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Bariatric surgery may be appropriate for class 1 obesity
LAS VEGAS – Once reserved for the most obese patients, bariatric surgery is on the road to becoming an option for millions of Americans who are just a step beyond overweight, even those with a body mass index as low as 30 kg/m2.
In regard to patients with lower levels of obesity, “we should be intervening in this chronic disease earlier rather than later,” said Stacy A. Brethauer, MD, professor of surgery at the Ohio State University, Columbus, in a presentation about new standards for bariatric surgery at the 2019 Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.
Bariatric treatment “should be offered after nonsurgical [weight-loss] therapy has failed,” he said. “That’s not where you stop. You continue to escalate as you would for heart disease or cancer.”
As Dr. Brethauer noted, research suggests that all categories of obesity – including so-called class 1 obesity (defined as a BMI from 30.0 to 34.9 kg/m2) – boost the risk of multiple diseases, including hypertension, coronary artery disease, congestive heart failure, stroke, asthma, pulmonary embolism, gallbladder disease, several types of cancer, osteoarthritis, and chronic back pain.
“There is no question that class 1 obesity is clearly putting people at risk,” he said. “Ultimately, you can conclude from all this evidence that class 1 is a chronic disease, and it deserves to be treated effectively.”
There are, of course, various nonsurgical treatments for obesity, including diet and exercise and pharmacotherapy. However, systematic reviews have found that people find it extremely difficult to keep the weight off after 1 year regardless of the strategy they adopt.
Beyond a year, Dr. Brethauer said, “you get poor maintenance of weight control, and you get poor control of metabolic burden. You don’t have a durable efficacy.”
In the past, bariatric surgery wasn’t considered an option for patients with class 1 obesity. It’s traditionally been reserved for patients with BMIs at or above 35 kg/m2. But this standard has evolved in recent years.
In 2018, Dr. Brethauer coauthored an updated position statement by the American Society for Metabolic and Bariatric Surgery that encouraged bariatric surgery in certain mildly obese patients.
“For most people with class I obesity,” the statement on bariatric surgery states, “it is clear that the nonsurgical group of therapies will not provide a durable solution to their disease of obesity.”
The statement went on to say that “surgical intervention should be considered after failure of nonsurgical treatments” in the class 1 population.
Bariatric surgery in the class 1 population does more than reduce obesity, Dr. Brethauer said. “Over the last 5 years or so, a large body of literature has emerged,” he said, and both systematic reviews and randomized trails have shown significant postsurgery improvements in comorbidities such as diabetes.
“It’s important to emphasize that these patients don’t become underweight,” he said. “The body finds a healthy set point. They don’t become underweight or malnourished because you’re operating on a lower-weight group.”
Are weight-loss operations safe in class 1 patients? The American Society for Metabolic and Bariatric Surgery statement says that research has found “bariatric surgery is associated with modest morbidity and very low mortality in patients with class I obesity.”
In fact, Dr. Brethauer said, the mortality rate in this population is “less than gallbladder surgery, less than hip surgery, less than hysterectomy, less than knee surgery – operations people are being referred for and undergoing all the time.”
He added: “The case can be made very clearly based on this data that these operations are safe in this patient population. Not only are they safe, they have durable and significant impact on comorbidities.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Brethauer discloses relationships with Medtronic (speaker) and GI Windows (consultant).
Review the AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper, which provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/WV8l30oeyYv.
LAS VEGAS – Once reserved for the most obese patients, bariatric surgery is on the road to becoming an option for millions of Americans who are just a step beyond overweight, even those with a body mass index as low as 30 kg/m2.
In regard to patients with lower levels of obesity, “we should be intervening in this chronic disease earlier rather than later,” said Stacy A. Brethauer, MD, professor of surgery at the Ohio State University, Columbus, in a presentation about new standards for bariatric surgery at the 2019 Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.
Bariatric treatment “should be offered after nonsurgical [weight-loss] therapy has failed,” he said. “That’s not where you stop. You continue to escalate as you would for heart disease or cancer.”
As Dr. Brethauer noted, research suggests that all categories of obesity – including so-called class 1 obesity (defined as a BMI from 30.0 to 34.9 kg/m2) – boost the risk of multiple diseases, including hypertension, coronary artery disease, congestive heart failure, stroke, asthma, pulmonary embolism, gallbladder disease, several types of cancer, osteoarthritis, and chronic back pain.
“There is no question that class 1 obesity is clearly putting people at risk,” he said. “Ultimately, you can conclude from all this evidence that class 1 is a chronic disease, and it deserves to be treated effectively.”
There are, of course, various nonsurgical treatments for obesity, including diet and exercise and pharmacotherapy. However, systematic reviews have found that people find it extremely difficult to keep the weight off after 1 year regardless of the strategy they adopt.
Beyond a year, Dr. Brethauer said, “you get poor maintenance of weight control, and you get poor control of metabolic burden. You don’t have a durable efficacy.”
In the past, bariatric surgery wasn’t considered an option for patients with class 1 obesity. It’s traditionally been reserved for patients with BMIs at or above 35 kg/m2. But this standard has evolved in recent years.
In 2018, Dr. Brethauer coauthored an updated position statement by the American Society for Metabolic and Bariatric Surgery that encouraged bariatric surgery in certain mildly obese patients.
“For most people with class I obesity,” the statement on bariatric surgery states, “it is clear that the nonsurgical group of therapies will not provide a durable solution to their disease of obesity.”
The statement went on to say that “surgical intervention should be considered after failure of nonsurgical treatments” in the class 1 population.
Bariatric surgery in the class 1 population does more than reduce obesity, Dr. Brethauer said. “Over the last 5 years or so, a large body of literature has emerged,” he said, and both systematic reviews and randomized trails have shown significant postsurgery improvements in comorbidities such as diabetes.
“It’s important to emphasize that these patients don’t become underweight,” he said. “The body finds a healthy set point. They don’t become underweight or malnourished because you’re operating on a lower-weight group.”
Are weight-loss operations safe in class 1 patients? The American Society for Metabolic and Bariatric Surgery statement says that research has found “bariatric surgery is associated with modest morbidity and very low mortality in patients with class I obesity.”
In fact, Dr. Brethauer said, the mortality rate in this population is “less than gallbladder surgery, less than hip surgery, less than hysterectomy, less than knee surgery – operations people are being referred for and undergoing all the time.”
He added: “The case can be made very clearly based on this data that these operations are safe in this patient population. Not only are they safe, they have durable and significant impact on comorbidities.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Brethauer discloses relationships with Medtronic (speaker) and GI Windows (consultant).
Review the AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper, which provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/WV8l30oeyYv.
LAS VEGAS – Once reserved for the most obese patients, bariatric surgery is on the road to becoming an option for millions of Americans who are just a step beyond overweight, even those with a body mass index as low as 30 kg/m2.
In regard to patients with lower levels of obesity, “we should be intervening in this chronic disease earlier rather than later,” said Stacy A. Brethauer, MD, professor of surgery at the Ohio State University, Columbus, in a presentation about new standards for bariatric surgery at the 2019 Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.
Bariatric treatment “should be offered after nonsurgical [weight-loss] therapy has failed,” he said. “That’s not where you stop. You continue to escalate as you would for heart disease or cancer.”
As Dr. Brethauer noted, research suggests that all categories of obesity – including so-called class 1 obesity (defined as a BMI from 30.0 to 34.9 kg/m2) – boost the risk of multiple diseases, including hypertension, coronary artery disease, congestive heart failure, stroke, asthma, pulmonary embolism, gallbladder disease, several types of cancer, osteoarthritis, and chronic back pain.
“There is no question that class 1 obesity is clearly putting people at risk,” he said. “Ultimately, you can conclude from all this evidence that class 1 is a chronic disease, and it deserves to be treated effectively.”
There are, of course, various nonsurgical treatments for obesity, including diet and exercise and pharmacotherapy. However, systematic reviews have found that people find it extremely difficult to keep the weight off after 1 year regardless of the strategy they adopt.
Beyond a year, Dr. Brethauer said, “you get poor maintenance of weight control, and you get poor control of metabolic burden. You don’t have a durable efficacy.”
In the past, bariatric surgery wasn’t considered an option for patients with class 1 obesity. It’s traditionally been reserved for patients with BMIs at or above 35 kg/m2. But this standard has evolved in recent years.
In 2018, Dr. Brethauer coauthored an updated position statement by the American Society for Metabolic and Bariatric Surgery that encouraged bariatric surgery in certain mildly obese patients.
“For most people with class I obesity,” the statement on bariatric surgery states, “it is clear that the nonsurgical group of therapies will not provide a durable solution to their disease of obesity.”
The statement went on to say that “surgical intervention should be considered after failure of nonsurgical treatments” in the class 1 population.
Bariatric surgery in the class 1 population does more than reduce obesity, Dr. Brethauer said. “Over the last 5 years or so, a large body of literature has emerged,” he said, and both systematic reviews and randomized trails have shown significant postsurgery improvements in comorbidities such as diabetes.
“It’s important to emphasize that these patients don’t become underweight,” he said. “The body finds a healthy set point. They don’t become underweight or malnourished because you’re operating on a lower-weight group.”
Are weight-loss operations safe in class 1 patients? The American Society for Metabolic and Bariatric Surgery statement says that research has found “bariatric surgery is associated with modest morbidity and very low mortality in patients with class I obesity.”
In fact, Dr. Brethauer said, the mortality rate in this population is “less than gallbladder surgery, less than hip surgery, less than hysterectomy, less than knee surgery – operations people are being referred for and undergoing all the time.”
He added: “The case can be made very clearly based on this data that these operations are safe in this patient population. Not only are they safe, they have durable and significant impact on comorbidities.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Brethauer discloses relationships with Medtronic (speaker) and GI Windows (consultant).
Review the AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper, which provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/WV8l30oeyYv.
REPORTING FROM MISS
FDA approves multiple ambrisentan generics for patients with PAH
The Food and Drug Administration has approved multiple generics for ambrisentan (Letairis) tablets, as well as their associated risk evaluation and mitigation strategies (REMS), for patients with pulmonary arterial hypertension.
A total of four generics were approved, licensed to Mylan Pharmaceuticals, Sun Pharma Global, Watson Laboratories, and Zydus Pharmaceuticals. All four were approved at 5-mg and 10-mg doses. According to the label, the most common adverse events associated with ambrisentan include peripheral edema, nasal congestion, sinusitis, and flushing.
In addition to the generics, the FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, includes the brand sponsor and three abbreviated new drug applications. The FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, is composed of the brand sponsor and three abbreviated new drug applications. The second, PS-Ambrisentan REMS, is a parallel system and currently is constituted by one abbreviated new drug application.
“With the approval of these first generics ... patients will now have access to additional products (brand-name and generic) and additional types of pharmacies to fill their prescriptions,” the FDA said.
Find the full press release on the FDA website.
The Food and Drug Administration has approved multiple generics for ambrisentan (Letairis) tablets, as well as their associated risk evaluation and mitigation strategies (REMS), for patients with pulmonary arterial hypertension.
A total of four generics were approved, licensed to Mylan Pharmaceuticals, Sun Pharma Global, Watson Laboratories, and Zydus Pharmaceuticals. All four were approved at 5-mg and 10-mg doses. According to the label, the most common adverse events associated with ambrisentan include peripheral edema, nasal congestion, sinusitis, and flushing.
In addition to the generics, the FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, includes the brand sponsor and three abbreviated new drug applications. The FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, is composed of the brand sponsor and three abbreviated new drug applications. The second, PS-Ambrisentan REMS, is a parallel system and currently is constituted by one abbreviated new drug application.
“With the approval of these first generics ... patients will now have access to additional products (brand-name and generic) and additional types of pharmacies to fill their prescriptions,” the FDA said.
Find the full press release on the FDA website.
The Food and Drug Administration has approved multiple generics for ambrisentan (Letairis) tablets, as well as their associated risk evaluation and mitigation strategies (REMS), for patients with pulmonary arterial hypertension.
A total of four generics were approved, licensed to Mylan Pharmaceuticals, Sun Pharma Global, Watson Laboratories, and Zydus Pharmaceuticals. All four were approved at 5-mg and 10-mg doses. According to the label, the most common adverse events associated with ambrisentan include peripheral edema, nasal congestion, sinusitis, and flushing.
In addition to the generics, the FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, includes the brand sponsor and three abbreviated new drug applications. The FDA also approved two shared system REMS programs for ambrisentan. The first, Ambrisentan REMS, is composed of the brand sponsor and three abbreviated new drug applications. The second, PS-Ambrisentan REMS, is a parallel system and currently is constituted by one abbreviated new drug application.
“With the approval of these first generics ... patients will now have access to additional products (brand-name and generic) and additional types of pharmacies to fill their prescriptions,” the FDA said.
Find the full press release on the FDA website.
Anti-EGFR TKI, MET inhibitor team up against drug-resistant NSCLC
ATLANTA – About 10%-25% of patients with epithelial growth factor receptor–(EGFR) mutant non–small cell lung cancer (NSCLC) have tumors with either MET amplification or another MET-based mechanism that leads to drug resistance.
In the TATTON trial, investigators are evaluating a combination of the EGFR-targeted tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, for safety and activity against MET-driven NSCLC in patients with disease that has progressed on one or more prior EGFR-targeted agents.
In a video interview at the annual meeting of the American Association for Cancer Research, Lecia Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston, discusses early results with the osimertinib/savolitinib combination in patients with disease progression after a first and/or second-generation EGFR TKI, or after a third-generation agent.
Dr. Sequist said results of TATTON suggest that it may be possible to overcome MET-driven drug-resistance mechanisms.
The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company.
ATLANTA – About 10%-25% of patients with epithelial growth factor receptor–(EGFR) mutant non–small cell lung cancer (NSCLC) have tumors with either MET amplification or another MET-based mechanism that leads to drug resistance.
In the TATTON trial, investigators are evaluating a combination of the EGFR-targeted tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, for safety and activity against MET-driven NSCLC in patients with disease that has progressed on one or more prior EGFR-targeted agents.
In a video interview at the annual meeting of the American Association for Cancer Research, Lecia Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston, discusses early results with the osimertinib/savolitinib combination in patients with disease progression after a first and/or second-generation EGFR TKI, or after a third-generation agent.
Dr. Sequist said results of TATTON suggest that it may be possible to overcome MET-driven drug-resistance mechanisms.
The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company.
ATLANTA – About 10%-25% of patients with epithelial growth factor receptor–(EGFR) mutant non–small cell lung cancer (NSCLC) have tumors with either MET amplification or another MET-based mechanism that leads to drug resistance.
In the TATTON trial, investigators are evaluating a combination of the EGFR-targeted tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, for safety and activity against MET-driven NSCLC in patients with disease that has progressed on one or more prior EGFR-targeted agents.
In a video interview at the annual meeting of the American Association for Cancer Research, Lecia Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston, discusses early results with the osimertinib/savolitinib combination in patients with disease progression after a first and/or second-generation EGFR TKI, or after a third-generation agent.
Dr. Sequist said results of TATTON suggest that it may be possible to overcome MET-driven drug-resistance mechanisms.
The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company.
REPORTING FROM AACR 2019
CAR T cells target HER2 expression in advanced sarcomas
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
ATLANTA – Sarcomas of bone and soft tissues are considered to be “antigenically cold” tumors, with few identifiable mutations that may be susceptible to targeted therapies.
Some sarcoma subtypes such as osteosarcoma and rhabomyosarcoma, however, frequently express the human epidermal growth factor receptor 2 on tumor surfaces. Although HER2 expression in these tumors is at too low a level for HER2-targeted therapies such as trastuzumab (Herceptin), HER2 appears to be an opportunistic target for chimeric antigen receptor (CAR) T-cell therapy, according to Shoba Navai, MD, from Baylor College of Medicine, Houston.
In a video interview at the 2019 annual meeting of the American Association for Cancer Research, Dr. Navai describes her team’s early experience using a HER2-targeted CAR-T cell construct and preinfusion lymphodepletion in patients with advanced sarcomas.
Development of the CAR-T cell construct is supported by the Cancer Prevention & Research Institute of Texas, Stand Up to Cancer, the St. Baldrick’s Foundation, Cookies for Kids’ Cancer, Alex’s Lemonade Stand, and a grant from the National Institutes of Health. Dr. Navai reported having no disclosures.
REPORTING FROM AACR 2019
FDA approves Mavenclad for treatment of relapsing MS
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
including relapsing/remitting and active secondary progressive disease.
The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.
The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.
The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.
“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.
The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.
Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.
Fundamentals of Gene Therapy: Addressing Gaps in Physician Education
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
Click here to read supplement.
Gene therapy is a contemporary therapeutic intervention with recent positive results and regulatory approvals either completed or expected in the next several years for various conditions. In this supplement, learn more about:
- Basic principles of gene therapy
- In vivo vs ex vivo methods of gene transfer
- Vector types
- Clinical Considerations
About the Author
Click here to read supplement.
PA Specific Program Scheduled for VAM
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
The PA Section steering committee has been hard at work developing session programming for the 2019 Vascular Annual Meeting. Vascular PAs can look forward to a four-hour session on Thursday, June 13, completely dedicated to them. The program will focus on a variety of topics that include optimal team practice, vascular diagnostics, venous disease and wound management, an “Ask the Expert” portion and much more. Know a vascular PA who needs to become an SVS member? Encourage them to apply today.
SVSConnect – Save the Date!
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
The SVS is excited to announce that within your online community, SVSConnect, there will be an “Ask Us Anything” session at 2 p.m. CDT on April 8. Drs. Daniel McDevitt and William Shutze will be available in real time to answer questions about building relationships in a competitive environment. SVSConnect users will be able to chime in during the session to ask them anything. If you can’t make it to the live Q&A on April 8, all the questions and responses will be available in the SVSConnect library. More information will come soon.
Reframing the conversation around the ‘gender-reveal’ ultrasound
How revealing fetal anatomy, not gender, is inclusive
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
How revealing fetal anatomy, not gender, is inclusive
How revealing fetal anatomy, not gender, is inclusive
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
Every ob.gyn. expects that the topic of gender will come up at some point in a patient’s pregnancy. “When will I find out the gender?” asks the 24-year-old at her first prenatal visit. “We want the gender to be a surprise!” exclaims the couple at their anatomy scan for their second in vitro fertilization pregnancy. “Do you know what you’re having?” asks the obstetrician anticipating an imminent delivery.
The topic of gender is in fact so ingrained in our practice that we don’t bat an eye when approached with questions about fetal gender. But what exactly are we talking about when we discuss the gender of an unborn baby?
As we established in our previous column, gender identity is an internal experience of gender that one feels to be a part of oneself. So, then, what does an ultrasound actually reveal? Objectively, ultrasound can show the provider the presence or absence of a hyperechoic anatomical structure between the fetal legs that may become a penis, a vagina, or an ambiguous form of genitalia. While ultrasound is an incredible tool for anatomical and other forms of antenatal testing, ultrasound cannot detect identity characteristics because identities are, by definition, socially and internally experienced without respect to anatomy.
The distinction between gender identity and sex assigned at birth in discussions of antenatal ultrasonography is more than just a simple problem of semantics or vocabulary. To describe a fetus as a boy or a girl based on the presence/absence of a projection between the fetal legs seen on ultrasound is to reinforce the idea that gender identity and sex assigned at birth are equivalent. This conflation also erases nonbinary, genderqueer, and many other groups that identify with genders other than “boy” or “girl.” To be clear, unborn fetuses do not have a gender identity. Studies have shown that children begin to self-label their gender as early as 18-24 months of age, and similarly those who grow up to inhabit gender-nonconforming identities usually already are starting to show signs of their nonconformity starting at age 2 years.1 Some of the deepest traumas that trans and gender-nonconforming people experience are rated to the enforcement of unwritten gender laws during early childhood that are applied based on the sex assigned at birth.
Obstetricians can help to break the cycle of inappropriate gender assignment by correctly using the terms “gender” and “sex assigned at birth.” One opportunity for addressing patients’ questions about fetal gender might be to avoid the term “gender” altogether when discussing fetal sex assigned at birth, emphasizing instead what fetal ultrasound is actually able to do: Give us information about the appearance of external genitalia to help predict what sex will be assigned at birth.2 We have used this strategy when performing anatomy scans, and our experience has been that patients often will make their own assumptions about what it means to see certain external genitalia on ultrasound between the fetal legs. Motivated providers who want to go the extra mile may use a patient’s exclamation about their understanding of the fetus’s gender as an opportunity to educate the patient on the distinction between gender and sex assigned at birth, but even just smiling and moving onto the next part of the scan is an appropriate way of maintaining an atmosphere of inclusion and respect.
One of the roots of gender-based violence and gender dysphoria later in life is the conflation of gender and sex assigned at birth. While there is an entire social and political framework that enforces and polices gender after birth, the obstetrician can take steps to break the cycle starting before the birth has even occurred. Obstetricians are tasked with the unique challenge of providing care for the mother-fetus dyad, and much of the work is in setting up the fetus for the best possible life. Our scope of inclusion should be sufficiently wide to account for nonanatomical variations that could develop later in life in the infants we deliver.
Dr. Bahng is a PGY-1 resident physician in the gynecology & obstetrics residency program at Emory University, Atlanta. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner is an assistant professor at Emory University and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Bahng and Dr. Joyner reported no financial disclosures.
References
1. Horm Behav. 2013 Jul;64(2):288-97.
2. Obstet Gynecol Surv. 2009 Jan;64(1):50-7.
Valproate, topiramate prescribed in young women despite known teratogenicity risks
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
FROM JAMA NEUROLOGY
Key clinical point: Both valproate and topiramate are prescribed relatively often in women of childbearing age despite known teratogenic risks.
Major finding: Topiramate was the second- or third-most prescribed AED in the analyses. Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy.
Study details: Retrospective cohort study including nearly 47,000 women of childbearing age enrolled in claims databases between 2009 and 2013.
Disclosures: UCB Pharma sponsored the study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
Source: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.