Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

Click here to access August 2019 Advances in Hematology and Oncology

Table of Contents

• Partners in Oncology Care: Coordinated Follicular Lymphoma Management
• Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer
• Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival
• Review of Radiologic Considerations in an Immunocompetent Patient With Primary Central Nervous System Lymphoma
• Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms
• Timely Diagnosis of Lung Cancer in a Dedicated VA Referral Unit With Endobronchial Ultrasound
• Research News: Darolutamide Approved for Nonmetastatic CRPC
• Roundtable: Genomic Medicine and Genetic Counseling in the VA and DoD

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The impact of prediagnosis aspirin use on mortality in women with breast cancer is significantly tied to epigenetic changes in certain breast cancer-related genes, investigators reported.

While studies have shown aspirin reduces the risk of breast cancer development, there is limited and inconsistent data on the effect of aspirin on prognosis and mortality after a diagnosis of breast cancer, Tengteng Wang, PhD, from the department of epidemiology at the University of North Carolina at Chapel Hill and coauthors wrote in Cancer.

To address this, they analyzed data from 1,508 women who had a first diagnosis of primary breast cancer and were involved in the Long Island Breast Cancer Study Project; they then looked at the women’s methylation status, which is a mechanism of epigenetic change.

Around one in five participants reported ever using aspirin, and the analysis showed that ever use of aspirin was associated with an overall 13% decrease in breast cancer–specific mortality.

However researchers saw significant interactions between aspirin use and LINE-1 methylation status – which is a marker of methylation of genetic elements that play key roles in maintaining genomic stability – and breast cancer–specific genes.

They found that aspirin use in women with LINE-1 hypomethylation was associated with a risk of breast cancer–specific mortality that was 45% higher than that of nonusers (P = .05).

Compared with nonusers, aspirin users with methylated tumor BRCA1 promoter had significant 16% higher breast cancer mortality (P = .04) and 67% higher all-cause mortality (P = .02). However the study showed aspirin did not affect mortality in women with unmethylated BRCA1 promoter.

Among women with the PR breast cancer gene, aspirin use by those with methylation of the PR promoter was associated with a 63% higher breast cancer–specific mortality, but methylation showed no statistically significant effect on all-cause mortality, compared with nonusers.

The study found no significant change when they restricted the analysis to receptor-positive or invasive breast cancer, and the associations remained consistent even after adjusting for global methylation.

“Our findings suggest that the association between aspirin use and mortality after breast cancer may depend on methylation profiles and warrant further investigation,” the authors wrote. “These findings, if confirmed, may provide new biological insights into the association between aspirin use and breast cancer prognosis, may affect clinical decision making by identifying a subgroup of patients with breast cancer using epigenetic markers for whom prediagnosis aspirin use affects subsequent mortality, and may help refine risk-reduction strategies to improve survival among women with breast cancer.”

The study was partly supported by the National Institutes of Health. One author declared personal fees from the private sector outside the submitted work.

SOURCE: Wang T et al. Cancer. 2019 Aug 12. doi: 10.1002/cncr.32364.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

The vascular specialty has had many coding changes over the past five to six years. It is sometimes difficult to keep up with the changes from year to year, but attending the SVS Coding & Reimbursement workshop, to be held on Sept. 20-21 in Rosemont, Ill., is sure to help. Coding is critical in every practice model – whether it be private, academic or employed. If it is not done accurately, money will be lost. This intensive course will give attendees the knowledge they need to make a positive impact on their coding procedures. All those who wish to improve and expand their knowledge of accurate coding and reimbursement for vascular surgery should attend. Learn more and register here.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

Psoriasis is associated with systemic inflammation, which heightens the risk of blood vessel disease and diabetes. Therefore, the finding, while notable, may not have been entirely unexpected. Biologic therapy (BT) for psoriasis was already found to be favorably associated with luminal coronary plaque, the researchers say, but it was not clear whether those associations were attributable to direct anti-inflammatory effects on the coronary arteries. They wanted to find out whether the perivascular fat attenuation index (FAI) would offer clues. FAI is a new method of analyzing CT scans by assessing whether the fat tissue surrounding arteries becomes attenuated, or less fatty.

The researchers investigated their premise in 134 participants from an ongoing NIH study, the Psoriasis Atherosclerosis Cardiometabolic Initiative cohort. Of the participants, 82 had been receiving anti-tumor necrosis factor α, anti-interleukin (IL) 12/23, or anti-IL-17 for 1 year. The remaining 52 had not received any BT, and given topical or light therapy. The patients underwent CT scans at the start of the study and 1 year later. All of the patients had low cardiovascular risk. At baseline, 27 in the treated group and 19 in the untreated group had a focal coronary atherosclerotic plaque.

The study found that an abnormal perivascular FAI was linked to a 6- to 9-fold increased risk of major adverse cardiovascular events, study coauthor Charalambos Antoniades, MD, says. Patients on BT had a significant decrease in FAI at 1 year, as well as improved psoriasis symptoms. Even patients with preexisting coronary artery plaque had a reduction in coronary inflammation after BT. No change was seen in the untreated patients. The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

The researchers say their findings have implications for other chronic inflammatory diseases, such as lupus and rheumatoid arthritis, which are known to raise the risk for heart attacks and stroke.

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

mzoler@mdedge.com

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

mzoler@mdedge.com

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12

PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.

In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.

Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.

The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.

In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.

Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.

Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.

The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.

PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.

mzoler@mdedge.com

SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12

People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

msullivan@mdedge.com

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

msullivan@mdedge.com

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

msullivan@mdedge.com

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

bjancin@mdedge.com

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

bjancin@mdedge.com

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

bjancin@mdedge.com