radiation exposure was estimated based on subjects’ occupational radiological risk score (ORRS), which takes into consideration years of work, caseloads, and proximity to the radiation source in the lab.
The researchers administered the same questionnaires to 280 health workers who did not have occupational radiation exposure. The two groups were well matched for age, sex, education level, alcohol use, and body mass index, though current smoking differed significantly (27% of lab staff vs. 23% of unexposed workers).
As expected, orthopedic injuries were markedly higher among the lab workers, with 30% reporting disorders compared with 5% of controls (P less than .001). Nearly 5% of the lab workers had cataracts, compared with less than 1% of the nonexposed (P = .003), and risk increased for subjects with more years in the lab. Cancer was higher among exposed participants (2.6% vs. 0.7%), a difference that did not reach statistical significance. However, a significant trend was seen for cancer risk increasing across duration of exposure (Circ Cardiovasc Interv. 2016;9:e003273).
In the composite endpoint of cataract and cancer, a surrogate for disease associated with occupational exposure to radiation, the researchers found that the interventional cardiologists and electrophysiologists had a significantly higher prevalence than did the nurses and technicians (69% vs. 22% and 9%, respectively; P = .03).
Furthermore, the cancer in physicians occurred more often in the left side, when laterality was applicable, in 67% of cases, whereas the malignancy was left-sided in 33% of cancers occurring in nurses and technicians.
No significant differences in cardiovascular events were seen between the groups. However, hypertension and high cholesterol were more prevalent in cath lab workers, with adjusted odds ratios of 1.7 (95% confidence interval, 1-3; P = .05) and 2.9 (CI, 1-5; P = .004), respectively, for highly exposed subjects, compared with controls.
Last year, in a separate study, Dr. Andreassi’s group reported that exposure to low-dose radiation over time may increase carotid intima-media thickness, an early indicator of vascular injury, among cath lab workers (J Am Coll Cardiol Intv. 2015;8:616-27).
Anxiety and depression occurred in 12% of exposed subjects, compared with 2% of controls. The finding could reflect high occupational stress, the researchers wrote in their analysis, or may be an effect of radiation, “which is especially relevant on the unprotected head of the first operator and at chronic low doses may impact detrimentally on hippocampal neurogenesis and neuronal plasticity.”
The researchers acknowledged the possibility of selection bias in their study, favoring “a possible disproportionate contribution of respondents with existing health issues, who may reasonably think that their complaints are occupationally related,” they wrote. They also noted that the study was not designed to directly assess radiation dose, in part because dosimeters were not regularly worn in some of the settings where subjects worked. Finally, the radiation-exposed group had more cardiovascular risk factors. Nonetheless, the findings highlight the need to “spread the culture of safety” in cardiac cath labs, the researchers wrote.
There is now “more than enough information for us to conclude that the interventional catheterization laboratory is not a healthy workplace,” Dr. Lloyd W. Klein and Dr. Mugurel Bazavan of Advocate Illinois Masonic Medical Center, and Rush Medical College in Chicago, wrote in an accompanying editorial.
Finding “the courage to change business practice,” they wrote, “is the only path to innovative cath laboratory design and shielding techniques that can prevent these occupational hazards” (Circ Cardiovasc Interv. 2016;9:e003742).
Dr. Andreassi and colleagues disclosed no conflicts of interest related to their study, and Dr. Klein and Dr. Bazavan disclosed no conflicts related to their editorial.
FROM CIRCULATION: CARDIOVASCULAR INTERVENTIONS
Key clinical point: Workers in cardiac catheterization labs exposed to ionizing radiation are at risk of a wide array of health disorders.
Major finding: Prevalences of skin lesions, orthopedic illness, cataract, hypertension, hypercholesterolemia, and anxiety/depression were significantly higher in exposed cath lab workers, compared with other health care workers.
Data source: A multicenter, controlled study of 746 Italian physicians and staff (466 exposed to radiation and 280 matched unexposed controls) completing self-administered questionnaires.
Disclosures: None.
High-dose vitamin D improves heart structure, function in chronic heart failure
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study.
However, the same study. led by Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – the study’s primary outcome measure – was not improved after a year’s supplementation with vitamin D.
It is unclear why vitamin D deficiency co-occurs in a majority of people with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle.
The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).
Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (MWT) and echocardiography findings were recorded at baseline and follow-up.
Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment.
“There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance but there were statistically significant, and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis.
The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering.
“Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote.
The investigators championed the addition of vitamin D3 to CHF treatment regimens.
As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
FROM ACC16
Key clinical point: Oral supplementation of high-dose vitamin D3 led to significantly improved left ventricular function and structure in a cohort of vitamin-deficient patients.
Major finding: Treated patients had significantly improved left ventricular ejection fraction of +6.07% vs. nontreated patients at 1 year, and significant reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm and left ventricular end systolic diameter –2.09 mm).
Data source: A single-site randomized trial in which 229 patients with LV CHF received high-dose vitamin D or placebo for 12 months.
Disclosures: The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.
Self-expanding TAVR bests surgery based on 3-year stroke and death risks
Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.
Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.
The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.
Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.
At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.
While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.
While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.
The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.
Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.
Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.
The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.
Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.
At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.
While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.
While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.
The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.
Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.
Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.
The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.
Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.
At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.
While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.
While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.
The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.
FROM ACC 2016
Key clinical point: Patients randomized to self-expanding TAVR or open surgical aortic valve replacement were less likely to have died or had a stroke at 3 years post-procedure
Major finding:. Three-year all-cause mortality and stroke rate was significantly lower in TAVR patients – 37% versus nearly 47% in SAVR patients.
Data source: A cohort of 750 patients deemed high risk who underwent open aortic valve replacement or TAVR after randomization; procedures performed at 45 sites
Disclosures: The study was sponsored by Medtronic, maker of the self-expanding transcatheter technology. Most study authors, though not the lead author, had direct financial involvement.
CDC urges states to prepare for Zika
As warmer weather raises the possibility of local Zika virus transmission in the continental United States, federal health officials are pushing state and local governments to devise plans aimed at protecting pregnant women from infection, to increase access to contraception, and to ensure better coordination by mosquito control districts.
On April 1, the U.S. Centers for Disease Prevention and Control hosted a day-long seminar on Zika attended by some 300 state and local public health professionals. Zika virus, which is increasingly linked to adverse fetal outcomes including microcephaly, is now spreading in Puerto Rico, the U.S. Virgin Islands, and American Samoa.
Though most of the U.S. response effort is currently concentrated in Puerto Rico, and no local transmission has yet been reported in the continental U.S., a CDC report issued concurrently with the conference highlighted the potential for Zika transmission within the U.S. The entire southern half of the continental U.S., and much of its east coast, is home to the Aedes aegypti mosquitoes that can carry Zika virus.
In the same report, CDC also stressed that pregnant women should avoid travel to areas where Zika is being rapidly transmitted, and avoid sexual contact or consistently use condoms with partners who “reside in or have traveled to areas with active Zika virus transmission.”
“The key here is to reduce the risk to pregnant women,” Dr. Tom Frieden, CDC director, said at a news conference during the meeting. “There is an urgent need for all of us to learn more and do more,” he noted, acknowledging that officials had concerns about securing sufficient federal funding, getting rapid screening tools commercially developed in the absence of such funding, and improving the capabilities of U.S. mosquito control districts in the states most likely to be affected.
As local clusters of dengue virus disease have occurred in Florida, Texas, and Hawaii, Dr. Frieden said these states need to be particularly responsive to the Zika threat. However, Zika transmission could follow a different pattern, he said.
While Dr. Frieden described some local mosquito control districts and their capabilities as robust, others are considerably less so. Many districts in vulnerable states are not contiguous, leading to potential gaps in vector control. Dr. Frieden noted that even where control is most intensive, such as in Puerto Rico, vector resistance to common pesticides is a problem.
Dr. Frieden also stressed the importance of widening local access to contraception. He clarified that the CDC was not advising couples to avoid or delay pregnancy, even in Puerto Rico. However, he said, “if a woman and her partner choose not to become pregnant [there should be] ready access to effective contraception,” particularly the long-term reversible methods likely to be most effective.
Amy Pope, deputy homeland security advisor in the Obama administration, underscored the concern about Zika-specific funding. In February, the administration requested some $1.9 billion from Congress to combat Zika, including by improving access to contraception, developing vaccines and diagnostics, and other efforts. This funding has yet to be approved, Ms. Pope noted, adding that some members of Congress proposed redirecting funding that had been earmarked to combat Ebola.
“Congress is asking the American people to choose which disease it wants the most protection from,” Ms. Pope said, and Dr. Frieden reminded the conference that the Ebola crisis was not over. A new case from Liberia was announced April 1, he noted, and an ongoing cluster of transmission is occurring in Guinea.
As warmer weather raises the possibility of local Zika virus transmission in the continental United States, federal health officials are pushing state and local governments to devise plans aimed at protecting pregnant women from infection, to increase access to contraception, and to ensure better coordination by mosquito control districts.
On April 1, the U.S. Centers for Disease Prevention and Control hosted a day-long seminar on Zika attended by some 300 state and local public health professionals. Zika virus, which is increasingly linked to adverse fetal outcomes including microcephaly, is now spreading in Puerto Rico, the U.S. Virgin Islands, and American Samoa.
Though most of the U.S. response effort is currently concentrated in Puerto Rico, and no local transmission has yet been reported in the continental U.S., a CDC report issued concurrently with the conference highlighted the potential for Zika transmission within the U.S. The entire southern half of the continental U.S., and much of its east coast, is home to the Aedes aegypti mosquitoes that can carry Zika virus.
In the same report, CDC also stressed that pregnant women should avoid travel to areas where Zika is being rapidly transmitted, and avoid sexual contact or consistently use condoms with partners who “reside in or have traveled to areas with active Zika virus transmission.”
“The key here is to reduce the risk to pregnant women,” Dr. Tom Frieden, CDC director, said at a news conference during the meeting. “There is an urgent need for all of us to learn more and do more,” he noted, acknowledging that officials had concerns about securing sufficient federal funding, getting rapid screening tools commercially developed in the absence of such funding, and improving the capabilities of U.S. mosquito control districts in the states most likely to be affected.
As local clusters of dengue virus disease have occurred in Florida, Texas, and Hawaii, Dr. Frieden said these states need to be particularly responsive to the Zika threat. However, Zika transmission could follow a different pattern, he said.
While Dr. Frieden described some local mosquito control districts and their capabilities as robust, others are considerably less so. Many districts in vulnerable states are not contiguous, leading to potential gaps in vector control. Dr. Frieden noted that even where control is most intensive, such as in Puerto Rico, vector resistance to common pesticides is a problem.
Dr. Frieden also stressed the importance of widening local access to contraception. He clarified that the CDC was not advising couples to avoid or delay pregnancy, even in Puerto Rico. However, he said, “if a woman and her partner choose not to become pregnant [there should be] ready access to effective contraception,” particularly the long-term reversible methods likely to be most effective.
Amy Pope, deputy homeland security advisor in the Obama administration, underscored the concern about Zika-specific funding. In February, the administration requested some $1.9 billion from Congress to combat Zika, including by improving access to contraception, developing vaccines and diagnostics, and other efforts. This funding has yet to be approved, Ms. Pope noted, adding that some members of Congress proposed redirecting funding that had been earmarked to combat Ebola.
“Congress is asking the American people to choose which disease it wants the most protection from,” Ms. Pope said, and Dr. Frieden reminded the conference that the Ebola crisis was not over. A new case from Liberia was announced April 1, he noted, and an ongoing cluster of transmission is occurring in Guinea.
As warmer weather raises the possibility of local Zika virus transmission in the continental United States, federal health officials are pushing state and local governments to devise plans aimed at protecting pregnant women from infection, to increase access to contraception, and to ensure better coordination by mosquito control districts.
On April 1, the U.S. Centers for Disease Prevention and Control hosted a day-long seminar on Zika attended by some 300 state and local public health professionals. Zika virus, which is increasingly linked to adverse fetal outcomes including microcephaly, is now spreading in Puerto Rico, the U.S. Virgin Islands, and American Samoa.
Though most of the U.S. response effort is currently concentrated in Puerto Rico, and no local transmission has yet been reported in the continental U.S., a CDC report issued concurrently with the conference highlighted the potential for Zika transmission within the U.S. The entire southern half of the continental U.S., and much of its east coast, is home to the Aedes aegypti mosquitoes that can carry Zika virus.
In the same report, CDC also stressed that pregnant women should avoid travel to areas where Zika is being rapidly transmitted, and avoid sexual contact or consistently use condoms with partners who “reside in or have traveled to areas with active Zika virus transmission.”
“The key here is to reduce the risk to pregnant women,” Dr. Tom Frieden, CDC director, said at a news conference during the meeting. “There is an urgent need for all of us to learn more and do more,” he noted, acknowledging that officials had concerns about securing sufficient federal funding, getting rapid screening tools commercially developed in the absence of such funding, and improving the capabilities of U.S. mosquito control districts in the states most likely to be affected.
As local clusters of dengue virus disease have occurred in Florida, Texas, and Hawaii, Dr. Frieden said these states need to be particularly responsive to the Zika threat. However, Zika transmission could follow a different pattern, he said.
While Dr. Frieden described some local mosquito control districts and their capabilities as robust, others are considerably less so. Many districts in vulnerable states are not contiguous, leading to potential gaps in vector control. Dr. Frieden noted that even where control is most intensive, such as in Puerto Rico, vector resistance to common pesticides is a problem.
Dr. Frieden also stressed the importance of widening local access to contraception. He clarified that the CDC was not advising couples to avoid or delay pregnancy, even in Puerto Rico. However, he said, “if a woman and her partner choose not to become pregnant [there should be] ready access to effective contraception,” particularly the long-term reversible methods likely to be most effective.
Amy Pope, deputy homeland security advisor in the Obama administration, underscored the concern about Zika-specific funding. In February, the administration requested some $1.9 billion from Congress to combat Zika, including by improving access to contraception, developing vaccines and diagnostics, and other efforts. This funding has yet to be approved, Ms. Pope noted, adding that some members of Congress proposed redirecting funding that had been earmarked to combat Ebola.
“Congress is asking the American people to choose which disease it wants the most protection from,” Ms. Pope said, and Dr. Frieden reminded the conference that the Ebola crisis was not over. A new case from Liberia was announced April 1, he noted, and an ongoing cluster of transmission is occurring in Guinea.
