User login
Does education to enhance maternal awareness of fetal movements help reduce stillbirth?
WHAT DOES THIS MEAN FOR PRACTICE?
- Data indicate that fetal movement counting does not help to reduce stillbirth incidence
- Continue to use fetal movement counting to maintain patient engagement in managing her own pregnancy
- Encourage fetal movement awareness but also counsel patients that awareness does not reduce stillbirth
- This may decrease a patient’s feelings of guilt (because she did not maintain fetal kick counting) should a stillbirth occur
Neurologic Disease Eventually Affects Half of Women and One-Third of Men
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Findings strengthen the call for prioritizing the focus on preventive interventions at the population level.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online ahead of print October 2 in the Journal of Neurology, Neurosurgery & Psychiatry.
The population-based Rotterdam study involved 12,102 individuals (57.7% women) who were ages 45 or older and free of neurologic disease at baseline. This cohort was followed for 26 years. Silvan Licher, a PhD student in the Department of Epidemiology at Erasmus MC University Medical Center Rotterdam in the Netherlands, and colleagues found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women age 45 had a significantly higher lifetime risk than men of developing dementia (31.4% vs 18.6%, respectively) and stroke (21.6% vs 19.3%), but the risk of parkinsonism was similar between the sexes. Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs 3.1%), largely because of the overlap between dementia and stroke.
At age 45, women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85, 66.6% of first diagnoses in women and 55.6% in men were dementia. By comparison, first manifestation of stroke was the greatest threat to men age 45. Men also were at a significantly higher risk for stroke at a younger age—before age 75—than were women (8.4% vs 5.8%, respectively). In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke and was relatively low after age 85, with no significant differences in risk between men and women.
The authors considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a one-, two-, or three-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals age 45 or older, and a greater than 50% reduction in risk in the oldest. A three-year delay in the onset of dementia reduced the lifetime risk by 15% for men and women age 45 and conveyed a 30% reduction in risk to those age 45 or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission and the Municipality of Rotterdam; the Netherlands Consortium for Healthy Aging; and the Dutch Heart Foundation.
—Bianca Nogrady
Suggested Reading
Licher S, Darweesh SKL, Wolters FJ, et al. Lifetime risk of common neurological diseases in the elderly population. J Neurol Neurosurg Psychiatry. 2018 Oct 2 [Epub ahead of print].
Be judicious with empiric antibiotics for febrile neutropenia
SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.
Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.
“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.
“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.
Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”
For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.
A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.
Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.
Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).
Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).
Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).
Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.
SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.
Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.
“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.
“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.
Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”
For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.
A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.
Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.
Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).
Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).
Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).
Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.
SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.
Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.
“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.
“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.
Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”
For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.
A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.
Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.
Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).
Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).
Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).
Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.
EXPERT ANALYSIS FROM IDWEEK 2018
How to Identify Frontal Fibrosing Alopecia
Home-based exercise for PAD tops supervised treadmill exercise
CHICAGO – Home-based exercise for peripheral arterial disease–related walking limitations works at least as well as – and arguably better than – the supervised outpatient hospital clinic-based treadmill exercise programs of the type approved for coverage by the Centers for Medicare and Medicaid Services in 2017, Mary M. McDermott, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
“The prevailing thinking is that supervised treadmill exercise is more effective than home-based exercise for PAD. And for the outcome of treadmill walking that is true. But for the outcome of 6-minute walking distance, which I would argue is more relevant to walking in daily life, home-based exercise programs appear to be better. Supervised treadmill exercise interventions preferentially improve treadmill walking performance, and that doesn’t translate as well to walking in daily life. Home-based exercise, where patients walk in a corridor or on the ground, is more relevant to the type of walking that they want to do,” explained Dr. McDermott, professor of medicine at the university as well as a leader in the field of research on exercise as a treatment for PAD.
However, she added a caveat regarding home-based exercise for symptomatic PAD: For it to be effective it must incorporate proven behavioral change techniques, including goal setting, monitoring progress, accountability to a coach, and face-to-face visits at least once per month.
“It seems you can’t just tell PAD patients to go home and walk because most of them won’t do it,” observed Dr. McDermott, who is a general internist and geriatrician.
Home-based exercise programs aren’t reimbursed by the CMS. But studies by Dr. McDermott and other investigators indicate that the results are more durable than for supervised treadmill exercise. For example, in the Group Oriented Arterial Leg Study (GOALS) – a 6-month group-mediated cognitive behavioral intervention in which PAD patients built up to walking at home for up to 50 minutes per session 5 days per week – 6-minute walking distance (6MWD) remained significantly better than in controls at follow-up after completion of the intervention. In fact, 6MWD actually increased further between 6 and 12 months in the home exercise group (J Am Heart Assoc. 2014 May 21;3(3):e000711. doi: 10.1161/JAHA.113.000711). Dr. McDermott was the lead author for this study.
In contrast, another study by Dr. McDermott now in press for the same journal found that the improvement in 6MWD achieved in PAD patients over the course of a 6-month supervised treadmill exercise program was not maintained during the next 6 months after completion of the intervention. Indeed, 6MWD showed a steady decline from its apex at the intervention’s conclusion, such that at the 12-month mark it was no longer significantly different from that of the control group, according to Dr. McDermott.
The Society for Vascular Surgery recommends a supervised exercise program as first-line therapy for PAD patients with intermittent claudication, with a Class I Level of Evidence A designation. Home-based exercise also gets a Class I recommendation, albeit with Level of Evidence B.
Dr. McDermott believes a home exercise program makes the most sense for PAD patients after their CMS benefit for a supervised clinic-based program has run out, or for patients – and there are a great many – who either can’t or don’t want to participate in a supervised program. She and others who’ve led randomized controlled trials of supervised exercise programs have found that close to 70% of eligible PAD patients decline to participate because of the inconvenience of going to the hospital outpatient facility at least three times per week or for other reasons.
“Also, it’s important to recognize that attendance can be a challenge, even when supervised exercise is covered by insurance. In our randomized trials, where we provide transportation, we still see only 65%-70% adherence to attendance,” she noted.
She stressed that it’s crucial for physicians and surgeons to educate their PAD patients about what to expect from an exercise program, be it supervised or home based.
“It’s not like revascularization, where they’re going to feel better in their walking immediately. It really takes a commitment. Four to six weeks is usually required before patients begin to experience a benefit, and I think it’s really important for patients to know that so they don’t get discouraged in the first couple of weeks,” Dr. McDermott said.
Turning to the key evidence-based behavioral change techniques shared by successful home-exercise programs for PAD, she noted that the GOALS trial intervention utilized weekly group sessions in which simple cognitive behavioral self-regulatory techniques were used to help patients set and stick to home-based walking goals. A similarly positive randomized controlled trial by investigators at the University of Oklahoma utilized once-monthly group meetings at the medical center (J Am Heart Assoc. 2014 Sep 18;3(5):e001107. doi: 10.1161/JAHA.114.001107).
In contrast, in the recent HONOR randomized clinical trial, where Dr. McDermott and her coinvestigators tested whether a home-based exercise intervention in which the active treatment group utilized a Fitbit wearable activity monitor and telephone coaching over the course of 9 months, the results proved disappointing. The intervention was no more effective than was usual care at improving 6MWD (JAMA. 2018 Apr 24;319(16):1665-76).
“One of the things I learned from doing this trial is that for a home-based exercise intervention in PAD to be successful, it’s not easy and there really needs to be some ongoing contact with a coach or nurse or a staff member that the patient feels accountable to. A wearable device is not a durably effective motivator for PAD patients. I think the reason this trial didn’t work so well is that most of it was by telephone and it was easy for patients to avoid our calls if they weren’t walking. Patients were initially really enthusiastic about the Fitbit, but we found that over time they stopped wearing it,” she said.
Dr. McDermott heartily endorses the Society for Vascular Surgery’s Class I recommendation that all PAD patients with intermittent claudication should exercise regularly, including those who’ve undergone revascularization procedures. Numerous clinical trials have demonstrated additive clinical benefits for opening the peripheral artery and strengthening skeletal muscles.
Uptake of supervised exercise programs for symptomatic PAD since the CMS coverage decision is quite variable regionally. Integrating new programs into existing cardiac rehabilitation facilities is a natural fit because staff members are very familiar with structured treadmill exercises already on site, but some freestanding programs are run by vascular surgery groups or cardiologists.
“I think part of the reason it hasn’t been taken up faster is that the reimbursement is such that you’re not going to make money on it,” Dr. McDermott said.
Asked if all patients with PAD should undergo an exercise treadmill test before embarking on an exercise program, Dr. McDermott replied, “I’m part of a writing group for the American Heart Association on how to implement these new guidelines. We’re not formally recommending a stress test. Some cardiologists on the panel suggested that it should be individualized based on patient history and symptoms. If they’re having symptoms of chest pain or they have a significant cardiac history, go ahead with a stress test. I don’t think it’s going to be recommended as a routine practice, but it’s safest to get a stress test.”
She reported having no financial conflicts regarding her presentation.
Requirements for CMS coverage of supervised exercise for symptomatic PAD
*The exercise program must consist of 12 weeks of thrice-weekly sessions.
*It has to be prescribed by a physician following a face-to-face meeting with the patient during which the physician provides education on cardiovascular risk prevention.
*An additional 36 sessions of supervised exercise can be obtained with a written note of justification by the physician following completion of the initial 12 weeks.
*The sessions must take place in a physician’s office or an outpatient hospital setting.
*The exercise has to be supervised by a physician, physician assistant, or nurse specialist.
*The exercise must be delivered by qualified personnel trained in basic and advanced cardiac life support as well as exercise therapy for PAD.
CHICAGO – Home-based exercise for peripheral arterial disease–related walking limitations works at least as well as – and arguably better than – the supervised outpatient hospital clinic-based treadmill exercise programs of the type approved for coverage by the Centers for Medicare and Medicaid Services in 2017, Mary M. McDermott, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
“The prevailing thinking is that supervised treadmill exercise is more effective than home-based exercise for PAD. And for the outcome of treadmill walking that is true. But for the outcome of 6-minute walking distance, which I would argue is more relevant to walking in daily life, home-based exercise programs appear to be better. Supervised treadmill exercise interventions preferentially improve treadmill walking performance, and that doesn’t translate as well to walking in daily life. Home-based exercise, where patients walk in a corridor or on the ground, is more relevant to the type of walking that they want to do,” explained Dr. McDermott, professor of medicine at the university as well as a leader in the field of research on exercise as a treatment for PAD.
However, she added a caveat regarding home-based exercise for symptomatic PAD: For it to be effective it must incorporate proven behavioral change techniques, including goal setting, monitoring progress, accountability to a coach, and face-to-face visits at least once per month.
“It seems you can’t just tell PAD patients to go home and walk because most of them won’t do it,” observed Dr. McDermott, who is a general internist and geriatrician.
Home-based exercise programs aren’t reimbursed by the CMS. But studies by Dr. McDermott and other investigators indicate that the results are more durable than for supervised treadmill exercise. For example, in the Group Oriented Arterial Leg Study (GOALS) – a 6-month group-mediated cognitive behavioral intervention in which PAD patients built up to walking at home for up to 50 minutes per session 5 days per week – 6-minute walking distance (6MWD) remained significantly better than in controls at follow-up after completion of the intervention. In fact, 6MWD actually increased further between 6 and 12 months in the home exercise group (J Am Heart Assoc. 2014 May 21;3(3):e000711. doi: 10.1161/JAHA.113.000711). Dr. McDermott was the lead author for this study.
In contrast, another study by Dr. McDermott now in press for the same journal found that the improvement in 6MWD achieved in PAD patients over the course of a 6-month supervised treadmill exercise program was not maintained during the next 6 months after completion of the intervention. Indeed, 6MWD showed a steady decline from its apex at the intervention’s conclusion, such that at the 12-month mark it was no longer significantly different from that of the control group, according to Dr. McDermott.
The Society for Vascular Surgery recommends a supervised exercise program as first-line therapy for PAD patients with intermittent claudication, with a Class I Level of Evidence A designation. Home-based exercise also gets a Class I recommendation, albeit with Level of Evidence B.
Dr. McDermott believes a home exercise program makes the most sense for PAD patients after their CMS benefit for a supervised clinic-based program has run out, or for patients – and there are a great many – who either can’t or don’t want to participate in a supervised program. She and others who’ve led randomized controlled trials of supervised exercise programs have found that close to 70% of eligible PAD patients decline to participate because of the inconvenience of going to the hospital outpatient facility at least three times per week or for other reasons.
“Also, it’s important to recognize that attendance can be a challenge, even when supervised exercise is covered by insurance. In our randomized trials, where we provide transportation, we still see only 65%-70% adherence to attendance,” she noted.
She stressed that it’s crucial for physicians and surgeons to educate their PAD patients about what to expect from an exercise program, be it supervised or home based.
“It’s not like revascularization, where they’re going to feel better in their walking immediately. It really takes a commitment. Four to six weeks is usually required before patients begin to experience a benefit, and I think it’s really important for patients to know that so they don’t get discouraged in the first couple of weeks,” Dr. McDermott said.
Turning to the key evidence-based behavioral change techniques shared by successful home-exercise programs for PAD, she noted that the GOALS trial intervention utilized weekly group sessions in which simple cognitive behavioral self-regulatory techniques were used to help patients set and stick to home-based walking goals. A similarly positive randomized controlled trial by investigators at the University of Oklahoma utilized once-monthly group meetings at the medical center (J Am Heart Assoc. 2014 Sep 18;3(5):e001107. doi: 10.1161/JAHA.114.001107).
In contrast, in the recent HONOR randomized clinical trial, where Dr. McDermott and her coinvestigators tested whether a home-based exercise intervention in which the active treatment group utilized a Fitbit wearable activity monitor and telephone coaching over the course of 9 months, the results proved disappointing. The intervention was no more effective than was usual care at improving 6MWD (JAMA. 2018 Apr 24;319(16):1665-76).
“One of the things I learned from doing this trial is that for a home-based exercise intervention in PAD to be successful, it’s not easy and there really needs to be some ongoing contact with a coach or nurse or a staff member that the patient feels accountable to. A wearable device is not a durably effective motivator for PAD patients. I think the reason this trial didn’t work so well is that most of it was by telephone and it was easy for patients to avoid our calls if they weren’t walking. Patients were initially really enthusiastic about the Fitbit, but we found that over time they stopped wearing it,” she said.
Dr. McDermott heartily endorses the Society for Vascular Surgery’s Class I recommendation that all PAD patients with intermittent claudication should exercise regularly, including those who’ve undergone revascularization procedures. Numerous clinical trials have demonstrated additive clinical benefits for opening the peripheral artery and strengthening skeletal muscles.
Uptake of supervised exercise programs for symptomatic PAD since the CMS coverage decision is quite variable regionally. Integrating new programs into existing cardiac rehabilitation facilities is a natural fit because staff members are very familiar with structured treadmill exercises already on site, but some freestanding programs are run by vascular surgery groups or cardiologists.
“I think part of the reason it hasn’t been taken up faster is that the reimbursement is such that you’re not going to make money on it,” Dr. McDermott said.
Asked if all patients with PAD should undergo an exercise treadmill test before embarking on an exercise program, Dr. McDermott replied, “I’m part of a writing group for the American Heart Association on how to implement these new guidelines. We’re not formally recommending a stress test. Some cardiologists on the panel suggested that it should be individualized based on patient history and symptoms. If they’re having symptoms of chest pain or they have a significant cardiac history, go ahead with a stress test. I don’t think it’s going to be recommended as a routine practice, but it’s safest to get a stress test.”
She reported having no financial conflicts regarding her presentation.
Requirements for CMS coverage of supervised exercise for symptomatic PAD
*The exercise program must consist of 12 weeks of thrice-weekly sessions.
*It has to be prescribed by a physician following a face-to-face meeting with the patient during which the physician provides education on cardiovascular risk prevention.
*An additional 36 sessions of supervised exercise can be obtained with a written note of justification by the physician following completion of the initial 12 weeks.
*The sessions must take place in a physician’s office or an outpatient hospital setting.
*The exercise has to be supervised by a physician, physician assistant, or nurse specialist.
*The exercise must be delivered by qualified personnel trained in basic and advanced cardiac life support as well as exercise therapy for PAD.
CHICAGO – Home-based exercise for peripheral arterial disease–related walking limitations works at least as well as – and arguably better than – the supervised outpatient hospital clinic-based treadmill exercise programs of the type approved for coverage by the Centers for Medicare and Medicaid Services in 2017, Mary M. McDermott, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
“The prevailing thinking is that supervised treadmill exercise is more effective than home-based exercise for PAD. And for the outcome of treadmill walking that is true. But for the outcome of 6-minute walking distance, which I would argue is more relevant to walking in daily life, home-based exercise programs appear to be better. Supervised treadmill exercise interventions preferentially improve treadmill walking performance, and that doesn’t translate as well to walking in daily life. Home-based exercise, where patients walk in a corridor or on the ground, is more relevant to the type of walking that they want to do,” explained Dr. McDermott, professor of medicine at the university as well as a leader in the field of research on exercise as a treatment for PAD.
However, she added a caveat regarding home-based exercise for symptomatic PAD: For it to be effective it must incorporate proven behavioral change techniques, including goal setting, monitoring progress, accountability to a coach, and face-to-face visits at least once per month.
“It seems you can’t just tell PAD patients to go home and walk because most of them won’t do it,” observed Dr. McDermott, who is a general internist and geriatrician.
Home-based exercise programs aren’t reimbursed by the CMS. But studies by Dr. McDermott and other investigators indicate that the results are more durable than for supervised treadmill exercise. For example, in the Group Oriented Arterial Leg Study (GOALS) – a 6-month group-mediated cognitive behavioral intervention in which PAD patients built up to walking at home for up to 50 minutes per session 5 days per week – 6-minute walking distance (6MWD) remained significantly better than in controls at follow-up after completion of the intervention. In fact, 6MWD actually increased further between 6 and 12 months in the home exercise group (J Am Heart Assoc. 2014 May 21;3(3):e000711. doi: 10.1161/JAHA.113.000711). Dr. McDermott was the lead author for this study.
In contrast, another study by Dr. McDermott now in press for the same journal found that the improvement in 6MWD achieved in PAD patients over the course of a 6-month supervised treadmill exercise program was not maintained during the next 6 months after completion of the intervention. Indeed, 6MWD showed a steady decline from its apex at the intervention’s conclusion, such that at the 12-month mark it was no longer significantly different from that of the control group, according to Dr. McDermott.
The Society for Vascular Surgery recommends a supervised exercise program as first-line therapy for PAD patients with intermittent claudication, with a Class I Level of Evidence A designation. Home-based exercise also gets a Class I recommendation, albeit with Level of Evidence B.
Dr. McDermott believes a home exercise program makes the most sense for PAD patients after their CMS benefit for a supervised clinic-based program has run out, or for patients – and there are a great many – who either can’t or don’t want to participate in a supervised program. She and others who’ve led randomized controlled trials of supervised exercise programs have found that close to 70% of eligible PAD patients decline to participate because of the inconvenience of going to the hospital outpatient facility at least three times per week or for other reasons.
“Also, it’s important to recognize that attendance can be a challenge, even when supervised exercise is covered by insurance. In our randomized trials, where we provide transportation, we still see only 65%-70% adherence to attendance,” she noted.
She stressed that it’s crucial for physicians and surgeons to educate their PAD patients about what to expect from an exercise program, be it supervised or home based.
“It’s not like revascularization, where they’re going to feel better in their walking immediately. It really takes a commitment. Four to six weeks is usually required before patients begin to experience a benefit, and I think it’s really important for patients to know that so they don’t get discouraged in the first couple of weeks,” Dr. McDermott said.
Turning to the key evidence-based behavioral change techniques shared by successful home-exercise programs for PAD, she noted that the GOALS trial intervention utilized weekly group sessions in which simple cognitive behavioral self-regulatory techniques were used to help patients set and stick to home-based walking goals. A similarly positive randomized controlled trial by investigators at the University of Oklahoma utilized once-monthly group meetings at the medical center (J Am Heart Assoc. 2014 Sep 18;3(5):e001107. doi: 10.1161/JAHA.114.001107).
In contrast, in the recent HONOR randomized clinical trial, where Dr. McDermott and her coinvestigators tested whether a home-based exercise intervention in which the active treatment group utilized a Fitbit wearable activity monitor and telephone coaching over the course of 9 months, the results proved disappointing. The intervention was no more effective than was usual care at improving 6MWD (JAMA. 2018 Apr 24;319(16):1665-76).
“One of the things I learned from doing this trial is that for a home-based exercise intervention in PAD to be successful, it’s not easy and there really needs to be some ongoing contact with a coach or nurse or a staff member that the patient feels accountable to. A wearable device is not a durably effective motivator for PAD patients. I think the reason this trial didn’t work so well is that most of it was by telephone and it was easy for patients to avoid our calls if they weren’t walking. Patients were initially really enthusiastic about the Fitbit, but we found that over time they stopped wearing it,” she said.
Dr. McDermott heartily endorses the Society for Vascular Surgery’s Class I recommendation that all PAD patients with intermittent claudication should exercise regularly, including those who’ve undergone revascularization procedures. Numerous clinical trials have demonstrated additive clinical benefits for opening the peripheral artery and strengthening skeletal muscles.
Uptake of supervised exercise programs for symptomatic PAD since the CMS coverage decision is quite variable regionally. Integrating new programs into existing cardiac rehabilitation facilities is a natural fit because staff members are very familiar with structured treadmill exercises already on site, but some freestanding programs are run by vascular surgery groups or cardiologists.
“I think part of the reason it hasn’t been taken up faster is that the reimbursement is such that you’re not going to make money on it,” Dr. McDermott said.
Asked if all patients with PAD should undergo an exercise treadmill test before embarking on an exercise program, Dr. McDermott replied, “I’m part of a writing group for the American Heart Association on how to implement these new guidelines. We’re not formally recommending a stress test. Some cardiologists on the panel suggested that it should be individualized based on patient history and symptoms. If they’re having symptoms of chest pain or they have a significant cardiac history, go ahead with a stress test. I don’t think it’s going to be recommended as a routine practice, but it’s safest to get a stress test.”
She reported having no financial conflicts regarding her presentation.
Requirements for CMS coverage of supervised exercise for symptomatic PAD
*The exercise program must consist of 12 weeks of thrice-weekly sessions.
*It has to be prescribed by a physician following a face-to-face meeting with the patient during which the physician provides education on cardiovascular risk prevention.
*An additional 36 sessions of supervised exercise can be obtained with a written note of justification by the physician following completion of the initial 12 weeks.
*The sessions must take place in a physician’s office or an outpatient hospital setting.
*The exercise has to be supervised by a physician, physician assistant, or nurse specialist.
*The exercise must be delivered by qualified personnel trained in basic and advanced cardiac life support as well as exercise therapy for PAD.
REPORTING FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
CABG surpasses PCI for diabetics out to 7.5 years
CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.
Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.
Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).
The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.
Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).
The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.
Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.
FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.
SOURCE: Fuster V et al. AHA 2018, Abstract 18609.
These extended results from the FREEDOM trial that followed many patients for 10 years or longer add to the consistent evidence base that supports coronary artery bypass grafting (CABG) as the preferred revascularization strategy for patients with diabetes and multivessel coronary disease. The new findings support existing society guidelines that recommend CABG over percutaneous coronary intervention in these patients, most recently in the revascularization guidelines from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394). An update to the U.S. guidelines should appear in 2019.
Continued improvement of revascularization techniques, hardware, and medical management of patients with diabetes and multivessel coronary artery disease makes it challenging to apply the results of studies run in earlier eras to today’s practice. It is possible that continued evolution of coronary stent technology may reduce the differences in outcomes between bypass surgery and percutaneous coronary interventions, although this is less likely if much of CABG’s success relates to the protection it gives against new disease. Future comparisons of different approaches with revascularization will need to take into account the potential contribution of other procedures, other adverse outcomes aside from mortality during long-term follow-up, the consequences of incomplete revascularization, and the impact of new medications for treating diabetes that have been recently shown to also have cardiovascular disease effects. All these factors in concert will define the optimal approach to managing these patients.
Alice K. Jacobs, MD , is director of the cardiac catheterization laboratory at Boston Medical Center and a professor of medicine at Boston University. She has received research support from Abbott Vascular. She made these comments as designated discussant for the study.
These extended results from the FREEDOM trial that followed many patients for 10 years or longer add to the consistent evidence base that supports coronary artery bypass grafting (CABG) as the preferred revascularization strategy for patients with diabetes and multivessel coronary disease. The new findings support existing society guidelines that recommend CABG over percutaneous coronary intervention in these patients, most recently in the revascularization guidelines from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394). An update to the U.S. guidelines should appear in 2019.
Continued improvement of revascularization techniques, hardware, and medical management of patients with diabetes and multivessel coronary artery disease makes it challenging to apply the results of studies run in earlier eras to today’s practice. It is possible that continued evolution of coronary stent technology may reduce the differences in outcomes between bypass surgery and percutaneous coronary interventions, although this is less likely if much of CABG’s success relates to the protection it gives against new disease. Future comparisons of different approaches with revascularization will need to take into account the potential contribution of other procedures, other adverse outcomes aside from mortality during long-term follow-up, the consequences of incomplete revascularization, and the impact of new medications for treating diabetes that have been recently shown to also have cardiovascular disease effects. All these factors in concert will define the optimal approach to managing these patients.
Alice K. Jacobs, MD , is director of the cardiac catheterization laboratory at Boston Medical Center and a professor of medicine at Boston University. She has received research support from Abbott Vascular. She made these comments as designated discussant for the study.
These extended results from the FREEDOM trial that followed many patients for 10 years or longer add to the consistent evidence base that supports coronary artery bypass grafting (CABG) as the preferred revascularization strategy for patients with diabetes and multivessel coronary disease. The new findings support existing society guidelines that recommend CABG over percutaneous coronary intervention in these patients, most recently in the revascularization guidelines from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394). An update to the U.S. guidelines should appear in 2019.
Continued improvement of revascularization techniques, hardware, and medical management of patients with diabetes and multivessel coronary artery disease makes it challenging to apply the results of studies run in earlier eras to today’s practice. It is possible that continued evolution of coronary stent technology may reduce the differences in outcomes between bypass surgery and percutaneous coronary interventions, although this is less likely if much of CABG’s success relates to the protection it gives against new disease. Future comparisons of different approaches with revascularization will need to take into account the potential contribution of other procedures, other adverse outcomes aside from mortality during long-term follow-up, the consequences of incomplete revascularization, and the impact of new medications for treating diabetes that have been recently shown to also have cardiovascular disease effects. All these factors in concert will define the optimal approach to managing these patients.
Alice K. Jacobs, MD , is director of the cardiac catheterization laboratory at Boston Medical Center and a professor of medicine at Boston University. She has received research support from Abbott Vascular. She made these comments as designated discussant for the study.
CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.
Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.
Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).
The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.
Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).
The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.
Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.
FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.
SOURCE: Fuster V et al. AHA 2018, Abstract 18609.
CHICAGO – Patients with diabetes who underwent coronary artery bypass grafting had significantly better survival than patients with diabetes who underwent percutaneous coronary intervention after a median 7.5 years of follow-up.
Those patients comprised about half the patients enrolled in the FREEDOM randomized trial.
Long-term follow-up was only possible for just under half the 1,900 patients with diabetes and multivessel coronary disease originally enrolled in FREEDOM, but when researchers combined the long-term results with the data collected in the original study that had a median 3.8-year follow-up, they found all-cause mortality occurred in 18.3% of the patients who underwent coronary artery bypass grafting (CABG) and in 24.3% of patients treated with percutaneous coronary intervention (PCI), a 6% absolute between-group difference that was statistically significant, Valentin Fuster, MD, said at the American Heart Association scientific sessions. This fully jibed with the primary FREEDOM results, which found after 5 years a statistically significant reduction in all-cause death with CABG, compared with PCI, and also a significant reduction in the study’s primary endpoint (a combination of all-cause death, MI, and stroke), which occurred in 18.7% of patients randomized to CABG and in 26.6% of those randomized to PCI (N Engl J Med. 2012 Dec 20;367[25]:2375-84).
The extended follow-up finding lent additional support to existing society recommendations that CABG is the preferred revascularization strategy for patients with diabetes and multivessel coronary disease, most recently from the European Society of Cardiology (Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394), said Dr. Fuster, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of Mount Sinai Heart in New York. A subgroup analysis of the extended follow-up also suggested that the survival benefit from CABG, compared with PCI, was especially strong among patients at or below the study’s median age of 63 years. In the younger subgroup survival among patients treated with CABG was twice as good as it was among patients treated with PCI.
Dr. Fuster noted that few data have been previously reported for survival rates beyond 5 years after revascularization. “This was a difficult study. Following patients for more than 5 years is hard,” he said. Concurrently with his report at the meeting the results also appeared online (J Am Coll Cardiol. 2018 Nov 11. doi: 10.1016/j.jacc.2018.11.001).
The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial enrolled patients at 140 participating centers during 2005-2010. A total of 25 sites agreed to participate in the extended follow-up and could track 943 patients, 50% of the starting cohort of 1,900 and 89% of the patients originally enrolled at these 25 centers. Dr. Fuster stressed that the 957 patients not included in the follow-up had not been lost, but rather had been managed at sites that declined to participate in this additional study.
Dr. Fuster acknowledged that methods and hardware for PCI have changed since the study ran a decade ago, as have options for medical management. He also highlighted that the long-term follow-up results had no data on rates of MIs and strokes.
FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.
SOURCE: Fuster V et al. AHA 2018, Abstract 18609.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: After 7.5 years, mortality in the full FREEDOM cohort was 18% after coronary artery bypass grafting and 24% after percutaneous coronary intervention.
Study details: An extended follow-up of 943 of patients enrolled in FREEDOM, a randomized, multicenter trial.
Disclosures: FREEDOM had no commercial funding. Dr. Fuster reported no relevant disclosures.
Source: Fuster V et al. AHA 2018, Abstract 18609.
Partial- and whole-breast irradiation very close in efficacy
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
REPORTING FROM SABCS 2018
Key clinical point: Partial- and whole-breast irradiation yield outcomes that are statistically nonequivalent but very similar.
Major finding: The hazard ratio for ipsilateral recurrences with partial- vs. whole-breast irradiation was 1.22, with the confidence interval falling just outside the range for equivalence, but the absolute difference in 10-year rate was just 0.7% (4.6% vs. 3.9%).
Study details: A phase 3, randomized, controlled trial among women who underwent lumpectomy for stage 0-II breast cancer, conducted by NRG Oncology (NSABP B-39/RTOG 0413).
Disclosures: Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
Source: Vicini FA et al. SABCS 2018, Abstract GS4-04.
Brain injury in sickle cell merits more attention
BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.
“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.
The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).
One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.
“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”
Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).
But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.
Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.
While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.
“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”
Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.
BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.
“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.
The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).
One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.
“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”
Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).
But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.
Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.
While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.
“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”
Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.
BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.
“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.
The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).
One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.
“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”
Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).
But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.
Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.
While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.
“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”
Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.
EXPERT ANALYSIS FROM SICKLE CELL IN FOCUS
No matter the valve, protective device cuts post-TAVR stroke risk
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
REPORTING FROM TCT 2018
What is your diagnosis?
Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.
There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.
EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.
There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA1. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers2.
The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome3. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction
Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].
References
1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.
2. J Med Genet. 2010 Dec;47(12):859-62.
3. Pediatr Dermatol. 2018 Jan;35(1):21-9.
Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.
There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.
EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.
There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA1. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers2.
The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome3. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction
Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].
References
1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.
2. J Med Genet. 2010 Dec;47(12):859-62.
3. Pediatr Dermatol. 2018 Jan;35(1):21-9.
Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.
There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.
EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.
There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA1. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers2.
The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome3. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction
Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].
References
1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.
2. J Med Genet. 2010 Dec;47(12):859-62.
3. Pediatr Dermatol. 2018 Jan;35(1):21-9.
A 6-year-old, otherwise-healthy male is brought into clinic for evaluation of papules on his neck. The rash has been present since 1 year of age and has been growing in size proportionately. He claims there is occasional itching but no pain or redness. He does not seem to be disturbed by his rash. He has two siblings, aged 2 and 4 years, without lesions.
On physical exam, he is noted to have a linear plaque of hyperpigmented verrucous papules on his neck.