ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

A minority of patients (43.5%) with an indication for breast cancer genetic risk evaluation actually received formal genetic counseling in clinical practice, according to an analysis of NCI Surveillance, Epidemiology, and End Results (SEER) data published in Journal of Clinical Oncology.

More expertise is required in genetic counseling, either formal counseling given by an expert, or by a cancer physician (physician-directed), wrote Steven J. Katz and his colleagues at the University of Michigan, Ann Arbor. With BRCA1/2-only testing, being replaced by multi-gene panel testing, further consideration and/or discussion of results and formulation of a management plan is required, they said.

In addition, younger women more often reported some type of counseling (odds ratio, 4.5;95% confidence interval, 2.6-8.0; 1.9;95% CI, 1.1-3.3; and 1.5;95% CI, 1.0-2.3 for women younger than 50 years of age, 50-59 years of age, and 60-69 years of age, respectively, versus those 70 years of age and older).

Patients’ assessment of the amount of information they received about whether to have testing was high, “whether they received formal genetic counseling or a physician-directed discussion only (80.8% v 79.4% stated information was ‘just right’; P = .58),” the researchers noted.

As high-throughput molecular testing becomes increasingly complex, personalizing and tailoring the information to a individual patients’ need is crucial, the authors said. They further suggest a multipronged strategy that will train oncologists to integrate genetic testing into clinical decision making; including timely testing of patients at an elevated risk.

The study was supported by Grant P01 CA163233 to the University of Michigan from the National Cancer Institute. Potential conflict of interests were reported by Lauren P. Wallner, PhD (GlaxoSmithKline); Monica Morrow, MD (Genomic Health); Reshma Jagsi, MD (Amgen and AbbVie); and Allison W. Kurian, MD (Myriad Genetics, Invitae, Ambry Genetics, Genomic Health, GeneDx/BioReference, Genentech (a member of the Roche Group).

SOURCE: Katz SJ et al. J Clin Oncol. 2018 Mar 12. doi: 10.1200/JCO.2017.76.2369.

A minority of patients (43.5%) with an indication for breast cancer genetic risk evaluation actually received formal genetic counseling in clinical practice, according to an analysis of NCI Surveillance, Epidemiology, and End Results (SEER) data published in Journal of Clinical Oncology.

More expertise is required in genetic counseling, either formal counseling given by an expert, or by a cancer physician (physician-directed), wrote Steven J. Katz and his colleagues at the University of Michigan, Ann Arbor. With BRCA1/2-only testing, being replaced by multi-gene panel testing, further consideration and/or discussion of results and formulation of a management plan is required, they said.

In addition, younger women more often reported some type of counseling (odds ratio, 4.5;95% confidence interval, 2.6-8.0; 1.9;95% CI, 1.1-3.3; and 1.5;95% CI, 1.0-2.3 for women younger than 50 years of age, 50-59 years of age, and 60-69 years of age, respectively, versus those 70 years of age and older).

Patients’ assessment of the amount of information they received about whether to have testing was high, “whether they received formal genetic counseling or a physician-directed discussion only (80.8% v 79.4% stated information was ‘just right’; P = .58),” the researchers noted.

As high-throughput molecular testing becomes increasingly complex, personalizing and tailoring the information to a individual patients’ need is crucial, the authors said. They further suggest a multipronged strategy that will train oncologists to integrate genetic testing into clinical decision making; including timely testing of patients at an elevated risk.

The study was supported by Grant P01 CA163233 to the University of Michigan from the National Cancer Institute. Potential conflict of interests were reported by Lauren P. Wallner, PhD (GlaxoSmithKline); Monica Morrow, MD (Genomic Health); Reshma Jagsi, MD (Amgen and AbbVie); and Allison W. Kurian, MD (Myriad Genetics, Invitae, Ambry Genetics, Genomic Health, GeneDx/BioReference, Genentech (a member of the Roche Group).

SOURCE: Katz SJ et al. J Clin Oncol. 2018 Mar 12. doi: 10.1200/JCO.2017.76.2369.

A minority of patients (43.5%) with an indication for breast cancer genetic risk evaluation actually received formal genetic counseling in clinical practice, according to an analysis of NCI Surveillance, Epidemiology, and End Results (SEER) data published in Journal of Clinical Oncology.

More expertise is required in genetic counseling, either formal counseling given by an expert, or by a cancer physician (physician-directed), wrote Steven J. Katz and his colleagues at the University of Michigan, Ann Arbor. With BRCA1/2-only testing, being replaced by multi-gene panel testing, further consideration and/or discussion of results and formulation of a management plan is required, they said.

In addition, younger women more often reported some type of counseling (odds ratio, 4.5;95% confidence interval, 2.6-8.0; 1.9;95% CI, 1.1-3.3; and 1.5;95% CI, 1.0-2.3 for women younger than 50 years of age, 50-59 years of age, and 60-69 years of age, respectively, versus those 70 years of age and older).

Patients’ assessment of the amount of information they received about whether to have testing was high, “whether they received formal genetic counseling or a physician-directed discussion only (80.8% v 79.4% stated information was ‘just right’; P = .58),” the researchers noted.

As high-throughput molecular testing becomes increasingly complex, personalizing and tailoring the information to a individual patients’ need is crucial, the authors said. They further suggest a multipronged strategy that will train oncologists to integrate genetic testing into clinical decision making; including timely testing of patients at an elevated risk.

The study was supported by Grant P01 CA163233 to the University of Michigan from the National Cancer Institute. Potential conflict of interests were reported by Lauren P. Wallner, PhD (GlaxoSmithKline); Monica Morrow, MD (Genomic Health); Reshma Jagsi, MD (Amgen and AbbVie); and Allison W. Kurian, MD (Myriad Genetics, Invitae, Ambry Genetics, Genomic Health, GeneDx/BioReference, Genentech (a member of the Roche Group).

SOURCE: Katz SJ et al. J Clin Oncol. 2018 Mar 12. doi: 10.1200/JCO.2017.76.2369.

Investigational agent fruquintinib holds promise as a third- or fourth-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC), according to new findings published in the Journal of Clinical Oncology.

The median progression free survival (PFS) as evaluated by a blinded image central review committee and the study’s primary endpoint, was more than threefold higher than observed with placebo; 3.8 months (95% confidence interval, 2.8 to 4.6 months) with fruquintinib versus 1.1 months (95% CI, 1.0 to 1.9 months) with placebo (stratified HR was 0.34 (95% CI,0.20 to 0.57; P less than .001). PFS assessed by investigators was nearly identical.

Median overall survival, however, was numerically longer for patients in the placebo arm versus the fruquintinib arm (7.7 and 9.7 months in the fruquintinib and placebo groups; stratified HR, 0.70; 95% CI, 0.43 to 1.15; P = .152). The authors point out that overall survival is a secondary endpoint and the study was insufficiently powered to assess differences in overall survival.

“In patients with NSCLC who experienced treatment failure with two standard chemotherapies, fruquintinib may provide a clinically meaningful benefit, and further evidence of a statistically significant OS benefit of fruquintinib is expected from a phase 3 randomized study in this target population,” wrote Dr. Shun Lu of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China, and colleagues.

Fruquintinib is a highly selective inhibitor of VEGFR-1, -2 and -3 kinases, and showed promising activity against solid tumors, including NSCLC, in a phase 1 trial. The current phase 2 trial evaluated the efficacy and safety of single-agent fruquintinib in 91 patients with advanced nonsquamous NSCLC. All patients had experienced disease progression after two lines of standard chemotherapy, and were randomly assigned to be treated with either fruquintinib (n = 61) or placebo (n = 30).

At data cutoff for PFS analysis, a total of 46 patients (75.4%) in the fruquintinib group and 25 (83.3%) in the placebo group had experienced a PFS event. The median follow-up for survival was 28.0 months for fruquintinib and 25.4 months for the placebo group.

Both the 3- and 6-month survival rates were numerically higher for patients receiving fruquintinib group versus placebo (90.2% vs. 73.3% for 3-month survival and 67.2% vs. 58.8% for 6-month survival).

The results for other secondary endpoints showed a more favorable overall response rate for fruquintinib vs placebo (13.1% vs 0%; P = .041), as was the disease control rate (60.7% vs 13.3%; P less than .001).

Subgroup analyses favored PFS with fruquintinib, as it was significantly longer vs. placebo for all patient subsets except for those with brain metastases. The median overall survival also was numerically greater with fruquintinib among patients positive for EGFR mutations (8.4 vs. 5.5 months; HR, 0.58; 95% CI, 0.30-1.141 P =.11).

Treatment emergent adverse events were higher in the fruquintinib arm (100% vs. 90%), but most of these were grade 1/2 in both groups. The most common grade 3 and higher events observed with fruquintinib were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%).

SOURCE: Lu S. et al. J Clin Oncol. 2018 Mar. 12 doi: 10.1200/JCO.2017.76.7145.

Investigational agent fruquintinib holds promise as a third- or fourth-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC), according to new findings published in the Journal of Clinical Oncology.

The median progression free survival (PFS) as evaluated by a blinded image central review committee and the study’s primary endpoint, was more than threefold higher than observed with placebo; 3.8 months (95% confidence interval, 2.8 to 4.6 months) with fruquintinib versus 1.1 months (95% CI, 1.0 to 1.9 months) with placebo (stratified HR was 0.34 (95% CI,0.20 to 0.57; P less than .001). PFS assessed by investigators was nearly identical.

Median overall survival, however, was numerically longer for patients in the placebo arm versus the fruquintinib arm (7.7 and 9.7 months in the fruquintinib and placebo groups; stratified HR, 0.70; 95% CI, 0.43 to 1.15; P = .152). The authors point out that overall survival is a secondary endpoint and the study was insufficiently powered to assess differences in overall survival.

“In patients with NSCLC who experienced treatment failure with two standard chemotherapies, fruquintinib may provide a clinically meaningful benefit, and further evidence of a statistically significant OS benefit of fruquintinib is expected from a phase 3 randomized study in this target population,” wrote Dr. Shun Lu of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China, and colleagues.

Fruquintinib is a highly selective inhibitor of VEGFR-1, -2 and -3 kinases, and showed promising activity against solid tumors, including NSCLC, in a phase 1 trial. The current phase 2 trial evaluated the efficacy and safety of single-agent fruquintinib in 91 patients with advanced nonsquamous NSCLC. All patients had experienced disease progression after two lines of standard chemotherapy, and were randomly assigned to be treated with either fruquintinib (n = 61) or placebo (n = 30).

At data cutoff for PFS analysis, a total of 46 patients (75.4%) in the fruquintinib group and 25 (83.3%) in the placebo group had experienced a PFS event. The median follow-up for survival was 28.0 months for fruquintinib and 25.4 months for the placebo group.

Both the 3- and 6-month survival rates were numerically higher for patients receiving fruquintinib group versus placebo (90.2% vs. 73.3% for 3-month survival and 67.2% vs. 58.8% for 6-month survival).

The results for other secondary endpoints showed a more favorable overall response rate for fruquintinib vs placebo (13.1% vs 0%; P = .041), as was the disease control rate (60.7% vs 13.3%; P less than .001).

Subgroup analyses favored PFS with fruquintinib, as it was significantly longer vs. placebo for all patient subsets except for those with brain metastases. The median overall survival also was numerically greater with fruquintinib among patients positive for EGFR mutations (8.4 vs. 5.5 months; HR, 0.58; 95% CI, 0.30-1.141 P =.11).

Treatment emergent adverse events were higher in the fruquintinib arm (100% vs. 90%), but most of these were grade 1/2 in both groups. The most common grade 3 and higher events observed with fruquintinib were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%).

SOURCE: Lu S. et al. J Clin Oncol. 2018 Mar. 12 doi: 10.1200/JCO.2017.76.7145.

Investigational agent fruquintinib holds promise as a third- or fourth-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC), according to new findings published in the Journal of Clinical Oncology.

The median progression free survival (PFS) as evaluated by a blinded image central review committee and the study’s primary endpoint, was more than threefold higher than observed with placebo; 3.8 months (95% confidence interval, 2.8 to 4.6 months) with fruquintinib versus 1.1 months (95% CI, 1.0 to 1.9 months) with placebo (stratified HR was 0.34 (95% CI,0.20 to 0.57; P less than .001). PFS assessed by investigators was nearly identical.

Median overall survival, however, was numerically longer for patients in the placebo arm versus the fruquintinib arm (7.7 and 9.7 months in the fruquintinib and placebo groups; stratified HR, 0.70; 95% CI, 0.43 to 1.15; P = .152). The authors point out that overall survival is a secondary endpoint and the study was insufficiently powered to assess differences in overall survival.

“In patients with NSCLC who experienced treatment failure with two standard chemotherapies, fruquintinib may provide a clinically meaningful benefit, and further evidence of a statistically significant OS benefit of fruquintinib is expected from a phase 3 randomized study in this target population,” wrote Dr. Shun Lu of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China, and colleagues.

Fruquintinib is a highly selective inhibitor of VEGFR-1, -2 and -3 kinases, and showed promising activity against solid tumors, including NSCLC, in a phase 1 trial. The current phase 2 trial evaluated the efficacy and safety of single-agent fruquintinib in 91 patients with advanced nonsquamous NSCLC. All patients had experienced disease progression after two lines of standard chemotherapy, and were randomly assigned to be treated with either fruquintinib (n = 61) or placebo (n = 30).

At data cutoff for PFS analysis, a total of 46 patients (75.4%) in the fruquintinib group and 25 (83.3%) in the placebo group had experienced a PFS event. The median follow-up for survival was 28.0 months for fruquintinib and 25.4 months for the placebo group.

Both the 3- and 6-month survival rates were numerically higher for patients receiving fruquintinib group versus placebo (90.2% vs. 73.3% for 3-month survival and 67.2% vs. 58.8% for 6-month survival).

The results for other secondary endpoints showed a more favorable overall response rate for fruquintinib vs placebo (13.1% vs 0%; P = .041), as was the disease control rate (60.7% vs 13.3%; P less than .001).

Subgroup analyses favored PFS with fruquintinib, as it was significantly longer vs. placebo for all patient subsets except for those with brain metastases. The median overall survival also was numerically greater with fruquintinib among patients positive for EGFR mutations (8.4 vs. 5.5 months; HR, 0.58; 95% CI, 0.30-1.141 P =.11).

Treatment emergent adverse events were higher in the fruquintinib arm (100% vs. 90%), but most of these were grade 1/2 in both groups. The most common grade 3 and higher events observed with fruquintinib were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%).

SOURCE: Lu S. et al. J Clin Oncol. 2018 Mar. 12 doi: 10.1200/JCO.2017.76.7145.

ORLANDO – Using videoconferencing to assess patients for a reported penicillin allergy saved more than 2 hours of physician time for every patient, and resulted in almost every patient having their allergy label removed, researchers reported.

In what the researchers said was the first study showing the utility of telemedicine in evaluating patient-reported penicillin allergies, allergy and immunology physicians did a secure telemedicine consultation with patients after they underwent penicillin skin testing with a physician assistant; an approach which, on average, took 123 minutes fewer each time than if the physician had done the consultation face-to-face. The teleconference can be done on a laptop or smartphone.

Thomas R. Collins/Frontline Medical Communications

“This is so overlabeled,” Dr. Ramsey said. “Ten percent of the population thinks they’re allergic to penicillin, and 90% of them are not.”

A stark difference was found in the types of medicines administered before and after the evaluations, with aminopenicillin therapy jumping from 0 days of use to 188 days, and vancomycin – a more potent, but more costly alternative – dropping from 130 days of use to 16 days (P less than .05 for both).

Dr. Ramsey noted that, in part because of the time-consuming nature of the penicillin skin tests, they often are simply not done, so the false allergy labels are not caught, leading to pointless costs and exposure to more potent and potentially harmful forms of antibiotic therapy.

“Some hospitals don’t have allergists who will come in to do testing,” she said. “Sometimes patients are on medications that may interfere. And then a lot of times it’s just underrecognized – the implications of a penicillin allergy label. That is a very hot topic in our field and also in infectious disease.”

She hopes the telemedicine approach catches on more widely, which would help minimize the multitude of problems linked to penicillin allergy labels.

“Patients that avoid penicillin, they’re on more costly second-line antibiotics that are, in general, less effective, depending on which infection you’re talking about,” Dr. Ramsey said. “The [second-line antibiotics] have more side effects. And there’s data to show that patients with [a] penicillin allergy label have longer hospital stays, more costly hospital stays, are at risk for more resistant infections. And it breeds antimicrobial resistance in the long-term.”

Dr. Ramsey had no relevant financial disclosures.

SOURCE: Ramsey AC et al. AAAAI/WAO Joint Congress, Abstract 104.

ORLANDO – Using videoconferencing to assess patients for a reported penicillin allergy saved more than 2 hours of physician time for every patient, and resulted in almost every patient having their allergy label removed, researchers reported.

In what the researchers said was the first study showing the utility of telemedicine in evaluating patient-reported penicillin allergies, allergy and immunology physicians did a secure telemedicine consultation with patients after they underwent penicillin skin testing with a physician assistant; an approach which, on average, took 123 minutes fewer each time than if the physician had done the consultation face-to-face. The teleconference can be done on a laptop or smartphone.

Thomas R. Collins/Frontline Medical Communications

“This is so overlabeled,” Dr. Ramsey said. “Ten percent of the population thinks they’re allergic to penicillin, and 90% of them are not.”

A stark difference was found in the types of medicines administered before and after the evaluations, with aminopenicillin therapy jumping from 0 days of use to 188 days, and vancomycin – a more potent, but more costly alternative – dropping from 130 days of use to 16 days (P less than .05 for both).

Dr. Ramsey noted that, in part because of the time-consuming nature of the penicillin skin tests, they often are simply not done, so the false allergy labels are not caught, leading to pointless costs and exposure to more potent and potentially harmful forms of antibiotic therapy.

“Some hospitals don’t have allergists who will come in to do testing,” she said. “Sometimes patients are on medications that may interfere. And then a lot of times it’s just underrecognized – the implications of a penicillin allergy label. That is a very hot topic in our field and also in infectious disease.”

She hopes the telemedicine approach catches on more widely, which would help minimize the multitude of problems linked to penicillin allergy labels.

“Patients that avoid penicillin, they’re on more costly second-line antibiotics that are, in general, less effective, depending on which infection you’re talking about,” Dr. Ramsey said. “The [second-line antibiotics] have more side effects. And there’s data to show that patients with [a] penicillin allergy label have longer hospital stays, more costly hospital stays, are at risk for more resistant infections. And it breeds antimicrobial resistance in the long-term.”

Dr. Ramsey had no relevant financial disclosures.

SOURCE: Ramsey AC et al. AAAAI/WAO Joint Congress, Abstract 104.

ORLANDO – Using videoconferencing to assess patients for a reported penicillin allergy saved more than 2 hours of physician time for every patient, and resulted in almost every patient having their allergy label removed, researchers reported.

In what the researchers said was the first study showing the utility of telemedicine in evaluating patient-reported penicillin allergies, allergy and immunology physicians did a secure telemedicine consultation with patients after they underwent penicillin skin testing with a physician assistant; an approach which, on average, took 123 minutes fewer each time than if the physician had done the consultation face-to-face. The teleconference can be done on a laptop or smartphone.

Thomas R. Collins/Frontline Medical Communications

“This is so overlabeled,” Dr. Ramsey said. “Ten percent of the population thinks they’re allergic to penicillin, and 90% of them are not.”

A stark difference was found in the types of medicines administered before and after the evaluations, with aminopenicillin therapy jumping from 0 days of use to 188 days, and vancomycin – a more potent, but more costly alternative – dropping from 130 days of use to 16 days (P less than .05 for both).

Dr. Ramsey noted that, in part because of the time-consuming nature of the penicillin skin tests, they often are simply not done, so the false allergy labels are not caught, leading to pointless costs and exposure to more potent and potentially harmful forms of antibiotic therapy.

“Some hospitals don’t have allergists who will come in to do testing,” she said. “Sometimes patients are on medications that may interfere. And then a lot of times it’s just underrecognized – the implications of a penicillin allergy label. That is a very hot topic in our field and also in infectious disease.”

She hopes the telemedicine approach catches on more widely, which would help minimize the multitude of problems linked to penicillin allergy labels.

“Patients that avoid penicillin, they’re on more costly second-line antibiotics that are, in general, less effective, depending on which infection you’re talking about,” Dr. Ramsey said. “The [second-line antibiotics] have more side effects. And there’s data to show that patients with [a] penicillin allergy label have longer hospital stays, more costly hospital stays, are at risk for more resistant infections. And it breeds antimicrobial resistance in the long-term.”

Dr. Ramsey had no relevant financial disclosures.

SOURCE: Ramsey AC et al. AAAAI/WAO Joint Congress, Abstract 104.

KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.

She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

M. Alexander Otto/Frontline Medical News

Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.

She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.

“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.

As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.

Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

aotto@frontlinemedcom.com

KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.

She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

M. Alexander Otto/Frontline Medical News

Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.

She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.

“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.

As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.

Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

aotto@frontlinemedcom.com

KAUAI, HAWAII – Gentler vacuum pressure seems to reduce the risk of paradoxical adipose hyperplasia after cryolipolysis, according to Suzanne Kilmer, MD, director of the Laser and Skin Surgery Center of Northern California, Sacramento.

She and her colleagues have noticed a reduction with the newer CoolAdvantage applicators from Zeltiq Aesthetics, the manufacturer of CoolSculpting equipment. CoolAdvantage runs colder and with less suction than earlier applicators. “It seems to work equally as well,” but with shorter treatment times, less bruising, and less discomfort. Although paradoxical adipose hyperplasia (PAH) “is incredibly rare, it is something we want to reduce, and we do see decreased incidence with these new applicators,” Dr. Kilmer said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

M. Alexander Otto/Frontline Medical News

Another newer option from the manufacturer is the CoolMini applicator for submental fat. Dr. Kilmer generally does two overlapping applications with the CoolMini in the same session, in order to cover as much chin fat as possible. There will be what looks like a stick of butter under the chin when the applicators are removed; it goes away after a few minutes of massage. Patient satisfaction is high, but there can be unveiling of the platysmal bands, which is “something you want to talk to patients about ahead of time,” she said.

She sometimes uses the CoolMini first, followed by the other recently available option for submental fat, deoxycholic acid (Kybella). “We shrink down everything we can with CoolSculpting, and then come back with Kybella to clean up whatever’s left.” Using this approach, patients are injected with less deoxycholic acid, with less inflammation, she said.

“I think you get more fat loss out of a given CoolSculpting treatment than you do with Kybella,” said Dr. Kilmer, who noted that deoxycholic acid is also an option for PAH.

As for going off label with CoolSculpting for jowls, “we’ve done it, and I tell everybody there’s a chance of a 2-3 month palsy. All you are really doing is demyelinating the nerve, not injuring it. If you do liposuction, you actually have a little bit of risk of actually injuring it. You can use a nerve stimulator to map out the nerves beforehand,” she said.

Dr. Kilmer is a consultant for Zeltiq Aesthetics, and an investigator on many of the company’s development trials. She’s also a consultant for Allergan, manufacturer of Kybella, which recently acquired Zeltiq. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

aotto@frontlinemedcom.com

SAN DIEGO – Pediatric hematologists should consider testing for vitamin D deficiency to optimize bone health in children who will be receiving chronic anticoagulation. That’s a key message from a single-center retrospective review presented during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“More research is needed to determine which children should be targeted for screening for low [bone mineral density], though our research suggests that children with prolonged treatment with steroids may be at the highest risk,” Kavita N. Patel, MD, one of the study’s authors, said in an interview.

The study population was a retrospective cohort of children aged 10-21 years who received anticoagulation for more than 1 year at Children’s Healthcare of Atlanta between Jan. 2, 2012, and Oct. 15, 2017. The researchers evaluated a number of factors, including demographic variables, anticoagulants used, vitamin D status, previously reported comorbid conditions and medications associated with changes in BMD. They defined vitamin D deficiency as less than 20 ng/mL and insufficiency as 20-29 ng/mL.

Dr. Patel reported results from 27 males and 23 females. Of these, 15 (30%) underwent bone density testing with dual-energy X-ray absorptiometry; 5 (10%) did not undergo dual-energy X-ray absorptiometry testing because there is no age-specific standardization below the age of 5 years. Nearly half of the patients (42%) were Caucasian, 34% were African American, 16% were Hispanic, and the rest were from other ethnicities. The top four common indications for extended anticoagulation were recurrent venous thromboembolism (26%), extended treatment for deep vein thrombosis (18%), antiphospholipid syndrome (14%), and thrombophilia plus a single venous thromboembolism (14%).

The anticoagulants most often utilized were enoxaparin (59%), warfarin (29%), and rivaroxaban (7%). The most frequent risk factor for low BMD was long-term use of steroids (16%; defined as greater than 6 months of continuous use in the year prior to BMD testing).

Vitamin D deficiency was identified in 52% of subjects who were tested, while another 24% had insufficient levels of vitamin D. Overall, the median lumbar spine z score was –1.4. Five (30%) subjects who completed BMD testing had low BMD, with median z score of –2.5. None met fracture criteria for pediatric osteoporosis. On linear regression, the only factor found to be significantly associated with a BMD lumbar spine z score in chronically anticoagulated children was the long-term use of steroids (P = .04).

Dr. Patel acknowledged certain limitations of the study, including its single-center design and the fact that not all of the children receiving chronic anticoagulation could be tested.

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Patel KN et al. THSNA 2018, Poster 65.

SAN DIEGO – Pediatric hematologists should consider testing for vitamin D deficiency to optimize bone health in children who will be receiving chronic anticoagulation. That’s a key message from a single-center retrospective review presented during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“More research is needed to determine which children should be targeted for screening for low [bone mineral density], though our research suggests that children with prolonged treatment with steroids may be at the highest risk,” Kavita N. Patel, MD, one of the study’s authors, said in an interview.

The study population was a retrospective cohort of children aged 10-21 years who received anticoagulation for more than 1 year at Children’s Healthcare of Atlanta between Jan. 2, 2012, and Oct. 15, 2017. The researchers evaluated a number of factors, including demographic variables, anticoagulants used, vitamin D status, previously reported comorbid conditions and medications associated with changes in BMD. They defined vitamin D deficiency as less than 20 ng/mL and insufficiency as 20-29 ng/mL.

Dr. Patel reported results from 27 males and 23 females. Of these, 15 (30%) underwent bone density testing with dual-energy X-ray absorptiometry; 5 (10%) did not undergo dual-energy X-ray absorptiometry testing because there is no age-specific standardization below the age of 5 years. Nearly half of the patients (42%) were Caucasian, 34% were African American, 16% were Hispanic, and the rest were from other ethnicities. The top four common indications for extended anticoagulation were recurrent venous thromboembolism (26%), extended treatment for deep vein thrombosis (18%), antiphospholipid syndrome (14%), and thrombophilia plus a single venous thromboembolism (14%).

The anticoagulants most often utilized were enoxaparin (59%), warfarin (29%), and rivaroxaban (7%). The most frequent risk factor for low BMD was long-term use of steroids (16%; defined as greater than 6 months of continuous use in the year prior to BMD testing).

Vitamin D deficiency was identified in 52% of subjects who were tested, while another 24% had insufficient levels of vitamin D. Overall, the median lumbar spine z score was –1.4. Five (30%) subjects who completed BMD testing had low BMD, with median z score of –2.5. None met fracture criteria for pediatric osteoporosis. On linear regression, the only factor found to be significantly associated with a BMD lumbar spine z score in chronically anticoagulated children was the long-term use of steroids (P = .04).

Dr. Patel acknowledged certain limitations of the study, including its single-center design and the fact that not all of the children receiving chronic anticoagulation could be tested.

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Patel KN et al. THSNA 2018, Poster 65.

SAN DIEGO – Pediatric hematologists should consider testing for vitamin D deficiency to optimize bone health in children who will be receiving chronic anticoagulation. That’s a key message from a single-center retrospective review presented during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“More research is needed to determine which children should be targeted for screening for low [bone mineral density], though our research suggests that children with prolonged treatment with steroids may be at the highest risk,” Kavita N. Patel, MD, one of the study’s authors, said in an interview.

The study population was a retrospective cohort of children aged 10-21 years who received anticoagulation for more than 1 year at Children’s Healthcare of Atlanta between Jan. 2, 2012, and Oct. 15, 2017. The researchers evaluated a number of factors, including demographic variables, anticoagulants used, vitamin D status, previously reported comorbid conditions and medications associated with changes in BMD. They defined vitamin D deficiency as less than 20 ng/mL and insufficiency as 20-29 ng/mL.

Dr. Patel reported results from 27 males and 23 females. Of these, 15 (30%) underwent bone density testing with dual-energy X-ray absorptiometry; 5 (10%) did not undergo dual-energy X-ray absorptiometry testing because there is no age-specific standardization below the age of 5 years. Nearly half of the patients (42%) were Caucasian, 34% were African American, 16% were Hispanic, and the rest were from other ethnicities. The top four common indications for extended anticoagulation were recurrent venous thromboembolism (26%), extended treatment for deep vein thrombosis (18%), antiphospholipid syndrome (14%), and thrombophilia plus a single venous thromboembolism (14%).

The anticoagulants most often utilized were enoxaparin (59%), warfarin (29%), and rivaroxaban (7%). The most frequent risk factor for low BMD was long-term use of steroids (16%; defined as greater than 6 months of continuous use in the year prior to BMD testing).

Vitamin D deficiency was identified in 52% of subjects who were tested, while another 24% had insufficient levels of vitamin D. Overall, the median lumbar spine z score was –1.4. Five (30%) subjects who completed BMD testing had low BMD, with median z score of –2.5. None met fracture criteria for pediatric osteoporosis. On linear regression, the only factor found to be significantly associated with a BMD lumbar spine z score in chronically anticoagulated children was the long-term use of steroids (P = .04).

Dr. Patel acknowledged certain limitations of the study, including its single-center design and the fact that not all of the children receiving chronic anticoagulation could be tested.

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Patel KN et al. THSNA 2018, Poster 65.

Stratification of colorectal cancer (CRC) risk was enhanced by joint consideration of the independent family history and genetic risk score predictors, according to an ongoing population-based, case-control study of patients recruited during 2003-2010.

Courtesy Wikimedia Commons/Nephron/Creative Commons License

The research was conducted using data from DACHS (Colorectal Cancer: Chances for Prevention Through Screening), an ongoing population-based, case-control study in Germany, reported Korbinian Weigl, PhD, and his colleagues in the journal Clinical Epidemiology (doi: 10.2147/CLEP.S145636). They included 2,363 eligible CRC patients who were identified by 22 participating hospitals and frequency matched with respect to sex, age, and residential location to 2,198 randomly selected controls that had genome-wide association studies data. The population consisted of 40% women, and the median ages for cases and controls were 69 and 70 years, respectively.

Genetic risk score was calculated by genotyping 53 single-nucleotide polymorphisms reported in published literature to be associated with higher CRC risk for individuals of European descent. Seven genetic risk score groups – very low, low, low-medium, medium, medium-high, high, and very high – were established according to categories generated on the basis of weighted risk allele distribution among controls. Family history referred to CRC in first-degree and second-degree relatives. Selected potential confounders included age, sex, body mass index, education, hormone replacement therapy in women, smoking, and colonoscopy history. Odds ratios with 95% confidence intervals were estimated by multiple logistic regression models that included adjustment for potential confounders. Statistical calculations examined individual and joint family history and genetic risk score associations with risk for CRC and the effect of potential confounding factors.

At least one colonoscopy was performed on over half the individuals in the control group, while a significantly lower number (P less than .0001) were performed on case individuals (22.1%). Family history of CRC in first-degree relatives was reported by 316 case participants (13.4%) and 214 controls (9.7%; P less than .0001). The calculated genetic risk score ranged from 20 to 48, with a substantially higher proportion of cases in the higher deciles.

Investigators compared the risk for CRC in the top decile with that in the lowest and found an increased risk of 2.9-fold (OR, 2.94) based on genetic risk analysis adjusted for sex and age and an increased risk of 3.0-fold (OR, 3.0) when all other covariates except family history were included. Comparing results against analysis with the 27 single-nucleotide polymorphisms that had been used in previous studies indicated a sizable improvement in genetic risk stratification as a result of increasing the number of single-nucleotide polymorphisms (P value for increase in c statistic = .003) included in the analysis.

Risk associated with having a family history of CRC in a first-degree relative was 1.5-fold (OR, 1.47) higher in an age- and sex-adjusted analysis. Risk prediction increased to an OR of 1.86 when calculations were adjusted with covariates, especially with previous colonoscopies. Using genetic risk scoring as a calculation adjustment only slightly changed the result (OR, 1.83). A similar trend, but with lower-magnitude associations, was observed with family history of CRC in second-degree relatives.

A dose-response association between the number of risk alleles and CRC risk determined by a logistic regression model revealed a curvilinear relationship between genetic risk score and CRC risk. At higher genetic risk score levels, the increase in CRC risk was particularly strong. The dose-response association indicated an independent relationship between family history and CRC such that individuals with first-degree relatives with CRC will reach the same risk level with a lower genetic risk score as those with a higher genetic risk score but no first-degree relatives with CRC.

SOURCE: Weigl K et al. Clin Epidemiol. 2018;10:143-52.
 

Stratification of colorectal cancer (CRC) risk was enhanced by joint consideration of the independent family history and genetic risk score predictors, according to an ongoing population-based, case-control study of patients recruited during 2003-2010.

Courtesy Wikimedia Commons/Nephron/Creative Commons License

The research was conducted using data from DACHS (Colorectal Cancer: Chances for Prevention Through Screening), an ongoing population-based, case-control study in Germany, reported Korbinian Weigl, PhD, and his colleagues in the journal Clinical Epidemiology (doi: 10.2147/CLEP.S145636). They included 2,363 eligible CRC patients who were identified by 22 participating hospitals and frequency matched with respect to sex, age, and residential location to 2,198 randomly selected controls that had genome-wide association studies data. The population consisted of 40% women, and the median ages for cases and controls were 69 and 70 years, respectively.

Genetic risk score was calculated by genotyping 53 single-nucleotide polymorphisms reported in published literature to be associated with higher CRC risk for individuals of European descent. Seven genetic risk score groups – very low, low, low-medium, medium, medium-high, high, and very high – were established according to categories generated on the basis of weighted risk allele distribution among controls. Family history referred to CRC in first-degree and second-degree relatives. Selected potential confounders included age, sex, body mass index, education, hormone replacement therapy in women, smoking, and colonoscopy history. Odds ratios with 95% confidence intervals were estimated by multiple logistic regression models that included adjustment for potential confounders. Statistical calculations examined individual and joint family history and genetic risk score associations with risk for CRC and the effect of potential confounding factors.

At least one colonoscopy was performed on over half the individuals in the control group, while a significantly lower number (P less than .0001) were performed on case individuals (22.1%). Family history of CRC in first-degree relatives was reported by 316 case participants (13.4%) and 214 controls (9.7%; P less than .0001). The calculated genetic risk score ranged from 20 to 48, with a substantially higher proportion of cases in the higher deciles.

Investigators compared the risk for CRC in the top decile with that in the lowest and found an increased risk of 2.9-fold (OR, 2.94) based on genetic risk analysis adjusted for sex and age and an increased risk of 3.0-fold (OR, 3.0) when all other covariates except family history were included. Comparing results against analysis with the 27 single-nucleotide polymorphisms that had been used in previous studies indicated a sizable improvement in genetic risk stratification as a result of increasing the number of single-nucleotide polymorphisms (P value for increase in c statistic = .003) included in the analysis.

Risk associated with having a family history of CRC in a first-degree relative was 1.5-fold (OR, 1.47) higher in an age- and sex-adjusted analysis. Risk prediction increased to an OR of 1.86 when calculations were adjusted with covariates, especially with previous colonoscopies. Using genetic risk scoring as a calculation adjustment only slightly changed the result (OR, 1.83). A similar trend, but with lower-magnitude associations, was observed with family history of CRC in second-degree relatives.

A dose-response association between the number of risk alleles and CRC risk determined by a logistic regression model revealed a curvilinear relationship between genetic risk score and CRC risk. At higher genetic risk score levels, the increase in CRC risk was particularly strong. The dose-response association indicated an independent relationship between family history and CRC such that individuals with first-degree relatives with CRC will reach the same risk level with a lower genetic risk score as those with a higher genetic risk score but no first-degree relatives with CRC.

SOURCE: Weigl K et al. Clin Epidemiol. 2018;10:143-52.
 

Stratification of colorectal cancer (CRC) risk was enhanced by joint consideration of the independent family history and genetic risk score predictors, according to an ongoing population-based, case-control study of patients recruited during 2003-2010.

Courtesy Wikimedia Commons/Nephron/Creative Commons License

The research was conducted using data from DACHS (Colorectal Cancer: Chances for Prevention Through Screening), an ongoing population-based, case-control study in Germany, reported Korbinian Weigl, PhD, and his colleagues in the journal Clinical Epidemiology (doi: 10.2147/CLEP.S145636). They included 2,363 eligible CRC patients who were identified by 22 participating hospitals and frequency matched with respect to sex, age, and residential location to 2,198 randomly selected controls that had genome-wide association studies data. The population consisted of 40% women, and the median ages for cases and controls were 69 and 70 years, respectively.

Genetic risk score was calculated by genotyping 53 single-nucleotide polymorphisms reported in published literature to be associated with higher CRC risk for individuals of European descent. Seven genetic risk score groups – very low, low, low-medium, medium, medium-high, high, and very high – were established according to categories generated on the basis of weighted risk allele distribution among controls. Family history referred to CRC in first-degree and second-degree relatives. Selected potential confounders included age, sex, body mass index, education, hormone replacement therapy in women, smoking, and colonoscopy history. Odds ratios with 95% confidence intervals were estimated by multiple logistic regression models that included adjustment for potential confounders. Statistical calculations examined individual and joint family history and genetic risk score associations with risk for CRC and the effect of potential confounding factors.

At least one colonoscopy was performed on over half the individuals in the control group, while a significantly lower number (P less than .0001) were performed on case individuals (22.1%). Family history of CRC in first-degree relatives was reported by 316 case participants (13.4%) and 214 controls (9.7%; P less than .0001). The calculated genetic risk score ranged from 20 to 48, with a substantially higher proportion of cases in the higher deciles.

Investigators compared the risk for CRC in the top decile with that in the lowest and found an increased risk of 2.9-fold (OR, 2.94) based on genetic risk analysis adjusted for sex and age and an increased risk of 3.0-fold (OR, 3.0) when all other covariates except family history were included. Comparing results against analysis with the 27 single-nucleotide polymorphisms that had been used in previous studies indicated a sizable improvement in genetic risk stratification as a result of increasing the number of single-nucleotide polymorphisms (P value for increase in c statistic = .003) included in the analysis.

Risk associated with having a family history of CRC in a first-degree relative was 1.5-fold (OR, 1.47) higher in an age- and sex-adjusted analysis. Risk prediction increased to an OR of 1.86 when calculations were adjusted with covariates, especially with previous colonoscopies. Using genetic risk scoring as a calculation adjustment only slightly changed the result (OR, 1.83). A similar trend, but with lower-magnitude associations, was observed with family history of CRC in second-degree relatives.

A dose-response association between the number of risk alleles and CRC risk determined by a logistic regression model revealed a curvilinear relationship between genetic risk score and CRC risk. At higher genetic risk score levels, the increase in CRC risk was particularly strong. The dose-response association indicated an independent relationship between family history and CRC such that individuals with first-degree relatives with CRC will reach the same risk level with a lower genetic risk score as those with a higher genetic risk score but no first-degree relatives with CRC.

SOURCE: Weigl K et al. Clin Epidemiol. 2018;10:143-52.
 

Elderly individuals who have excessive daytime sleepiness might be more susceptible to accumulation of an Alzheimer’s disease (AD) biomarker, results of a prospective, longitudinal cohort study suggest.

In the study, excessive daytime sleepiness (EDS) was associated with increased accumulation of beta-amyloid, an important biomarker of AD that manifests in early preclinical stages, wrote first author Diego Z. Carvalho, MD, and his colleagues at the Mayo Clinic, Rochester, Minn. The report was published online March 12 in JAMA Neurology.

Jupiterimages/Thinkstock

The prospective, longitudinal cohort analysis from Dr. Carvalho and his colleagues included 283 participants age 70 or older without a diagnosis of dementia who filled out a sleepiness assessment survey and underwent baseline and follow-up imaging studies as part of the Mayo Clinic Study of Aging.

All participants included in the analysis underwent at least two consecutive carbon 11–labeled Pittsburgh compound B PET (PiB-PET) scans. EDS, defined as a score of at least 10 on the Epworth Sleepiness Scale, was seen in 63 participants (22.3%), the researchers found.

At baseline, EDS was significantly associated with increased beta-amyloid accumulation in the anterior cingulate (P = .04), posterior cingulate-precuneus (P = .02), and parietal (P = .04) regions. The association between EDS and longitudinal beta-amyloid accumulation was most pronounced in participants who had global PiB positivity at baseline in anterior cingulate and cingulate-precuneus regions (P = .02 for both), they reported.

Findings of the study are consistent with a previous investigation of middle-aged participants without dementia, Dr. Carvalho and coauthors said in a discussion of the results. In that study, increased daytime somnolence was associated with increased beta-amyloid burden in regions including the precuneus and anterior cingulate. Daytime sleepiness in that study was measured using a different measure, the Sleep Scale, which was originally developed as part of the Medical Outcomes Study.

Further investigation of the link between EDS and beta-amyloid accumulation is needed. In particular, the researchers suggested that future studies might evaluate whether amyloid accumulation can be avoided through early recognition of EDS and subsequent treatment of the underlying sleep disorder.

The study was funded by grants from the National Institutes of Health and several foundations. Dr. Carvalho reported no disclosures related to the study. Many of his coauthors reported relationships with a variety of pharmaceutical companies developing therapies for Alzheimer’s.

SOURCE: Carvalho D et al., JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0049

Elderly individuals who have excessive daytime sleepiness might be more susceptible to accumulation of an Alzheimer’s disease (AD) biomarker, results of a prospective, longitudinal cohort study suggest.

In the study, excessive daytime sleepiness (EDS) was associated with increased accumulation of beta-amyloid, an important biomarker of AD that manifests in early preclinical stages, wrote first author Diego Z. Carvalho, MD, and his colleagues at the Mayo Clinic, Rochester, Minn. The report was published online March 12 in JAMA Neurology.

Jupiterimages/Thinkstock

The prospective, longitudinal cohort analysis from Dr. Carvalho and his colleagues included 283 participants age 70 or older without a diagnosis of dementia who filled out a sleepiness assessment survey and underwent baseline and follow-up imaging studies as part of the Mayo Clinic Study of Aging.

All participants included in the analysis underwent at least two consecutive carbon 11–labeled Pittsburgh compound B PET (PiB-PET) scans. EDS, defined as a score of at least 10 on the Epworth Sleepiness Scale, was seen in 63 participants (22.3%), the researchers found.

At baseline, EDS was significantly associated with increased beta-amyloid accumulation in the anterior cingulate (P = .04), posterior cingulate-precuneus (P = .02), and parietal (P = .04) regions. The association between EDS and longitudinal beta-amyloid accumulation was most pronounced in participants who had global PiB positivity at baseline in anterior cingulate and cingulate-precuneus regions (P = .02 for both), they reported.

Findings of the study are consistent with a previous investigation of middle-aged participants without dementia, Dr. Carvalho and coauthors said in a discussion of the results. In that study, increased daytime somnolence was associated with increased beta-amyloid burden in regions including the precuneus and anterior cingulate. Daytime sleepiness in that study was measured using a different measure, the Sleep Scale, which was originally developed as part of the Medical Outcomes Study.

Further investigation of the link between EDS and beta-amyloid accumulation is needed. In particular, the researchers suggested that future studies might evaluate whether amyloid accumulation can be avoided through early recognition of EDS and subsequent treatment of the underlying sleep disorder.

The study was funded by grants from the National Institutes of Health and several foundations. Dr. Carvalho reported no disclosures related to the study. Many of his coauthors reported relationships with a variety of pharmaceutical companies developing therapies for Alzheimer’s.

SOURCE: Carvalho D et al., JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0049

Elderly individuals who have excessive daytime sleepiness might be more susceptible to accumulation of an Alzheimer’s disease (AD) biomarker, results of a prospective, longitudinal cohort study suggest.

In the study, excessive daytime sleepiness (EDS) was associated with increased accumulation of beta-amyloid, an important biomarker of AD that manifests in early preclinical stages, wrote first author Diego Z. Carvalho, MD, and his colleagues at the Mayo Clinic, Rochester, Minn. The report was published online March 12 in JAMA Neurology.

Jupiterimages/Thinkstock

The prospective, longitudinal cohort analysis from Dr. Carvalho and his colleagues included 283 participants age 70 or older without a diagnosis of dementia who filled out a sleepiness assessment survey and underwent baseline and follow-up imaging studies as part of the Mayo Clinic Study of Aging.

All participants included in the analysis underwent at least two consecutive carbon 11–labeled Pittsburgh compound B PET (PiB-PET) scans. EDS, defined as a score of at least 10 on the Epworth Sleepiness Scale, was seen in 63 participants (22.3%), the researchers found.

At baseline, EDS was significantly associated with increased beta-amyloid accumulation in the anterior cingulate (P = .04), posterior cingulate-precuneus (P = .02), and parietal (P = .04) regions. The association between EDS and longitudinal beta-amyloid accumulation was most pronounced in participants who had global PiB positivity at baseline in anterior cingulate and cingulate-precuneus regions (P = .02 for both), they reported.

Findings of the study are consistent with a previous investigation of middle-aged participants without dementia, Dr. Carvalho and coauthors said in a discussion of the results. In that study, increased daytime somnolence was associated with increased beta-amyloid burden in regions including the precuneus and anterior cingulate. Daytime sleepiness in that study was measured using a different measure, the Sleep Scale, which was originally developed as part of the Medical Outcomes Study.

Further investigation of the link between EDS and beta-amyloid accumulation is needed. In particular, the researchers suggested that future studies might evaluate whether amyloid accumulation can be avoided through early recognition of EDS and subsequent treatment of the underlying sleep disorder.

The study was funded by grants from the National Institutes of Health and several foundations. Dr. Carvalho reported no disclosures related to the study. Many of his coauthors reported relationships with a variety of pharmaceutical companies developing therapies for Alzheimer’s.

SOURCE: Carvalho D et al., JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0049