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Early intensive treatment of MS may benefit patients
First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.
In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”
The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).
At baseline, patients who received early intensive treatment had higher average EDSS scores, compared with patients treated with an escalation approach (4.2 vs. 3.5). After 5 years, the average increase in EDSS score was lower among patients who received early intensive treatment, compared with patients treated with an escalation approach (0.3 vs. 1.2). The researchers adjusted for patients’ sex, age at treatment, year of starting treatment, and escalation to high-efficacy treatment in the escalation treatment approach group.
Median time to sustained accumulation of disability was 6.0 years for the early intensive therapy group and 3.1 years for the escalation therapy group, but the risk of sustained accumulation of disability did not differ between the groups after adjustment for covariates.
“Although patients were selected to receive early intensive treatment on the basis of poor prognostic factors, including more active disease, it was this patient group that had better long-term outcomes,” Dr. Harding and her colleagues wrote.
There were no treatment-related deaths in the study. Among patients who received alemtuzumab, 87% developed infusion-related adverse events, and 47% developed autoimmunity. Among patients receiving natalizumab, there were no serious adverse events and no cases of progressive multifocal leukoencephalopathy. In patients receiving moderate-efficacy disease-modifying therapies, there were seven serious adverse events (1.4%).
Dr. Harding disclosed grants from Novartis UK outside the present study. Coauthors reported honoraria, support to attend educational meetings, and travel expenses, as well as grants and salary outside the present study, from various pharmaceutical companies, including Biogen, Teva, Roche, MedDay Pharma, Merck, Genzyme, and Novartis.
SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905
First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.
In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”
The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).
At baseline, patients who received early intensive treatment had higher average EDSS scores, compared with patients treated with an escalation approach (4.2 vs. 3.5). After 5 years, the average increase in EDSS score was lower among patients who received early intensive treatment, compared with patients treated with an escalation approach (0.3 vs. 1.2). The researchers adjusted for patients’ sex, age at treatment, year of starting treatment, and escalation to high-efficacy treatment in the escalation treatment approach group.
Median time to sustained accumulation of disability was 6.0 years for the early intensive therapy group and 3.1 years for the escalation therapy group, but the risk of sustained accumulation of disability did not differ between the groups after adjustment for covariates.
“Although patients were selected to receive early intensive treatment on the basis of poor prognostic factors, including more active disease, it was this patient group that had better long-term outcomes,” Dr. Harding and her colleagues wrote.
There were no treatment-related deaths in the study. Among patients who received alemtuzumab, 87% developed infusion-related adverse events, and 47% developed autoimmunity. Among patients receiving natalizumab, there were no serious adverse events and no cases of progressive multifocal leukoencephalopathy. In patients receiving moderate-efficacy disease-modifying therapies, there were seven serious adverse events (1.4%).
Dr. Harding disclosed grants from Novartis UK outside the present study. Coauthors reported honoraria, support to attend educational meetings, and travel expenses, as well as grants and salary outside the present study, from various pharmaceutical companies, including Biogen, Teva, Roche, MedDay Pharma, Merck, Genzyme, and Novartis.
SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905
First-line treatment of multiple sclerosis with a high-efficacy therapy may produce better long-term outcomes than does an escalation treatment approach, data from a real-world cohort study suggest.
In a population-based cohort of patients with multiple sclerosis (MS) in southeast Wales, those who initiated treatment with a high-efficacy therapy had a smaller average increase in Expanded Disability Status Scale (EDSS) score after 5 years, compared with patients who started on moderate-efficacy therapy, researchers reported Feb. 18 in JAMA Neurology. These outcomes occurred “despite clinical surveillance and targeted escalation” in the group of patients who started on moderate-efficacy drugs, said first author Katharine Harding, PhD, of Cardiff University and the University Hospital of Wales in Cardiff and the Royal Gwent Hospital, Newport, Wales, and her colleagues. “These findings suggest that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes and support the need for a prospective clinical trial to compare disease-modifying therapy algorithms.”
The investigators analyzed data collected between January 1998 and December 2016 from 592 patients with MS. Of the 592 patients, 104 initiated treatment with alemtuzumab (Lemtrada) or natalizumab (Tysabri), which the researchers classified as high-efficacy therapies (i.e., early intensive treatment), and 488 initiated treatment with interferons, glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or teriflunomide (Aubagio), which were considered moderate-efficacy therapies (i.e., escalation approach).
At baseline, patients who received early intensive treatment had higher average EDSS scores, compared with patients treated with an escalation approach (4.2 vs. 3.5). After 5 years, the average increase in EDSS score was lower among patients who received early intensive treatment, compared with patients treated with an escalation approach (0.3 vs. 1.2). The researchers adjusted for patients’ sex, age at treatment, year of starting treatment, and escalation to high-efficacy treatment in the escalation treatment approach group.
Median time to sustained accumulation of disability was 6.0 years for the early intensive therapy group and 3.1 years for the escalation therapy group, but the risk of sustained accumulation of disability did not differ between the groups after adjustment for covariates.
“Although patients were selected to receive early intensive treatment on the basis of poor prognostic factors, including more active disease, it was this patient group that had better long-term outcomes,” Dr. Harding and her colleagues wrote.
There were no treatment-related deaths in the study. Among patients who received alemtuzumab, 87% developed infusion-related adverse events, and 47% developed autoimmunity. Among patients receiving natalizumab, there were no serious adverse events and no cases of progressive multifocal leukoencephalopathy. In patients receiving moderate-efficacy disease-modifying therapies, there were seven serious adverse events (1.4%).
Dr. Harding disclosed grants from Novartis UK outside the present study. Coauthors reported honoraria, support to attend educational meetings, and travel expenses, as well as grants and salary outside the present study, from various pharmaceutical companies, including Biogen, Teva, Roche, MedDay Pharma, Merck, Genzyme, and Novartis.
SOURCE: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905
FROM JAMA NEUROLOGY
Key clinical point:
Major finding: After 5 years, the average increase in Expanded Disability Status Scale score was lower among patients who received early intensive treatment, compared with patients treated with an escalation approach (0.3 vs. 1.2).
Study details: A population-based cohort study of 592 patients with MS in southeast Wales.
Disclosures: Dr. Harding disclosed grants from Novartis UK outside the present study. Coauthors reported honoraria, support to attend educational meetings, and travel expenses, as well as grants and salary outside the present study, from various pharmaceutical companies, including Biogen, Teva, Roche, MedDay Pharma, Merck, Genzyme, and Novartis.
Source: Harding K et al. JAMA Neurol. 2019 Feb 18. doi: 10.1001/jamaneurol.2018.4905.
Hormone therapy in transgender individuals may up risk of CV events
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
FROM CIRCULATION
Mediterranean diet cut Parkinson’s risk
‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
‘Telereferrals’ improved mental health referral follow-through for children. How to take action to cut cardiovascular disease risk in rheumatoid patients. And the U.S. Preventive Services Task Force recommends counseling for perinatal depression prevention.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Culture change needed to improve gender inequalities in medicine
LONDON –
“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.
“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”
For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.
Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.
“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”
Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.
“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”
Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.
That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).
“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.
Women’s credentials and capabilities were often felt to be less respected by male colleagues, and there was talk of being met with microaggressions in the workplace, as in one example given by Nana Odom, MSc, a clinical engineer at the Royal United Hospital Bath (England). She was told “you’re not an engineer, because I have not got a set of screwdrivers and sit at a computer and program.” Such comments can deeply affect a person, Dr. Odom said. “Sometimes I feel that if I don’t go into the workshop and open up a bit of kit that I am not an engineer, but it’s so unconscious, it carries on with you.” These types of stories need to be told so then they can be properly addressed when they do happen, she said.
Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.
“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.
“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”
Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.
All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.
“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.
Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”
No financial disclosures were reported by any of the speakers quoted.
SOURCE: Lancet. 2019;393:493–610, e6-e28
LONDON –
“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.
“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”
For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.
Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.
“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”
Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.
“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”
Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.
That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).
“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.
Women’s credentials and capabilities were often felt to be less respected by male colleagues, and there was talk of being met with microaggressions in the workplace, as in one example given by Nana Odom, MSc, a clinical engineer at the Royal United Hospital Bath (England). She was told “you’re not an engineer, because I have not got a set of screwdrivers and sit at a computer and program.” Such comments can deeply affect a person, Dr. Odom said. “Sometimes I feel that if I don’t go into the workshop and open up a bit of kit that I am not an engineer, but it’s so unconscious, it carries on with you.” These types of stories need to be told so then they can be properly addressed when they do happen, she said.
Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.
“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.
“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”
Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.
All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.
“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.
Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”
No financial disclosures were reported by any of the speakers quoted.
SOURCE: Lancet. 2019;393:493–610, e6-e28
LONDON –
“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.
“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”
For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.
Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.
“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”
Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.
“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”
Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.
That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).
“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.
Women’s credentials and capabilities were often felt to be less respected by male colleagues, and there was talk of being met with microaggressions in the workplace, as in one example given by Nana Odom, MSc, a clinical engineer at the Royal United Hospital Bath (England). She was told “you’re not an engineer, because I have not got a set of screwdrivers and sit at a computer and program.” Such comments can deeply affect a person, Dr. Odom said. “Sometimes I feel that if I don’t go into the workshop and open up a bit of kit that I am not an engineer, but it’s so unconscious, it carries on with you.” These types of stories need to be told so then they can be properly addressed when they do happen, she said.
Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.
“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.
“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”
Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.
All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.
“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.
Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”
No financial disclosures were reported by any of the speakers quoted.
SOURCE: Lancet. 2019;393:493–610, e6-e28
FROM A LAUNCH EVENT HELD BY THE LANCET
ICYMI: Andexanet alfa reduces anti–factor Xa activity from apixaban, rivaroxaban
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).
We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
What I learned from Navy SEALs about resilience
In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”
The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.
My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.
I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!
I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.
In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.
I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.
I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.
When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.
Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.
I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.
My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.
When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.
With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.
Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.
Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.
I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.
One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.
Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.
In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”
The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.
My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.
I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!
I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.
In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.
I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.
I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.
When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.
Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.
I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.
My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.
When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.
With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.
Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.
Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.
I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.
One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.
Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.
In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”
The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.
My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.
I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!
I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.
In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.
I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.
I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.
When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.
Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.
I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.
My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.
When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.
With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.
Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.
Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.
I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.
One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.
Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.
When to suspect a severe skin reaction to an AED
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
NEW ORLEANS – Most skin eruptions in patients taking antiepileptic drugs (AEDs) are relatively benign. With close supervision, some patients with epilepsy may continue treatment despite having a benign drug rash, according to a lecture at the annual meeting of the American Epilepsy Society.
“When do you know that you’re not dealing with that kind of eruption?” said Jeanne M. Young, MD, assistant professor of dermatology at the University of Virginia in Charlottesville.
Signs and symptoms that raise concerns about severe cutaneous reactions include swelling of the face; lesions that are fluid-filled, dusky, or painful; mucus membrane involvement; and signs of systemic involvement.
Associations with anticonvulsants
Diffuse swelling of the face is a hallmark symptom of DRESS. Fluid-filled lesions such as pustules, vesicles, and bullae indicate a condition other than a benign drug eruption. Signs of systemic involvement may include fever, marked eosinophilia, transaminitis, and evidence of lymphocyte activation. “In general, I want to see systemic involvement that can’t be explained by the patient’s other systemic diseases,” Dr. Young said.
A 2018 study found that AEDs are associated with SJS and TEN, and the labels for lamotrigine and carbamazepine include black box warnings about the risk of severe cutaneous adverse events. Carbamazepine’s warning, which was added in 2007, notes that SJS and TEN are significantly more common in patients of Asian ancestry with the human leukocyte antigen allele HLA-B*1502 and that physicians should screen at-risk patients before starting treatment.
Benign drug rashes
Morbilliform drug eruptions, sometimes called benign exanthems, are “by far the most common drug rash that we see” and typically are “the rashes that people refer to as drug rashes,” Dr. Young said. The mechanisms appear to be primarily immune complex mediated and cell mediated. “When the drug is stopped, these rashes tend to go away quite predictably in 2-3 weeks.”
For any class of drug, about 1% of people taking that medication may have this type of reaction, Dr. Young said. “We expect to see erythematous papules and plaques that oftentimes become confluent on the skin.” These reactions generally occur 7-10 days after the first exposure to the medication, and most patients do not have other symptoms, although the rash may itch. In addition, patients may have erythroderma with desquamation. “I think it’s important to point out the difference between desquamation, which is loss of the stratum corneum, and epidermal sloughing, which is what you see in something like [SJS] or TEN, where you’re actually losing the entire epidermis,” Dr. Young said. Recovering from desquamation is “sort of like recovering from a sun burn, and it’s not particularly dangerous.” Management of morbilliform drug eruptions is largely symptomatic.
Treat through, taper, or rechallenge
In the case a benign drug rash, “if you feel like you … need to keep a patient on a drug, you do have that option with close supervision,” Dr. Young said. “Communicate that with the dermatologist. Say, ‘I have really struggled getting this patient stabilized. Can we keep them on this drug?’ ”
The dermatologist may not fully realize the implications of stopping an effective AED in a patient with seizures that have been difficult to control. If the drug rash is benign, treating through may be an option. Patients often resolve the rash while continuing the medication, which may be because of desensitization, Dr. Young said. If a patient’s symptoms are too great to continue the drug, neurologists have the option of slowly tapering the drug and reinitiating with a new drug, Dr. Young said. Neurologists also may choose to rechallenge.
If a patient is on several medications, making it difficult to elucidate a causative agent, after stopping those drugs and allowing the rash to resolve, “there is little danger in restarting a medication,” she said.
Benign rash or DRESS?
“When I see a morbilliform eruption, usually what’s on my mind is, ‘Is this just a drug rash or is this DRESS?’ ” Dr. Young said. DRESS often starts with a morbilliform eruption that is indistinguishable from a benign drug eruption.
“Timing is a major difference,” she said. “If a patient develops a morbilliform drug eruption much later than I would expect, then my suspicion [for DRESS] goes up.” Patients with DRESS often have fever and systemic symptoms. Proposed DRESS diagnostic criteria can be useful, but clinical judgment still plays a key role. If a patient does not satisfy diagnostic criteria but has some signs and is taking a drug that is associated with DRESS, “it is going to make me more suspicious and maybe make me recommend stopping that drug sooner,” she said. Anticonvulsants such as carbamazepine, lamotrigine, and phenobarbital are among the drugs most commonly associated with DRESS.
Toxic erythemas
Patients may present with toxic erythemas, such as fixed drug reactions, erythema multiforme, SJS, and TEN. These drug reactions appear similar on biopsy but have different courses.
A patient with a fixed drug reaction often has a single lesion, and the lesion will occur in the same location every time the patient is exposed to the drug. Patients may develop additional lesions with subsequent exposures. These lesions typically are large, erythematous, well-demarcated plaques with central duskiness. “They can be bullous in the center, and they typically will heal with pigmentation, which is unique to this particular drug reaction,” said Dr. Young. “When it gets more concerning and most important to differentiate is when you get generalized bullous fixed drug eruption.” Generalized bullous fixed drug eruptions mimic and are difficult to clinically distinguish from TEN, which has a much has a much poorer prognosis.
Patients with a fixed drug eruption are not as ill as patients with TEN and tend not to slough their skin to the extent seen with TEN. Interferon gamma, perforin, and Fas ligand have been implicated as mechanisms involved in fixed drug reactions. Unlike in TEN, regulatory T cells are abundant, which may explain why TEN and fixed drug reactions progress differently even though they appear to share pathologic mechanisms, Dr. Young said.
Erythema multiforme generally presents with classic target lesions and little mucosal involvement. Infections, most commonly herpes simplex virus (HSV) 1 and 2, may trigger erythema multiforme. Dr. Young recommends evaluating patients for HSV and checking serologies, even if patients have never had a herpes outbreak. “If you have no evidence for infection, you do have to consider discontinuing a medication,” she said.
Stevens–Johnson syndrome and TEN
SJS and TEN are “the rarest of the severe cutaneous adverse drug reactions” and have “the highest morbidity and mortality,” Dr. Young said. They appear to exist on a continuum where SJS may represent early TEN.
“This is a situation where you expect to see blistering of the skin [and] always mucosal involvement. You need to stop the drug immediately when you suspect this drug reaction,” Dr. Young said.
One reason to distinguish SJS or early TEN from later TEN is that high-dose steroids may play a role in the treatment of SJS or early TEN. “Once you get past about 10% total body surface area, there is good evidence that steroids actually increase morbidity and mortality,” she said.
If the eruption has occurred before, that factor suggests that a diagnosis of erythema multiforme or fixed drug reaction may be more likely than TEN.
An apparent lack of regulatory T cells in TEN could explain why patients with HIV infection are at much higher risk of developing SJS and TEN. Understanding the role that regulatory T cells play in severe drug eruptions may lead to new therapeutic options in the future, Dr. Young said.
Dr. Young had no disclosures.
EXPERT ANALYSIS FROM AES 2018
Minimally invasive ICH lysis safely helps when clot adequately shrinks
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
REPORTING FROM ISC 2019
Key clinical point: Minimally-invasive intracerebral clot lysis was safe and often effective when the residual clot shrank to 15 mL or less.
Major finding: One year after entry, 45% of MISTIE-treated patients and 41% of controls had a modified Rankin Scale score of 0-3.
Study details: MISTIE III, a multicenter, international, randomized trial of 499 patients.
Disclosures: MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
Source: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
500 Women in Medicine: Part II
Ms. Gerull and Ms. Loe are third-year medical students at Washington University School of Medicine in St. Louis. According to Gerull and Loe, the aim is to create a network of support and advancement for women in medicine. 500 Women in Medicine is a pod of the organization 500 Women Scientists.
Apple Podcasts
Google Podcasts
Spotify
Ms. Gerull and Ms. Loe are third-year medical students at Washington University School of Medicine in St. Louis. According to Gerull and Loe, the aim is to create a network of support and advancement for women in medicine. 500 Women in Medicine is a pod of the organization 500 Women Scientists.
Apple Podcasts
Google Podcasts
Spotify
Ms. Gerull and Ms. Loe are third-year medical students at Washington University School of Medicine in St. Louis. According to Gerull and Loe, the aim is to create a network of support and advancement for women in medicine. 500 Women in Medicine is a pod of the organization 500 Women Scientists.
Apple Podcasts
Google Podcasts
Spotify
Intranasal esketamine gets FDA support for refractory depression
Also today, the office of the National Coordinator of Health Information Technology aims to help doctors and patients with information sharing, most physicians think that health care costs and access are unlikely to improve in 2019, and vaccination and antiviral treatment do not affect the risk of stroke following shingles.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, the office of the National Coordinator of Health Information Technology aims to help doctors and patients with information sharing, most physicians think that health care costs and access are unlikely to improve in 2019, and vaccination and antiviral treatment do not affect the risk of stroke following shingles.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, the office of the National Coordinator of Health Information Technology aims to help doctors and patients with information sharing, most physicians think that health care costs and access are unlikely to improve in 2019, and vaccination and antiviral treatment do not affect the risk of stroke following shingles.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
