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Screening criteria for diabetes in youth won’t capture all at high risk
and therefore “may miss high-risk youth who should be targeted for diabetes prevention,” according to the investigators of a cross-sectional analysis of youth in the 1999-2016 National Health and Nutrition Examination Survey (NHANES) database.
Regardless of whether or not youth meet screening eligibility, they say, hemoglobin A1c appears to be a “specific and useful test” for detecting high-risk youth.
Those with prediabetic levels of A1c or fasting plasma glucose (FPG) – A1c especially – had a high burden of other cardiometabolic risk factors that could benefit from lifestyle interventions to prevent diabetes and cardiovascular risk in adulthood, wrote Amelia S. Wallace and coinvestigators at the Johns Hopkins Bloomberg School of Public Health, Baltimore. The report is in Pediatrics.Their epidemiologic study had two aims: To assess the performance of the American Diabetes Association guidelines for screening in youth, and to evaluate how well various clinical definitions of diabetes and prediabetes identify U.S. youth at high cardiometabolic risk.
The 2018 ADA guidelines recommend screening for type 2 diabetes and prediabetes in all asymptomatic youth ages 10 years and older who are overweight or obese and who have at least one risk factor for diabetes: nonwhite race, family history of type 2 diabetes, maternal gestational diabetes, or signs of insulin resistance or conditions associated with insulin resistance (Diabetes Care. 2018:41[suppl 1:S13-S37]).
Approximately one-quarter of U.S. youth were found to be eligible for screening under the current ADA criteria, but there were few cases of confirmed diabetes (A1c greater than or equal to 6.5% and fasting plasma glucose greater than or equal to 126 mg/dL) that had gone undiagnosed (less than 0.5%), said Ms. Wallace and her associates.
Considering all hyperglycemia (undiagnosed diabetes or prediabetes) in the NHANES youth population, the sensitivity and specificity of the ADA criteria for detecting A1c-defined hyperglycemia (greater than or equal to 5.7%) were 56% and 76%, respectively, and the sensitivity and specificity for detecting FBG-defined hyperglycemia (greater than or equal to 100 mg/dL) were 36% and 77%.
The prevalence of any hyperglycemia was higher in youth who met ADA screening criteria than in those who didn’t, but there were also “a substantial number of youth with hyperglycemia in the non–screening eligible population,” they wrote. “In fact, the absolute number of youth with elevated FPG was larger in the non–screening eligible population, and the majority (88.5%) of these youth were of normal weight.”
Across all youth (irrespective of screening eligibility), both FPG and A1c-defined hyperglycemia effectively identified children and adolescents who had a high burden of cardiometabolic risk (obesity, metabolic syndrome, and hypercholesterolemia). Using a confirmatory definition of elevations in both FPG and A1c “provided the highest discrimination for cardiometabolic risk,” Ms. Wallace and her associates said.
But in comparing the single tests, risk factor associations with hyperglycemia were consistently stronger with A1c-defined hyperglycemia (odds ratios of 2.6-4.1) than FBG-defined hyperglycemia (ORs of 1.5-3.0). A1c-defined hyperglycemia “identifies a smaller, but higher-risk, population than FPG-defined hyperglycemia,” they said.
In an accompanying commentary, Tamara S. Hannon, MD, MS, of the division of pediatric endocrinology and diabetology at Indiana University in Indianapolis, said that more effective algorithms to determine who should have laboratory testing “could be useful.” Still, “for youth with obesity and multiple risk factors for developing type 2 diabetes, the principal challenge is how to effectively prevent or delay this disease for them and future generations.”
Pediatricians, she said, should screen for prediabetes and type 2 diabetes “according to professional recommendations with simple clinical tests, such as A1c. Screening and education about prediabetes alone can lead to better rates of follow-up for obesity,” she noted (Pediatrics. August 2020. doi: 10.1542/peds.2020-010272).
Sheela N. Magge, MD, MSCE, who directs the division of pediatric endocrinology and diabetes at John Hopkins University, Baltimore, and was asked to comment on the study, similarly said that the findings should not discourage use of the ADA guidelines.
While the guidelines may not have optimal sensitivity and specificity, “neither HbA1c nor fasting glucose are perfect screening tools for prediabetes and likely give us different mechanistic information,” she said. (The ADA guidelines also allow the use of a 2-hour oral glucose tolerance test, but this is not often used by pediatricians, she noted.)
The measurements are “only tools used to identify children who have prediabetes and are therefore at increased risk for type 2 diabetes,” said Dr. Magge, the Lawson Wilkins Endowed Chair of Pediatric Endocrinology at the university. “These children then need to be managed and followed to try to prevent worsening glycemia.”
Both she and Dr. Hannon stressed that youth with type 2 diabetes have more rapidly progressive disease compared with adults.
Microvascular complications are seen even at diagnosis, Dr. Magge said, and “youth may face serious complications such as cardiovascular disease decades earlier than previous generations.”
Dr. Hannon also noted in her commentary that oral diabetes medications often fail in youth with type 2 diabetes, leading to insulin therapy early on.
The prevalence of youth-onset type 2 diabetes has increased because of rising rates of pediatric overweight and obesity, Dr. Magge emphasized. In her experience, the diabetes risk factors that guide the ADA’s screening approach “are so common in overweight and obese youth that they all have at least one.”
The NHANES data did not contain information on all the variables that make up the current diabetes screening criteria in youth; there was no explicit information on history of maternal gestational diabetes and family history of type 2 diabetes, for instance, or the presence of acanthosis nigricans or polycystic ovarian syndrome – conditions associated with insulin resistance. The investigators said it’s likely, therefore, that the study underestimated the number of U.S. youth who would be eligible for diabetes screening.
And, as Dr. Magge said, “it is difficult to determine which risk factors [in the ADA guidelines] were less predictive.”
The NHANES analysis covered 14,119 youth in the 1999-2016 NHANES surveys, which consisted of interviews and standardized physical exams, including laboratory tests, in home and at a mobile examination center. Analyses involving any fasting lab tests were limited to a random subsample of participants aged 12-19 years without diagnosed diabetes who were asked to fast the night before; 6,225 youth properly followed instructions and were included in this subsample.
The surveys are conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. The study authors and the editorial author indicated that they have no relevant financial disclosures or conflicts of interest. Dr. Magge also said she has no relevant disclosures.
SOURCE: Wallace AS et al. Pediatrics. August 2020. doi: 10.1542/peds.2020-0265.
and therefore “may miss high-risk youth who should be targeted for diabetes prevention,” according to the investigators of a cross-sectional analysis of youth in the 1999-2016 National Health and Nutrition Examination Survey (NHANES) database.
Regardless of whether or not youth meet screening eligibility, they say, hemoglobin A1c appears to be a “specific and useful test” for detecting high-risk youth.
Those with prediabetic levels of A1c or fasting plasma glucose (FPG) – A1c especially – had a high burden of other cardiometabolic risk factors that could benefit from lifestyle interventions to prevent diabetes and cardiovascular risk in adulthood, wrote Amelia S. Wallace and coinvestigators at the Johns Hopkins Bloomberg School of Public Health, Baltimore. The report is in Pediatrics.Their epidemiologic study had two aims: To assess the performance of the American Diabetes Association guidelines for screening in youth, and to evaluate how well various clinical definitions of diabetes and prediabetes identify U.S. youth at high cardiometabolic risk.
The 2018 ADA guidelines recommend screening for type 2 diabetes and prediabetes in all asymptomatic youth ages 10 years and older who are overweight or obese and who have at least one risk factor for diabetes: nonwhite race, family history of type 2 diabetes, maternal gestational diabetes, or signs of insulin resistance or conditions associated with insulin resistance (Diabetes Care. 2018:41[suppl 1:S13-S37]).
Approximately one-quarter of U.S. youth were found to be eligible for screening under the current ADA criteria, but there were few cases of confirmed diabetes (A1c greater than or equal to 6.5% and fasting plasma glucose greater than or equal to 126 mg/dL) that had gone undiagnosed (less than 0.5%), said Ms. Wallace and her associates.
Considering all hyperglycemia (undiagnosed diabetes or prediabetes) in the NHANES youth population, the sensitivity and specificity of the ADA criteria for detecting A1c-defined hyperglycemia (greater than or equal to 5.7%) were 56% and 76%, respectively, and the sensitivity and specificity for detecting FBG-defined hyperglycemia (greater than or equal to 100 mg/dL) were 36% and 77%.
The prevalence of any hyperglycemia was higher in youth who met ADA screening criteria than in those who didn’t, but there were also “a substantial number of youth with hyperglycemia in the non–screening eligible population,” they wrote. “In fact, the absolute number of youth with elevated FPG was larger in the non–screening eligible population, and the majority (88.5%) of these youth were of normal weight.”
Across all youth (irrespective of screening eligibility), both FPG and A1c-defined hyperglycemia effectively identified children and adolescents who had a high burden of cardiometabolic risk (obesity, metabolic syndrome, and hypercholesterolemia). Using a confirmatory definition of elevations in both FPG and A1c “provided the highest discrimination for cardiometabolic risk,” Ms. Wallace and her associates said.
But in comparing the single tests, risk factor associations with hyperglycemia were consistently stronger with A1c-defined hyperglycemia (odds ratios of 2.6-4.1) than FBG-defined hyperglycemia (ORs of 1.5-3.0). A1c-defined hyperglycemia “identifies a smaller, but higher-risk, population than FPG-defined hyperglycemia,” they said.
In an accompanying commentary, Tamara S. Hannon, MD, MS, of the division of pediatric endocrinology and diabetology at Indiana University in Indianapolis, said that more effective algorithms to determine who should have laboratory testing “could be useful.” Still, “for youth with obesity and multiple risk factors for developing type 2 diabetes, the principal challenge is how to effectively prevent or delay this disease for them and future generations.”
Pediatricians, she said, should screen for prediabetes and type 2 diabetes “according to professional recommendations with simple clinical tests, such as A1c. Screening and education about prediabetes alone can lead to better rates of follow-up for obesity,” she noted (Pediatrics. August 2020. doi: 10.1542/peds.2020-010272).
Sheela N. Magge, MD, MSCE, who directs the division of pediatric endocrinology and diabetes at John Hopkins University, Baltimore, and was asked to comment on the study, similarly said that the findings should not discourage use of the ADA guidelines.
While the guidelines may not have optimal sensitivity and specificity, “neither HbA1c nor fasting glucose are perfect screening tools for prediabetes and likely give us different mechanistic information,” she said. (The ADA guidelines also allow the use of a 2-hour oral glucose tolerance test, but this is not often used by pediatricians, she noted.)
The measurements are “only tools used to identify children who have prediabetes and are therefore at increased risk for type 2 diabetes,” said Dr. Magge, the Lawson Wilkins Endowed Chair of Pediatric Endocrinology at the university. “These children then need to be managed and followed to try to prevent worsening glycemia.”
Both she and Dr. Hannon stressed that youth with type 2 diabetes have more rapidly progressive disease compared with adults.
Microvascular complications are seen even at diagnosis, Dr. Magge said, and “youth may face serious complications such as cardiovascular disease decades earlier than previous generations.”
Dr. Hannon also noted in her commentary that oral diabetes medications often fail in youth with type 2 diabetes, leading to insulin therapy early on.
The prevalence of youth-onset type 2 diabetes has increased because of rising rates of pediatric overweight and obesity, Dr. Magge emphasized. In her experience, the diabetes risk factors that guide the ADA’s screening approach “are so common in overweight and obese youth that they all have at least one.”
The NHANES data did not contain information on all the variables that make up the current diabetes screening criteria in youth; there was no explicit information on history of maternal gestational diabetes and family history of type 2 diabetes, for instance, or the presence of acanthosis nigricans or polycystic ovarian syndrome – conditions associated with insulin resistance. The investigators said it’s likely, therefore, that the study underestimated the number of U.S. youth who would be eligible for diabetes screening.
And, as Dr. Magge said, “it is difficult to determine which risk factors [in the ADA guidelines] were less predictive.”
The NHANES analysis covered 14,119 youth in the 1999-2016 NHANES surveys, which consisted of interviews and standardized physical exams, including laboratory tests, in home and at a mobile examination center. Analyses involving any fasting lab tests were limited to a random subsample of participants aged 12-19 years without diagnosed diabetes who were asked to fast the night before; 6,225 youth properly followed instructions and were included in this subsample.
The surveys are conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. The study authors and the editorial author indicated that they have no relevant financial disclosures or conflicts of interest. Dr. Magge also said she has no relevant disclosures.
SOURCE: Wallace AS et al. Pediatrics. August 2020. doi: 10.1542/peds.2020-0265.
and therefore “may miss high-risk youth who should be targeted for diabetes prevention,” according to the investigators of a cross-sectional analysis of youth in the 1999-2016 National Health and Nutrition Examination Survey (NHANES) database.
Regardless of whether or not youth meet screening eligibility, they say, hemoglobin A1c appears to be a “specific and useful test” for detecting high-risk youth.
Those with prediabetic levels of A1c or fasting plasma glucose (FPG) – A1c especially – had a high burden of other cardiometabolic risk factors that could benefit from lifestyle interventions to prevent diabetes and cardiovascular risk in adulthood, wrote Amelia S. Wallace and coinvestigators at the Johns Hopkins Bloomberg School of Public Health, Baltimore. The report is in Pediatrics.Their epidemiologic study had two aims: To assess the performance of the American Diabetes Association guidelines for screening in youth, and to evaluate how well various clinical definitions of diabetes and prediabetes identify U.S. youth at high cardiometabolic risk.
The 2018 ADA guidelines recommend screening for type 2 diabetes and prediabetes in all asymptomatic youth ages 10 years and older who are overweight or obese and who have at least one risk factor for diabetes: nonwhite race, family history of type 2 diabetes, maternal gestational diabetes, or signs of insulin resistance or conditions associated with insulin resistance (Diabetes Care. 2018:41[suppl 1:S13-S37]).
Approximately one-quarter of U.S. youth were found to be eligible for screening under the current ADA criteria, but there were few cases of confirmed diabetes (A1c greater than or equal to 6.5% and fasting plasma glucose greater than or equal to 126 mg/dL) that had gone undiagnosed (less than 0.5%), said Ms. Wallace and her associates.
Considering all hyperglycemia (undiagnosed diabetes or prediabetes) in the NHANES youth population, the sensitivity and specificity of the ADA criteria for detecting A1c-defined hyperglycemia (greater than or equal to 5.7%) were 56% and 76%, respectively, and the sensitivity and specificity for detecting FBG-defined hyperglycemia (greater than or equal to 100 mg/dL) were 36% and 77%.
The prevalence of any hyperglycemia was higher in youth who met ADA screening criteria than in those who didn’t, but there were also “a substantial number of youth with hyperglycemia in the non–screening eligible population,” they wrote. “In fact, the absolute number of youth with elevated FPG was larger in the non–screening eligible population, and the majority (88.5%) of these youth were of normal weight.”
Across all youth (irrespective of screening eligibility), both FPG and A1c-defined hyperglycemia effectively identified children and adolescents who had a high burden of cardiometabolic risk (obesity, metabolic syndrome, and hypercholesterolemia). Using a confirmatory definition of elevations in both FPG and A1c “provided the highest discrimination for cardiometabolic risk,” Ms. Wallace and her associates said.
But in comparing the single tests, risk factor associations with hyperglycemia were consistently stronger with A1c-defined hyperglycemia (odds ratios of 2.6-4.1) than FBG-defined hyperglycemia (ORs of 1.5-3.0). A1c-defined hyperglycemia “identifies a smaller, but higher-risk, population than FPG-defined hyperglycemia,” they said.
In an accompanying commentary, Tamara S. Hannon, MD, MS, of the division of pediatric endocrinology and diabetology at Indiana University in Indianapolis, said that more effective algorithms to determine who should have laboratory testing “could be useful.” Still, “for youth with obesity and multiple risk factors for developing type 2 diabetes, the principal challenge is how to effectively prevent or delay this disease for them and future generations.”
Pediatricians, she said, should screen for prediabetes and type 2 diabetes “according to professional recommendations with simple clinical tests, such as A1c. Screening and education about prediabetes alone can lead to better rates of follow-up for obesity,” she noted (Pediatrics. August 2020. doi: 10.1542/peds.2020-010272).
Sheela N. Magge, MD, MSCE, who directs the division of pediatric endocrinology and diabetes at John Hopkins University, Baltimore, and was asked to comment on the study, similarly said that the findings should not discourage use of the ADA guidelines.
While the guidelines may not have optimal sensitivity and specificity, “neither HbA1c nor fasting glucose are perfect screening tools for prediabetes and likely give us different mechanistic information,” she said. (The ADA guidelines also allow the use of a 2-hour oral glucose tolerance test, but this is not often used by pediatricians, she noted.)
The measurements are “only tools used to identify children who have prediabetes and are therefore at increased risk for type 2 diabetes,” said Dr. Magge, the Lawson Wilkins Endowed Chair of Pediatric Endocrinology at the university. “These children then need to be managed and followed to try to prevent worsening glycemia.”
Both she and Dr. Hannon stressed that youth with type 2 diabetes have more rapidly progressive disease compared with adults.
Microvascular complications are seen even at diagnosis, Dr. Magge said, and “youth may face serious complications such as cardiovascular disease decades earlier than previous generations.”
Dr. Hannon also noted in her commentary that oral diabetes medications often fail in youth with type 2 diabetes, leading to insulin therapy early on.
The prevalence of youth-onset type 2 diabetes has increased because of rising rates of pediatric overweight and obesity, Dr. Magge emphasized. In her experience, the diabetes risk factors that guide the ADA’s screening approach “are so common in overweight and obese youth that they all have at least one.”
The NHANES data did not contain information on all the variables that make up the current diabetes screening criteria in youth; there was no explicit information on history of maternal gestational diabetes and family history of type 2 diabetes, for instance, or the presence of acanthosis nigricans or polycystic ovarian syndrome – conditions associated with insulin resistance. The investigators said it’s likely, therefore, that the study underestimated the number of U.S. youth who would be eligible for diabetes screening.
And, as Dr. Magge said, “it is difficult to determine which risk factors [in the ADA guidelines] were less predictive.”
The NHANES analysis covered 14,119 youth in the 1999-2016 NHANES surveys, which consisted of interviews and standardized physical exams, including laboratory tests, in home and at a mobile examination center. Analyses involving any fasting lab tests were limited to a random subsample of participants aged 12-19 years without diagnosed diabetes who were asked to fast the night before; 6,225 youth properly followed instructions and were included in this subsample.
The surveys are conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. The study authors and the editorial author indicated that they have no relevant financial disclosures or conflicts of interest. Dr. Magge also said she has no relevant disclosures.
SOURCE: Wallace AS et al. Pediatrics. August 2020. doi: 10.1542/peds.2020-0265.
FROM PEDIATRICS
How three cardiac procedures changed in the COVID era
When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.
They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.
A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.
Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
More on TAVR in Virginia
Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.
Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.
Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”
Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.
Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”
This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.
The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.
TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.
“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”
More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.
“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
PCI in New York
Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.
When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”
She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.
That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.
Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”
For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”
Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”
There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.
“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.
In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.
Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.
By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
AFib ablation in Kentucky
As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.
There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.
All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”
In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.
During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.
Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.
When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.
They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.
A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.
Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
More on TAVR in Virginia
Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.
Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.
Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”
Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.
Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”
This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.
The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.
TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.
“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”
More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.
“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
PCI in New York
Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.
When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”
She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.
That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.
Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”
For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”
Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”
There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.
“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.
In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.
Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.
By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
AFib ablation in Kentucky
As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.
There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.
All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”
In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.
During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.
Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.
When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.
They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.
A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.
Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
More on TAVR in Virginia
Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.
Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.
Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”
Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.
Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”
This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.
The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.
TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.
“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”
More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.
“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
PCI in New York
Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.
When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”
She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.
That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.
Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”
For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”
Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”
There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.
“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.
In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.
Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.
By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
AFib ablation in Kentucky
As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.
There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.
All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”
In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.
During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.
Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.
Marked improvements seen for women in dermatology since the 1970s
Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.
“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”
Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.
Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.
It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
Women’s impact on the specialty
Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.
It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”
Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.
Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.
While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.
Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).
After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.
“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.
“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.
“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”
Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”
In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).
And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.
“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”
Phoebe Rich, MD, who owns a small all-woman practice and a research center in Portland, Oregon, said that, in general, many women also communicate and practice in a way that facilitates holistic care. “These qualities aren’t exclusive to women, but women are very caring. We take time and are interested in [patients’] lives in general, not just their disease.”
Disparities in academia
Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).
The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)
Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).
This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.
“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.
Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”
Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.
From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”
And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”
Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”
Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”
In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.
The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).
Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).
And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”
It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”
Work-life balance
In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”
If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”
Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”
Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”
In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”
In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”
Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.
“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”
Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.
Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.
It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
Women’s impact on the specialty
Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.
It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”
Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.
Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.
While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.
Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).
After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.
“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.
“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.
“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”
Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”
In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).
And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.
“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”
Phoebe Rich, MD, who owns a small all-woman practice and a research center in Portland, Oregon, said that, in general, many women also communicate and practice in a way that facilitates holistic care. “These qualities aren’t exclusive to women, but women are very caring. We take time and are interested in [patients’] lives in general, not just their disease.”
Disparities in academia
Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).
The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)
Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).
This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.
“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.
Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”
Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.
From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”
And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”
Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”
Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”
In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.
The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).
Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).
And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”
It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”
Work-life balance
In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”
If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”
Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”
Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”
In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”
In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”
Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.
“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”
Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.
Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.
It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
Women’s impact on the specialty
Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.
It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”
Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.
Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.
While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.
Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).
After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.
“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.
“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.
“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”
Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”
In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).
And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.
“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”
Phoebe Rich, MD, who owns a small all-woman practice and a research center in Portland, Oregon, said that, in general, many women also communicate and practice in a way that facilitates holistic care. “These qualities aren’t exclusive to women, but women are very caring. We take time and are interested in [patients’] lives in general, not just their disease.”
Disparities in academia
Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).
The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)
Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).
This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.
“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.
Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”
Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.
From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”
And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”
Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”
Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”
In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.
The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).
Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).
And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”
It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”
Work-life balance
In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”
If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”
Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”
Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”
In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”
In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”
COVID-19 drives nursing homes to overhaul infection control efforts
The toll that COVID-19 has taken on nursing homes and their postacute and long-term care residents has a multilayered backstory involving underresourced organizational structures, inherent susceptibilities, minimally trained infection prevention staff, variable abilities to isolate and quarantine large numbers of patients and residents, and a lack of governmental support.
“Nursing homes have been trying their best to combat this pandemic using the best infection control procedures they have, but blindfolded and with their hands tied behind their backs,” said Joseph G. Ouslander, MD, professor of geriatric medicine at Florida Atlantic University, Boca Raton, which has teaching affiliations with three senior communities.
Nursing home leaders are debating how to best use testing to guide transmission-based precautions and isolation strategies and how to keep residents safe while allowing some socialization after months of conflicting guidance from public health officials (on testing and on sites of care for patients discharged from the hospital, for instance), with a lack of adequate personal protective equipment (PPE) and testing supplies, and with nursing home resident deaths estimated to account for at least one-quarter of the total COVID-19–related mortality in the United States.
“COVID is not going away [over the next couple of years],” said Michael Wasserman, MD, medical director of the Eisenberg Village at the Los Angeles Jewish Home and president of the California Association of Long-Term Care Medicine.
Dr. Wasserman and other experts in both long-term care and infectious disease said in interviews that, through the rest of the pandemic and beyond, nursing homes need the following:
- Full-time, well-trained “infection preventionists” – infection prevention managers, in essence – who can lead improvements in emergency preparedness and infection prevention and control (IPC)
- Medical directors who are well qualified and engaged
- A survey/inspection process that is educational and not solely punitive
- More resources and attention to structural reform
“If this pandemic doesn’t create significant change in the nursing home industry, nothing ever will,” Dr. Wasserman said.
Prepandemic experience
When Ghinwa Dumyati, MD, began working with nursing homes in early March to prevent and contain COVID-19 outbreaks, her focus was on PPE.
Nursing home staff were intimately familiar with standard precautions, and many had used contact precautions to prevent transmission of infections like Clostridioides difficile and Candida auris, as well as droplet precautions for influenza. With the threat of COVID-19, nursing homes “had a brand-new requirement to do both contact and droplet precautions – with a new need for eye protection – and in some situations, respiratory precautions with N95 masks,” said Dr. Dumyati, professor of medicine and director of communicable disease surveillance and prevention at the University of Rochester (N.Y.) Medical Center. “And on top of that, [staff] had to learn to conserve and reuse PPE.”
Staff had not been fit-tested for use of N95 respirators, she noted. “The only time an N95 was used in the nursing home prior to COVID-19,” she said, “was for a suspected tuberculosis patient [before hospital admission].”
Similarly, nursing homes had experience in quarantining units to prevent transmission of illnesses like influenza or norovirus – keeping residents in their rooms with no visitations or social activity, for instance – but never did they have to arrange “massive movements of residents to completely new units or parts of a unit,” said Dr. Dumyati, who also has led hospital and nursing home collaborative programs in Rochester to beat back C. difficile, and is now helping to formulate COVID-19 recommendations and guidance for members of AMDA – The Society for Post-Acute and Long-Term Care.
As the SARS-CoV-2 virus began its spread through the United States, efforts to strengthen IPC programs in nursing homes in Rochester and elsewhere had been focused largely on multidrug resistant organisms (MDROs) and antibiotic stewardship – not on pandemic preparedness.
Reducing antibiotic use had become a national priority, and a 2016 rule by the Centers for Medicare & Medicaid Services required nursing homes to develop, over a 3-year period, an IPC program that included an antibiotic stewardship component and employment of a trained infection preventionist on at least a half-time basis. Emergency preparedness (e.g., having alternate energy sources for a facility) was also included in the rule, but it was only in 2019 when CMS updated its “Requirements for Participation” rule to stipulate that emergency preparedness include planning for “emerging infectious diseases.”
“The 2016 regulations came about because infections were so problematic in nursing homes,” especially urinary tract infections, C. difficile, and drug-resistant infections, said Patricia Stone, PhD, RN, of the Center for Health Policy at the Columbia University School of Nursing, New York, who has published widely on infection prevention and control in nursing homes.
An analysis of IPC practices in 2014 and in 2018 suggests that the IPC-focused rules were helping, mainly with antibiotic stewardship programs but also with respect to some of the practices aimed at outbreak control, such as having policies in place for grouping infected residents together, instructing infected staff to stay home, and quarantining units on which outbreaks occur, Dr. Stone said. Policies for confining residents to rooms were reported by approximately 74% of nursing homes in 2014, and by approximately 87% in 2018, for instance. Overall, nursing homes were “getting better policies in place,” she said. The analysis compared data from two cross-sectional surveys of nursing homes conducted in 2014 and 2018 (945 and 888 facilities, respectively).
Nursing homes “have a long way to go,” however, with respect to the training of infection preventionists, Dr. Stone said. In 2014, her analysis shows, almost 65% of infection preventionists had no specific infection-control training and less than 3% were Certified in Infection Control (CIC) – a credential awarded by the Certification Board of Infection Control & Epidemiology. Of the 35% who had some form of official training, most completed state or local training courses.
The numbers improved slightly in 2018, with 7% of nursing homes reporting their infection preventionists had the highest-level certification, and 44% reporting that their infection preventionists had no specific infection-control training. Research has shown that infection-control training of any kind has a “strong effect” on IPC-related outcomes. While not demonstrated in research thus far, it seems plausible that “facilities with certified [infection preventionists] will have better processes in place,” said Dr. Stone, whose research has documented the need for more monitoring of staff compliance with hand-washing and other IPC procedures.
Infection preventionists in nursing homes typically have been directors of nursing or assistant directors of nursing who fold IPC responsibilities into a multitude of other responsibilities. Before the 2016 rules, some smaller facilities hired off-site consultants to do the job.
CMS upped the ante after several months of COVID-19, recommending in mid-May that nursing homes assign at least one individual with training in infection control “to provide on-site management of the IPC program.” The infection preventionists should be a “full-time role” in facilities that have more than 100 residents, the CMS guidance said. (Prior to the pandemic, CMS issued proposed regulations in 2019 that would modify the time an infection preventionist must devote to a facility from “part time” to “sufficient time.”)
However, neither the 2016 rule nor the most recent guidance on infection preventionists define the length or content of training.
Swati Gaur, MD, chair of the Infection Advisory Committee of AMDA and a certified medical director of two skilled nursing facilities in Gainesville, Ga., said that the pandemic “has really started to crystallize some of the limitations of having a very vague role, not just in terms of what an [infection preventionists] does [in the nursing home] but also the training,”
Fortunately, Dr. Gaur said, when SARS-CoV-2 struck, she had just transitioned her facilities’ designated infection preventionist to work full-time on the role. She had worked closely with her infection preventionist on IPC issues but wishes she had arranged for more rigorous independent training. “The role of the [infection preventionist] is huge and complicated,” now involving employee health, contract tracing, cohorting, isolation, and compliance with precautions and use of PPE, in addition to surveillance, data reporting, and communication with public health officials, she said.
“Facilities are finding out now that [the infection preventionist] cannot be an afterthought. And it won’t end with COVID. We have other respiratory illnesses like flu and other viruses that we struggle with all the time,” said Dr. Gaur, who is working alongside Dr. Dumyati and two other long-term care experts on AMDA’s COVID-19 guidance. The nursing homes that Dr. Gaur directs are part of the Northeast Georgia Health Care System and together include 271 beds.
Moving forward
IPC practices often collide with facilities’ role as a home, especially to those receiving long-term care. “We always have to measure what we do [to prevent and control infections] against patient autonomy and residents’ rights,” said Dr. Gaur. “We have struggled with these issues, prior to the pandemic. If patients are positive for multidrug resistant organisms [for instance], how long can they be isolated in their own rooms? You can’t for days and months put someone in a single room and create isolation. That’s where the science of infection prevention can collide with residents’ rights.”
Over the years, the Centers for Disease Control and Prevention has acknowledged this discordance, leaving it to facilities to decide, for instance, whether to actively screen for colonization with MDROs. In 2019, to help nursing homes prevent the transmission of MDROs from residents who are colonized but not actively infected, the CDC introduced new “enhanced barrier precautions” that require the use of gowns and gloves for specific resident activities identified as having a high risk of MDRO transmission. The new category of precautions is less restrictive than traditional contact precautions, which keep residents in their rooms.
Infection control in nursing homes “isn’t where it needs to be ... but we’re always going to have in nursing homes a situation where there’s a high potential for rapid transmission of infectious disease,” said Christopher Crnich, MD, PhD, an infectious disease specialist at the University of Wisconsin–Madison who chairs the long-term care special interest group of the Society of Healthcare Epidemiology of America and has offered COVID-19 advice to his state’s department of public health.
“Anytime you have a congregative community, particularly one that involves susceptible hosts, there will be an intrinsically susceptible environment ... I’m a bit disturbed by the emphasis on saying, ‘This nursing home had a COVID-19 outbreak, therefore this nursing home did something wrong,’ ” Dr. Crnich said.
“How we mitigate the size of the outbreaks is where we need to focus our attention,” he said. The goal with SARS-CoV-2, he said, is to recognize its introduction “as rapidly as possible” and stop its spread through empiric symptom- and exposure-based isolation, multiple waves of targeted testing, widespread use of contact and droplet precautions, and isolating staff as necessary.
As awareness grew this year among long-term care leaders that relying too heavily on symptom-based strategies may not be effective to prevent introduction and transmission of SARS-CoV-2, a study published in April in the New England Journal of Medicine cemented the need for a testing strategy not limited to symptomatic individuals.
The study documented that more than half of residents in a nursing home who had positive polymerase chain reaction (PCR) test results were asymptomatic at the time of testing, and that most went on to develop symptoms. The study was conducted after one case of COVID-19 had been identified.
Some states issued calls this spring for “universal testing” of all nursing home patients and staff, and the CMS recommendations issued to state and local officials in mid-May for phased nursing home “reopening” call for baseline testing of all residents and staff, followed by retesting all residents weekly until all residents test negative and by retesting all staff continuing every week.
However, the experts contacted for this story said that, without a highly accurate and accessible point-of-care test (and even with one, considering the virus’ incubation period), a universal approach that includes all nursing home residents may have more limited value than is being touted. In many scenarios, they said, it is most meaningful to focus still-limited testing supplies on the staff, many of whom work at more than one facility and are believed to be primary vectors of SARS-CoV-2.
Dr. Ouslander, Dr. Wasserman and other long-term care leaders have been discussing testing at length, trying to reach consensus on best policies. “I don’t think there’s any uniform approach or uniform agreement,” said Dr. Ouslander. “For me, under ideal circumstances what needs to be done to protect older people in nursing homes is to get access to as many accurate viral tests as possible and test staff at least once a week or every 10 days.”
In some facilities, there may be an unspoken barrier to the frequent testing of staff: Fear that staff who test positive will need to be quarantined, with no one to take their place on the front line. Dr. Ouslander said he knows of one county health department that has discouraged nursing homes from testing asymptomatic staff. “It’s insane and truly shocking,” he said.
At the University of Rochester Medical Center, Dr. Dumyati said, staffing agencies are running short of nurse aide substitutes, and staffing issues have become the “biggest challenge” facing a regional multidisciplinary group of medical directors, hospital leaders, and health department officials who are working to troubleshoot COVID-19 issues. “Some of our nursing homes have ended up sending some of their residents to other nursing homes or to the hospital [because of the loss of staff],” she said.
Currently in the state of New York, she noted, COVID-19 patients may not be discharged to nursing homes until they test negative for the virus through PCR testing. “And some people don’t clear by PCR for 4-6 weeks.”
The barriers
Staffing shortages – real in some locales, and anticipated in others as economic reopening grows – are reflective of underlying structural and financial factors that work against optimal IPC, experts said. It’s not uncommon for certified nurse assistants (CNAs) to be assigned to 10-15 residents. And according to AMDA, 30%-46% of CNAs are reported to receive some form of public assistance. Low wages force many CNAs to work other jobs, including shifts at other nursing homes.
Turnover of nursing home leadership also creates problems. Dr. Crnich calls it “one of the biggest barriers” to effective IPC in nursing homes. “Facilities can tolerate some turnover in their front line staff,” he said, “as long as their leadership structure remains relatively stable.” Dr. Stone and her coinvestigators have documented at least yearly turnover in top positions: They found that, in 2018, approximately one-quarter of facilities reported employing three or more infection preventionists, three or more administrators, and three or more directors of nursing during the prior 3 years.
Medical directors, moreover, are not uniformly qualified, engaged with their facilities, or supported by nursing home administrators. “It’s an open secret, I think, that a lot of facilities want a medical director who is a good referral source,” said Dr. Gaur. “A medical director needs to be completely engaged in [quality improvement and] infection control practices.”
Some nursing home chains, she noted, “have realized the value of the medical director, and have changed the way they’re paying them. They’re actually holding them accountable [for quality and outcomes].”
Medical directors such as Dr. Wasserman, who previously oversaw a 74-facility nursing home chain in California as chief medical officer and then chief executive officer and has worked on nursing home quality improvement processes for his state, said there is much that can be done clinically to prevent the spread of infections, such as more frequent use of telemedicine, more attention to “deprescribing” unnecessary medications (which reduces the number of medication passes and, thus, the number of “transmission opportunities”), and the use of continuous remote monitoring. He has been trying to secure Bluetooth-enabled pulse oximetry and temperature monitoring for the Los Angeles Jewish Home and other facilities.
Dr. Wasserman and other long-term care leaders believe that a more educational inspection process would also lead to improvements in IPC. “The punitive nature of the survey process is morally deflating to frontline staff [and] penalties take money away from operations,” Dr. Wasserman said. “It’s not a productive approach to quality improvement.”
Dr. Stone agreed. Infection control is now the primary focus of CMS’s inspection process, and she said that increased regulatory scrutiny of IPC beyond COVID-19 is a “good thing.” Her research has shown that most deficiencies identified by inspectors are infection control deficiencies, and that in 2014 and 2018, approximately one-third of nursing homes had infection control citations. (CMS recently increased penalties and fines for identified deficiencies.)
“But my hope would be that the survey process would be more educational [as it is for hospitals],” she said. “We need to be supporting nursing homes to do a better job.”
A silver lining of the COVID-19 pandemic, as Dr. Stone sees it, is that nursing homes may be more engaged with data reporting and infection surveillance going forward. Nursing homes are now required to report their COVID-19 cases to the CDC through its hospital-dominant National Healthcare Safety Network, and the CDC has made technical changes that now make it “easier [than it was in the past] for nursing homes to join and participate,” she said. “Now that all nursing homes are engaged, will they be engaged post-COVID, too? I hope so. Surveillance [of infections] is a first step toward better outcomes.”
For now, said Dr. Crnich, the intensive prevention and mitigation efforts that are being required of nursing homes to minimize COVID-19’s impact is “a big deal and will tax the resources of most nursing homes and exceed the resources of many” without outside support, Dr. Crnich said. “This has been the most illuminating part of all this, and will probably require us to reconsider how we’re resourcing our nursing homes moving forward into the future.”
The toll that COVID-19 has taken on nursing homes and their postacute and long-term care residents has a multilayered backstory involving underresourced organizational structures, inherent susceptibilities, minimally trained infection prevention staff, variable abilities to isolate and quarantine large numbers of patients and residents, and a lack of governmental support.
“Nursing homes have been trying their best to combat this pandemic using the best infection control procedures they have, but blindfolded and with their hands tied behind their backs,” said Joseph G. Ouslander, MD, professor of geriatric medicine at Florida Atlantic University, Boca Raton, which has teaching affiliations with three senior communities.
Nursing home leaders are debating how to best use testing to guide transmission-based precautions and isolation strategies and how to keep residents safe while allowing some socialization after months of conflicting guidance from public health officials (on testing and on sites of care for patients discharged from the hospital, for instance), with a lack of adequate personal protective equipment (PPE) and testing supplies, and with nursing home resident deaths estimated to account for at least one-quarter of the total COVID-19–related mortality in the United States.
“COVID is not going away [over the next couple of years],” said Michael Wasserman, MD, medical director of the Eisenberg Village at the Los Angeles Jewish Home and president of the California Association of Long-Term Care Medicine.
Dr. Wasserman and other experts in both long-term care and infectious disease said in interviews that, through the rest of the pandemic and beyond, nursing homes need the following:
- Full-time, well-trained “infection preventionists” – infection prevention managers, in essence – who can lead improvements in emergency preparedness and infection prevention and control (IPC)
- Medical directors who are well qualified and engaged
- A survey/inspection process that is educational and not solely punitive
- More resources and attention to structural reform
“If this pandemic doesn’t create significant change in the nursing home industry, nothing ever will,” Dr. Wasserman said.
Prepandemic experience
When Ghinwa Dumyati, MD, began working with nursing homes in early March to prevent and contain COVID-19 outbreaks, her focus was on PPE.
Nursing home staff were intimately familiar with standard precautions, and many had used contact precautions to prevent transmission of infections like Clostridioides difficile and Candida auris, as well as droplet precautions for influenza. With the threat of COVID-19, nursing homes “had a brand-new requirement to do both contact and droplet precautions – with a new need for eye protection – and in some situations, respiratory precautions with N95 masks,” said Dr. Dumyati, professor of medicine and director of communicable disease surveillance and prevention at the University of Rochester (N.Y.) Medical Center. “And on top of that, [staff] had to learn to conserve and reuse PPE.”
Staff had not been fit-tested for use of N95 respirators, she noted. “The only time an N95 was used in the nursing home prior to COVID-19,” she said, “was for a suspected tuberculosis patient [before hospital admission].”
Similarly, nursing homes had experience in quarantining units to prevent transmission of illnesses like influenza or norovirus – keeping residents in their rooms with no visitations or social activity, for instance – but never did they have to arrange “massive movements of residents to completely new units or parts of a unit,” said Dr. Dumyati, who also has led hospital and nursing home collaborative programs in Rochester to beat back C. difficile, and is now helping to formulate COVID-19 recommendations and guidance for members of AMDA – The Society for Post-Acute and Long-Term Care.
As the SARS-CoV-2 virus began its spread through the United States, efforts to strengthen IPC programs in nursing homes in Rochester and elsewhere had been focused largely on multidrug resistant organisms (MDROs) and antibiotic stewardship – not on pandemic preparedness.
Reducing antibiotic use had become a national priority, and a 2016 rule by the Centers for Medicare & Medicaid Services required nursing homes to develop, over a 3-year period, an IPC program that included an antibiotic stewardship component and employment of a trained infection preventionist on at least a half-time basis. Emergency preparedness (e.g., having alternate energy sources for a facility) was also included in the rule, but it was only in 2019 when CMS updated its “Requirements for Participation” rule to stipulate that emergency preparedness include planning for “emerging infectious diseases.”
“The 2016 regulations came about because infections were so problematic in nursing homes,” especially urinary tract infections, C. difficile, and drug-resistant infections, said Patricia Stone, PhD, RN, of the Center for Health Policy at the Columbia University School of Nursing, New York, who has published widely on infection prevention and control in nursing homes.
An analysis of IPC practices in 2014 and in 2018 suggests that the IPC-focused rules were helping, mainly with antibiotic stewardship programs but also with respect to some of the practices aimed at outbreak control, such as having policies in place for grouping infected residents together, instructing infected staff to stay home, and quarantining units on which outbreaks occur, Dr. Stone said. Policies for confining residents to rooms were reported by approximately 74% of nursing homes in 2014, and by approximately 87% in 2018, for instance. Overall, nursing homes were “getting better policies in place,” she said. The analysis compared data from two cross-sectional surveys of nursing homes conducted in 2014 and 2018 (945 and 888 facilities, respectively).
Nursing homes “have a long way to go,” however, with respect to the training of infection preventionists, Dr. Stone said. In 2014, her analysis shows, almost 65% of infection preventionists had no specific infection-control training and less than 3% were Certified in Infection Control (CIC) – a credential awarded by the Certification Board of Infection Control & Epidemiology. Of the 35% who had some form of official training, most completed state or local training courses.
The numbers improved slightly in 2018, with 7% of nursing homes reporting their infection preventionists had the highest-level certification, and 44% reporting that their infection preventionists had no specific infection-control training. Research has shown that infection-control training of any kind has a “strong effect” on IPC-related outcomes. While not demonstrated in research thus far, it seems plausible that “facilities with certified [infection preventionists] will have better processes in place,” said Dr. Stone, whose research has documented the need for more monitoring of staff compliance with hand-washing and other IPC procedures.
Infection preventionists in nursing homes typically have been directors of nursing or assistant directors of nursing who fold IPC responsibilities into a multitude of other responsibilities. Before the 2016 rules, some smaller facilities hired off-site consultants to do the job.
CMS upped the ante after several months of COVID-19, recommending in mid-May that nursing homes assign at least one individual with training in infection control “to provide on-site management of the IPC program.” The infection preventionists should be a “full-time role” in facilities that have more than 100 residents, the CMS guidance said. (Prior to the pandemic, CMS issued proposed regulations in 2019 that would modify the time an infection preventionist must devote to a facility from “part time” to “sufficient time.”)
However, neither the 2016 rule nor the most recent guidance on infection preventionists define the length or content of training.
Swati Gaur, MD, chair of the Infection Advisory Committee of AMDA and a certified medical director of two skilled nursing facilities in Gainesville, Ga., said that the pandemic “has really started to crystallize some of the limitations of having a very vague role, not just in terms of what an [infection preventionists] does [in the nursing home] but also the training,”
Fortunately, Dr. Gaur said, when SARS-CoV-2 struck, she had just transitioned her facilities’ designated infection preventionist to work full-time on the role. She had worked closely with her infection preventionist on IPC issues but wishes she had arranged for more rigorous independent training. “The role of the [infection preventionist] is huge and complicated,” now involving employee health, contract tracing, cohorting, isolation, and compliance with precautions and use of PPE, in addition to surveillance, data reporting, and communication with public health officials, she said.
“Facilities are finding out now that [the infection preventionist] cannot be an afterthought. And it won’t end with COVID. We have other respiratory illnesses like flu and other viruses that we struggle with all the time,” said Dr. Gaur, who is working alongside Dr. Dumyati and two other long-term care experts on AMDA’s COVID-19 guidance. The nursing homes that Dr. Gaur directs are part of the Northeast Georgia Health Care System and together include 271 beds.
Moving forward
IPC practices often collide with facilities’ role as a home, especially to those receiving long-term care. “We always have to measure what we do [to prevent and control infections] against patient autonomy and residents’ rights,” said Dr. Gaur. “We have struggled with these issues, prior to the pandemic. If patients are positive for multidrug resistant organisms [for instance], how long can they be isolated in their own rooms? You can’t for days and months put someone in a single room and create isolation. That’s where the science of infection prevention can collide with residents’ rights.”
Over the years, the Centers for Disease Control and Prevention has acknowledged this discordance, leaving it to facilities to decide, for instance, whether to actively screen for colonization with MDROs. In 2019, to help nursing homes prevent the transmission of MDROs from residents who are colonized but not actively infected, the CDC introduced new “enhanced barrier precautions” that require the use of gowns and gloves for specific resident activities identified as having a high risk of MDRO transmission. The new category of precautions is less restrictive than traditional contact precautions, which keep residents in their rooms.
Infection control in nursing homes “isn’t where it needs to be ... but we’re always going to have in nursing homes a situation where there’s a high potential for rapid transmission of infectious disease,” said Christopher Crnich, MD, PhD, an infectious disease specialist at the University of Wisconsin–Madison who chairs the long-term care special interest group of the Society of Healthcare Epidemiology of America and has offered COVID-19 advice to his state’s department of public health.
“Anytime you have a congregative community, particularly one that involves susceptible hosts, there will be an intrinsically susceptible environment ... I’m a bit disturbed by the emphasis on saying, ‘This nursing home had a COVID-19 outbreak, therefore this nursing home did something wrong,’ ” Dr. Crnich said.
“How we mitigate the size of the outbreaks is where we need to focus our attention,” he said. The goal with SARS-CoV-2, he said, is to recognize its introduction “as rapidly as possible” and stop its spread through empiric symptom- and exposure-based isolation, multiple waves of targeted testing, widespread use of contact and droplet precautions, and isolating staff as necessary.
As awareness grew this year among long-term care leaders that relying too heavily on symptom-based strategies may not be effective to prevent introduction and transmission of SARS-CoV-2, a study published in April in the New England Journal of Medicine cemented the need for a testing strategy not limited to symptomatic individuals.
The study documented that more than half of residents in a nursing home who had positive polymerase chain reaction (PCR) test results were asymptomatic at the time of testing, and that most went on to develop symptoms. The study was conducted after one case of COVID-19 had been identified.
Some states issued calls this spring for “universal testing” of all nursing home patients and staff, and the CMS recommendations issued to state and local officials in mid-May for phased nursing home “reopening” call for baseline testing of all residents and staff, followed by retesting all residents weekly until all residents test negative and by retesting all staff continuing every week.
However, the experts contacted for this story said that, without a highly accurate and accessible point-of-care test (and even with one, considering the virus’ incubation period), a universal approach that includes all nursing home residents may have more limited value than is being touted. In many scenarios, they said, it is most meaningful to focus still-limited testing supplies on the staff, many of whom work at more than one facility and are believed to be primary vectors of SARS-CoV-2.
Dr. Ouslander, Dr. Wasserman and other long-term care leaders have been discussing testing at length, trying to reach consensus on best policies. “I don’t think there’s any uniform approach or uniform agreement,” said Dr. Ouslander. “For me, under ideal circumstances what needs to be done to protect older people in nursing homes is to get access to as many accurate viral tests as possible and test staff at least once a week or every 10 days.”
In some facilities, there may be an unspoken barrier to the frequent testing of staff: Fear that staff who test positive will need to be quarantined, with no one to take their place on the front line. Dr. Ouslander said he knows of one county health department that has discouraged nursing homes from testing asymptomatic staff. “It’s insane and truly shocking,” he said.
At the University of Rochester Medical Center, Dr. Dumyati said, staffing agencies are running short of nurse aide substitutes, and staffing issues have become the “biggest challenge” facing a regional multidisciplinary group of medical directors, hospital leaders, and health department officials who are working to troubleshoot COVID-19 issues. “Some of our nursing homes have ended up sending some of their residents to other nursing homes or to the hospital [because of the loss of staff],” she said.
Currently in the state of New York, she noted, COVID-19 patients may not be discharged to nursing homes until they test negative for the virus through PCR testing. “And some people don’t clear by PCR for 4-6 weeks.”
The barriers
Staffing shortages – real in some locales, and anticipated in others as economic reopening grows – are reflective of underlying structural and financial factors that work against optimal IPC, experts said. It’s not uncommon for certified nurse assistants (CNAs) to be assigned to 10-15 residents. And according to AMDA, 30%-46% of CNAs are reported to receive some form of public assistance. Low wages force many CNAs to work other jobs, including shifts at other nursing homes.
Turnover of nursing home leadership also creates problems. Dr. Crnich calls it “one of the biggest barriers” to effective IPC in nursing homes. “Facilities can tolerate some turnover in their front line staff,” he said, “as long as their leadership structure remains relatively stable.” Dr. Stone and her coinvestigators have documented at least yearly turnover in top positions: They found that, in 2018, approximately one-quarter of facilities reported employing three or more infection preventionists, three or more administrators, and three or more directors of nursing during the prior 3 years.
Medical directors, moreover, are not uniformly qualified, engaged with their facilities, or supported by nursing home administrators. “It’s an open secret, I think, that a lot of facilities want a medical director who is a good referral source,” said Dr. Gaur. “A medical director needs to be completely engaged in [quality improvement and] infection control practices.”
Some nursing home chains, she noted, “have realized the value of the medical director, and have changed the way they’re paying them. They’re actually holding them accountable [for quality and outcomes].”
Medical directors such as Dr. Wasserman, who previously oversaw a 74-facility nursing home chain in California as chief medical officer and then chief executive officer and has worked on nursing home quality improvement processes for his state, said there is much that can be done clinically to prevent the spread of infections, such as more frequent use of telemedicine, more attention to “deprescribing” unnecessary medications (which reduces the number of medication passes and, thus, the number of “transmission opportunities”), and the use of continuous remote monitoring. He has been trying to secure Bluetooth-enabled pulse oximetry and temperature monitoring for the Los Angeles Jewish Home and other facilities.
Dr. Wasserman and other long-term care leaders believe that a more educational inspection process would also lead to improvements in IPC. “The punitive nature of the survey process is morally deflating to frontline staff [and] penalties take money away from operations,” Dr. Wasserman said. “It’s not a productive approach to quality improvement.”
Dr. Stone agreed. Infection control is now the primary focus of CMS’s inspection process, and she said that increased regulatory scrutiny of IPC beyond COVID-19 is a “good thing.” Her research has shown that most deficiencies identified by inspectors are infection control deficiencies, and that in 2014 and 2018, approximately one-third of nursing homes had infection control citations. (CMS recently increased penalties and fines for identified deficiencies.)
“But my hope would be that the survey process would be more educational [as it is for hospitals],” she said. “We need to be supporting nursing homes to do a better job.”
A silver lining of the COVID-19 pandemic, as Dr. Stone sees it, is that nursing homes may be more engaged with data reporting and infection surveillance going forward. Nursing homes are now required to report their COVID-19 cases to the CDC through its hospital-dominant National Healthcare Safety Network, and the CDC has made technical changes that now make it “easier [than it was in the past] for nursing homes to join and participate,” she said. “Now that all nursing homes are engaged, will they be engaged post-COVID, too? I hope so. Surveillance [of infections] is a first step toward better outcomes.”
For now, said Dr. Crnich, the intensive prevention and mitigation efforts that are being required of nursing homes to minimize COVID-19’s impact is “a big deal and will tax the resources of most nursing homes and exceed the resources of many” without outside support, Dr. Crnich said. “This has been the most illuminating part of all this, and will probably require us to reconsider how we’re resourcing our nursing homes moving forward into the future.”
The toll that COVID-19 has taken on nursing homes and their postacute and long-term care residents has a multilayered backstory involving underresourced organizational structures, inherent susceptibilities, minimally trained infection prevention staff, variable abilities to isolate and quarantine large numbers of patients and residents, and a lack of governmental support.
“Nursing homes have been trying their best to combat this pandemic using the best infection control procedures they have, but blindfolded and with their hands tied behind their backs,” said Joseph G. Ouslander, MD, professor of geriatric medicine at Florida Atlantic University, Boca Raton, which has teaching affiliations with three senior communities.
Nursing home leaders are debating how to best use testing to guide transmission-based precautions and isolation strategies and how to keep residents safe while allowing some socialization after months of conflicting guidance from public health officials (on testing and on sites of care for patients discharged from the hospital, for instance), with a lack of adequate personal protective equipment (PPE) and testing supplies, and with nursing home resident deaths estimated to account for at least one-quarter of the total COVID-19–related mortality in the United States.
“COVID is not going away [over the next couple of years],” said Michael Wasserman, MD, medical director of the Eisenberg Village at the Los Angeles Jewish Home and president of the California Association of Long-Term Care Medicine.
Dr. Wasserman and other experts in both long-term care and infectious disease said in interviews that, through the rest of the pandemic and beyond, nursing homes need the following:
- Full-time, well-trained “infection preventionists” – infection prevention managers, in essence – who can lead improvements in emergency preparedness and infection prevention and control (IPC)
- Medical directors who are well qualified and engaged
- A survey/inspection process that is educational and not solely punitive
- More resources and attention to structural reform
“If this pandemic doesn’t create significant change in the nursing home industry, nothing ever will,” Dr. Wasserman said.
Prepandemic experience
When Ghinwa Dumyati, MD, began working with nursing homes in early March to prevent and contain COVID-19 outbreaks, her focus was on PPE.
Nursing home staff were intimately familiar with standard precautions, and many had used contact precautions to prevent transmission of infections like Clostridioides difficile and Candida auris, as well as droplet precautions for influenza. With the threat of COVID-19, nursing homes “had a brand-new requirement to do both contact and droplet precautions – with a new need for eye protection – and in some situations, respiratory precautions with N95 masks,” said Dr. Dumyati, professor of medicine and director of communicable disease surveillance and prevention at the University of Rochester (N.Y.) Medical Center. “And on top of that, [staff] had to learn to conserve and reuse PPE.”
Staff had not been fit-tested for use of N95 respirators, she noted. “The only time an N95 was used in the nursing home prior to COVID-19,” she said, “was for a suspected tuberculosis patient [before hospital admission].”
Similarly, nursing homes had experience in quarantining units to prevent transmission of illnesses like influenza or norovirus – keeping residents in their rooms with no visitations or social activity, for instance – but never did they have to arrange “massive movements of residents to completely new units or parts of a unit,” said Dr. Dumyati, who also has led hospital and nursing home collaborative programs in Rochester to beat back C. difficile, and is now helping to formulate COVID-19 recommendations and guidance for members of AMDA – The Society for Post-Acute and Long-Term Care.
As the SARS-CoV-2 virus began its spread through the United States, efforts to strengthen IPC programs in nursing homes in Rochester and elsewhere had been focused largely on multidrug resistant organisms (MDROs) and antibiotic stewardship – not on pandemic preparedness.
Reducing antibiotic use had become a national priority, and a 2016 rule by the Centers for Medicare & Medicaid Services required nursing homes to develop, over a 3-year period, an IPC program that included an antibiotic stewardship component and employment of a trained infection preventionist on at least a half-time basis. Emergency preparedness (e.g., having alternate energy sources for a facility) was also included in the rule, but it was only in 2019 when CMS updated its “Requirements for Participation” rule to stipulate that emergency preparedness include planning for “emerging infectious diseases.”
“The 2016 regulations came about because infections were so problematic in nursing homes,” especially urinary tract infections, C. difficile, and drug-resistant infections, said Patricia Stone, PhD, RN, of the Center for Health Policy at the Columbia University School of Nursing, New York, who has published widely on infection prevention and control in nursing homes.
An analysis of IPC practices in 2014 and in 2018 suggests that the IPC-focused rules were helping, mainly with antibiotic stewardship programs but also with respect to some of the practices aimed at outbreak control, such as having policies in place for grouping infected residents together, instructing infected staff to stay home, and quarantining units on which outbreaks occur, Dr. Stone said. Policies for confining residents to rooms were reported by approximately 74% of nursing homes in 2014, and by approximately 87% in 2018, for instance. Overall, nursing homes were “getting better policies in place,” she said. The analysis compared data from two cross-sectional surveys of nursing homes conducted in 2014 and 2018 (945 and 888 facilities, respectively).
Nursing homes “have a long way to go,” however, with respect to the training of infection preventionists, Dr. Stone said. In 2014, her analysis shows, almost 65% of infection preventionists had no specific infection-control training and less than 3% were Certified in Infection Control (CIC) – a credential awarded by the Certification Board of Infection Control & Epidemiology. Of the 35% who had some form of official training, most completed state or local training courses.
The numbers improved slightly in 2018, with 7% of nursing homes reporting their infection preventionists had the highest-level certification, and 44% reporting that their infection preventionists had no specific infection-control training. Research has shown that infection-control training of any kind has a “strong effect” on IPC-related outcomes. While not demonstrated in research thus far, it seems plausible that “facilities with certified [infection preventionists] will have better processes in place,” said Dr. Stone, whose research has documented the need for more monitoring of staff compliance with hand-washing and other IPC procedures.
Infection preventionists in nursing homes typically have been directors of nursing or assistant directors of nursing who fold IPC responsibilities into a multitude of other responsibilities. Before the 2016 rules, some smaller facilities hired off-site consultants to do the job.
CMS upped the ante after several months of COVID-19, recommending in mid-May that nursing homes assign at least one individual with training in infection control “to provide on-site management of the IPC program.” The infection preventionists should be a “full-time role” in facilities that have more than 100 residents, the CMS guidance said. (Prior to the pandemic, CMS issued proposed regulations in 2019 that would modify the time an infection preventionist must devote to a facility from “part time” to “sufficient time.”)
However, neither the 2016 rule nor the most recent guidance on infection preventionists define the length or content of training.
Swati Gaur, MD, chair of the Infection Advisory Committee of AMDA and a certified medical director of two skilled nursing facilities in Gainesville, Ga., said that the pandemic “has really started to crystallize some of the limitations of having a very vague role, not just in terms of what an [infection preventionists] does [in the nursing home] but also the training,”
Fortunately, Dr. Gaur said, when SARS-CoV-2 struck, she had just transitioned her facilities’ designated infection preventionist to work full-time on the role. She had worked closely with her infection preventionist on IPC issues but wishes she had arranged for more rigorous independent training. “The role of the [infection preventionist] is huge and complicated,” now involving employee health, contract tracing, cohorting, isolation, and compliance with precautions and use of PPE, in addition to surveillance, data reporting, and communication with public health officials, she said.
“Facilities are finding out now that [the infection preventionist] cannot be an afterthought. And it won’t end with COVID. We have other respiratory illnesses like flu and other viruses that we struggle with all the time,” said Dr. Gaur, who is working alongside Dr. Dumyati and two other long-term care experts on AMDA’s COVID-19 guidance. The nursing homes that Dr. Gaur directs are part of the Northeast Georgia Health Care System and together include 271 beds.
Moving forward
IPC practices often collide with facilities’ role as a home, especially to those receiving long-term care. “We always have to measure what we do [to prevent and control infections] against patient autonomy and residents’ rights,” said Dr. Gaur. “We have struggled with these issues, prior to the pandemic. If patients are positive for multidrug resistant organisms [for instance], how long can they be isolated in their own rooms? You can’t for days and months put someone in a single room and create isolation. That’s where the science of infection prevention can collide with residents’ rights.”
Over the years, the Centers for Disease Control and Prevention has acknowledged this discordance, leaving it to facilities to decide, for instance, whether to actively screen for colonization with MDROs. In 2019, to help nursing homes prevent the transmission of MDROs from residents who are colonized but not actively infected, the CDC introduced new “enhanced barrier precautions” that require the use of gowns and gloves for specific resident activities identified as having a high risk of MDRO transmission. The new category of precautions is less restrictive than traditional contact precautions, which keep residents in their rooms.
Infection control in nursing homes “isn’t where it needs to be ... but we’re always going to have in nursing homes a situation where there’s a high potential for rapid transmission of infectious disease,” said Christopher Crnich, MD, PhD, an infectious disease specialist at the University of Wisconsin–Madison who chairs the long-term care special interest group of the Society of Healthcare Epidemiology of America and has offered COVID-19 advice to his state’s department of public health.
“Anytime you have a congregative community, particularly one that involves susceptible hosts, there will be an intrinsically susceptible environment ... I’m a bit disturbed by the emphasis on saying, ‘This nursing home had a COVID-19 outbreak, therefore this nursing home did something wrong,’ ” Dr. Crnich said.
“How we mitigate the size of the outbreaks is where we need to focus our attention,” he said. The goal with SARS-CoV-2, he said, is to recognize its introduction “as rapidly as possible” and stop its spread through empiric symptom- and exposure-based isolation, multiple waves of targeted testing, widespread use of contact and droplet precautions, and isolating staff as necessary.
As awareness grew this year among long-term care leaders that relying too heavily on symptom-based strategies may not be effective to prevent introduction and transmission of SARS-CoV-2, a study published in April in the New England Journal of Medicine cemented the need for a testing strategy not limited to symptomatic individuals.
The study documented that more than half of residents in a nursing home who had positive polymerase chain reaction (PCR) test results were asymptomatic at the time of testing, and that most went on to develop symptoms. The study was conducted after one case of COVID-19 had been identified.
Some states issued calls this spring for “universal testing” of all nursing home patients and staff, and the CMS recommendations issued to state and local officials in mid-May for phased nursing home “reopening” call for baseline testing of all residents and staff, followed by retesting all residents weekly until all residents test negative and by retesting all staff continuing every week.
However, the experts contacted for this story said that, without a highly accurate and accessible point-of-care test (and even with one, considering the virus’ incubation period), a universal approach that includes all nursing home residents may have more limited value than is being touted. In many scenarios, they said, it is most meaningful to focus still-limited testing supplies on the staff, many of whom work at more than one facility and are believed to be primary vectors of SARS-CoV-2.
Dr. Ouslander, Dr. Wasserman and other long-term care leaders have been discussing testing at length, trying to reach consensus on best policies. “I don’t think there’s any uniform approach or uniform agreement,” said Dr. Ouslander. “For me, under ideal circumstances what needs to be done to protect older people in nursing homes is to get access to as many accurate viral tests as possible and test staff at least once a week or every 10 days.”
In some facilities, there may be an unspoken barrier to the frequent testing of staff: Fear that staff who test positive will need to be quarantined, with no one to take their place on the front line. Dr. Ouslander said he knows of one county health department that has discouraged nursing homes from testing asymptomatic staff. “It’s insane and truly shocking,” he said.
At the University of Rochester Medical Center, Dr. Dumyati said, staffing agencies are running short of nurse aide substitutes, and staffing issues have become the “biggest challenge” facing a regional multidisciplinary group of medical directors, hospital leaders, and health department officials who are working to troubleshoot COVID-19 issues. “Some of our nursing homes have ended up sending some of their residents to other nursing homes or to the hospital [because of the loss of staff],” she said.
Currently in the state of New York, she noted, COVID-19 patients may not be discharged to nursing homes until they test negative for the virus through PCR testing. “And some people don’t clear by PCR for 4-6 weeks.”
The barriers
Staffing shortages – real in some locales, and anticipated in others as economic reopening grows – are reflective of underlying structural and financial factors that work against optimal IPC, experts said. It’s not uncommon for certified nurse assistants (CNAs) to be assigned to 10-15 residents. And according to AMDA, 30%-46% of CNAs are reported to receive some form of public assistance. Low wages force many CNAs to work other jobs, including shifts at other nursing homes.
Turnover of nursing home leadership also creates problems. Dr. Crnich calls it “one of the biggest barriers” to effective IPC in nursing homes. “Facilities can tolerate some turnover in their front line staff,” he said, “as long as their leadership structure remains relatively stable.” Dr. Stone and her coinvestigators have documented at least yearly turnover in top positions: They found that, in 2018, approximately one-quarter of facilities reported employing three or more infection preventionists, three or more administrators, and three or more directors of nursing during the prior 3 years.
Medical directors, moreover, are not uniformly qualified, engaged with their facilities, or supported by nursing home administrators. “It’s an open secret, I think, that a lot of facilities want a medical director who is a good referral source,” said Dr. Gaur. “A medical director needs to be completely engaged in [quality improvement and] infection control practices.”
Some nursing home chains, she noted, “have realized the value of the medical director, and have changed the way they’re paying them. They’re actually holding them accountable [for quality and outcomes].”
Medical directors such as Dr. Wasserman, who previously oversaw a 74-facility nursing home chain in California as chief medical officer and then chief executive officer and has worked on nursing home quality improvement processes for his state, said there is much that can be done clinically to prevent the spread of infections, such as more frequent use of telemedicine, more attention to “deprescribing” unnecessary medications (which reduces the number of medication passes and, thus, the number of “transmission opportunities”), and the use of continuous remote monitoring. He has been trying to secure Bluetooth-enabled pulse oximetry and temperature monitoring for the Los Angeles Jewish Home and other facilities.
Dr. Wasserman and other long-term care leaders believe that a more educational inspection process would also lead to improvements in IPC. “The punitive nature of the survey process is morally deflating to frontline staff [and] penalties take money away from operations,” Dr. Wasserman said. “It’s not a productive approach to quality improvement.”
Dr. Stone agreed. Infection control is now the primary focus of CMS’s inspection process, and she said that increased regulatory scrutiny of IPC beyond COVID-19 is a “good thing.” Her research has shown that most deficiencies identified by inspectors are infection control deficiencies, and that in 2014 and 2018, approximately one-third of nursing homes had infection control citations. (CMS recently increased penalties and fines for identified deficiencies.)
“But my hope would be that the survey process would be more educational [as it is for hospitals],” she said. “We need to be supporting nursing homes to do a better job.”
A silver lining of the COVID-19 pandemic, as Dr. Stone sees it, is that nursing homes may be more engaged with data reporting and infection surveillance going forward. Nursing homes are now required to report their COVID-19 cases to the CDC through its hospital-dominant National Healthcare Safety Network, and the CDC has made technical changes that now make it “easier [than it was in the past] for nursing homes to join and participate,” she said. “Now that all nursing homes are engaged, will they be engaged post-COVID, too? I hope so. Surveillance [of infections] is a first step toward better outcomes.”
For now, said Dr. Crnich, the intensive prevention and mitigation efforts that are being required of nursing homes to minimize COVID-19’s impact is “a big deal and will tax the resources of most nursing homes and exceed the resources of many” without outside support, Dr. Crnich said. “This has been the most illuminating part of all this, and will probably require us to reconsider how we’re resourcing our nursing homes moving forward into the future.”
BMD preserved with investigational drug for uterine fibroid bleeding
Combination therapy with relugolix, an investigational oral gonadotropin-releasing hormone antagonist, estradiol, and norethindrone acetate effectively preserved bone mineral density (BMD) in two replicate phase 3 studies enrolling women with heavy menstrual bleeding associated with uterine fibroids.
The BMD findings, released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, build upon previously reported positive primary endpoint data from the LIBERTY 1 and LIBERTY 2 studies. ACOG canceled the meeting and released abstracts for press coverage.
The developer of the drug, Myovant Sciences, plans to submit a new drug application to the Food and Drug Administration for approval of the single-tablet combination therapy for women with uterine fibroids, according to Albert Liao, the company’s director of corporate communications.
The two multinational LIBERTY studies randomized women who had a monthly menstrual blood loss volume of at least 80 mL in two consecutive cycles (or 160 mL in one cycle) in a 1:1:1 ratio to one of three groups: relugolix combination therapy for 24 weeks (once-daily relugolix 40 mg plus estradiol 1.0 mg plus norethindrone acetate 0.5 mg); relugolix alone (40 mg once daily) for 12 weeks followed by relugolix combination therapy for 12 weeks; or placebo for 24 weeks.
In October 2019 at the American Society for Reproductive Medicine Scientific Congress, investigators reported that 73% of women receiving combination therapy in the LIBERTY 1 trial achieved a menstrual blood loss of less than 80 mL and a 50% or greater reduction from baseline over the last 35 days of treatment, compared with 19% in the placebo group. The mean percent reduction in menstrual blood loss from baseline at week 24 was 84% for combination therapy and 23% for placebo.
Earlier in 2019, Myovant Sciences announced that, in the LIBERTY 2 study, 71% of women receiving combination therapy met the primary endpoints, compared with 15% in the placebo group. The reduction in menstrual blood loss in this study’s combination therapy arm was also 84%, according to a company press release from June 2019.
Each of the two clinical trials enrolled upwards of 380 women.
The new abstract released for press coverage by ACOG and published in Obstetrics & Gynecology reports that women receiving relugolix combination therapy in the LIBERTY 1 and LIBERTY 2 studies had a mean change in lumbar spine BMD of –0.36% and –0.13%, respectively, from baseline to 24 weeks. Percent change in lumbar spine BMD in the delayed combination therapy groups (12 initial weeks of relugolix monotherapy) was –1.82% and –2.12%. In the placebo groups, the change was 0.05% and 0.32%.
Michael R. McClung, MD, who is the lead author of the abstract and was scheduled to present the findings at the ACOG meeting, said in an interview that the slight decreases in lumbar spine BMD with combination therapy were noted largely at week 12 and are “clinically insignificant in my opinion.” BMD by dual-energy x-ray absorptiometry was assessed at weeks 12 and 24.
“There was no further increase [after week 12] and [in some patients] there was even a return to baseline,” said Dr. McClung, of the Oregon Osteoporosis Center in Portland.
The safety and efficacy of longer-term treatment with relugolix combination therapy has been investigated thus far through an open-label extension study that brought the treatment period to 52 weeks. The 1-year data has been positive and will be presented or published soon, said Mr. Liao. In addition, a “second, 52-week randomized withdrawal study has been designed to provide 2-year safety and efficacy data … and to evaluate the need for maintenance therapy.”
It’s important, Dr. McClung said, “for clinicians to be confident that BMD loss is prevented or minimized with longer-term relugolix combination therapy since treatment for uterine fibroids is not a short-term proposition. Given the stability of BMD values between weeks 12 and 24 in the LIBERTY studies, I’d anticipate that we will see stable values with longer-term treatment.”
Dr. McClung disclosed that he has served as a consultant/advisory board member and speaker for Amgen and a consultant/advisory board member for Myovant. Several of his coauthors disclosed employment and ownerships interests in Myovant.
SOURCE: McClung MR et al. Obstet Gynecol. 2020 May. doi: 10.1097/01.AOG.0000662944.34860.b4.
Combination therapy with relugolix, an investigational oral gonadotropin-releasing hormone antagonist, estradiol, and norethindrone acetate effectively preserved bone mineral density (BMD) in two replicate phase 3 studies enrolling women with heavy menstrual bleeding associated with uterine fibroids.
The BMD findings, released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, build upon previously reported positive primary endpoint data from the LIBERTY 1 and LIBERTY 2 studies. ACOG canceled the meeting and released abstracts for press coverage.
The developer of the drug, Myovant Sciences, plans to submit a new drug application to the Food and Drug Administration for approval of the single-tablet combination therapy for women with uterine fibroids, according to Albert Liao, the company’s director of corporate communications.
The two multinational LIBERTY studies randomized women who had a monthly menstrual blood loss volume of at least 80 mL in two consecutive cycles (or 160 mL in one cycle) in a 1:1:1 ratio to one of three groups: relugolix combination therapy for 24 weeks (once-daily relugolix 40 mg plus estradiol 1.0 mg plus norethindrone acetate 0.5 mg); relugolix alone (40 mg once daily) for 12 weeks followed by relugolix combination therapy for 12 weeks; or placebo for 24 weeks.
In October 2019 at the American Society for Reproductive Medicine Scientific Congress, investigators reported that 73% of women receiving combination therapy in the LIBERTY 1 trial achieved a menstrual blood loss of less than 80 mL and a 50% or greater reduction from baseline over the last 35 days of treatment, compared with 19% in the placebo group. The mean percent reduction in menstrual blood loss from baseline at week 24 was 84% for combination therapy and 23% for placebo.
Earlier in 2019, Myovant Sciences announced that, in the LIBERTY 2 study, 71% of women receiving combination therapy met the primary endpoints, compared with 15% in the placebo group. The reduction in menstrual blood loss in this study’s combination therapy arm was also 84%, according to a company press release from June 2019.
Each of the two clinical trials enrolled upwards of 380 women.
The new abstract released for press coverage by ACOG and published in Obstetrics & Gynecology reports that women receiving relugolix combination therapy in the LIBERTY 1 and LIBERTY 2 studies had a mean change in lumbar spine BMD of –0.36% and –0.13%, respectively, from baseline to 24 weeks. Percent change in lumbar spine BMD in the delayed combination therapy groups (12 initial weeks of relugolix monotherapy) was –1.82% and –2.12%. In the placebo groups, the change was 0.05% and 0.32%.
Michael R. McClung, MD, who is the lead author of the abstract and was scheduled to present the findings at the ACOG meeting, said in an interview that the slight decreases in lumbar spine BMD with combination therapy were noted largely at week 12 and are “clinically insignificant in my opinion.” BMD by dual-energy x-ray absorptiometry was assessed at weeks 12 and 24.
“There was no further increase [after week 12] and [in some patients] there was even a return to baseline,” said Dr. McClung, of the Oregon Osteoporosis Center in Portland.
The safety and efficacy of longer-term treatment with relugolix combination therapy has been investigated thus far through an open-label extension study that brought the treatment period to 52 weeks. The 1-year data has been positive and will be presented or published soon, said Mr. Liao. In addition, a “second, 52-week randomized withdrawal study has been designed to provide 2-year safety and efficacy data … and to evaluate the need for maintenance therapy.”
It’s important, Dr. McClung said, “for clinicians to be confident that BMD loss is prevented or minimized with longer-term relugolix combination therapy since treatment for uterine fibroids is not a short-term proposition. Given the stability of BMD values between weeks 12 and 24 in the LIBERTY studies, I’d anticipate that we will see stable values with longer-term treatment.”
Dr. McClung disclosed that he has served as a consultant/advisory board member and speaker for Amgen and a consultant/advisory board member for Myovant. Several of his coauthors disclosed employment and ownerships interests in Myovant.
SOURCE: McClung MR et al. Obstet Gynecol. 2020 May. doi: 10.1097/01.AOG.0000662944.34860.b4.
Combination therapy with relugolix, an investigational oral gonadotropin-releasing hormone antagonist, estradiol, and norethindrone acetate effectively preserved bone mineral density (BMD) in two replicate phase 3 studies enrolling women with heavy menstrual bleeding associated with uterine fibroids.
The BMD findings, released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, build upon previously reported positive primary endpoint data from the LIBERTY 1 and LIBERTY 2 studies. ACOG canceled the meeting and released abstracts for press coverage.
The developer of the drug, Myovant Sciences, plans to submit a new drug application to the Food and Drug Administration for approval of the single-tablet combination therapy for women with uterine fibroids, according to Albert Liao, the company’s director of corporate communications.
The two multinational LIBERTY studies randomized women who had a monthly menstrual blood loss volume of at least 80 mL in two consecutive cycles (or 160 mL in one cycle) in a 1:1:1 ratio to one of three groups: relugolix combination therapy for 24 weeks (once-daily relugolix 40 mg plus estradiol 1.0 mg plus norethindrone acetate 0.5 mg); relugolix alone (40 mg once daily) for 12 weeks followed by relugolix combination therapy for 12 weeks; or placebo for 24 weeks.
In October 2019 at the American Society for Reproductive Medicine Scientific Congress, investigators reported that 73% of women receiving combination therapy in the LIBERTY 1 trial achieved a menstrual blood loss of less than 80 mL and a 50% or greater reduction from baseline over the last 35 days of treatment, compared with 19% in the placebo group. The mean percent reduction in menstrual blood loss from baseline at week 24 was 84% for combination therapy and 23% for placebo.
Earlier in 2019, Myovant Sciences announced that, in the LIBERTY 2 study, 71% of women receiving combination therapy met the primary endpoints, compared with 15% in the placebo group. The reduction in menstrual blood loss in this study’s combination therapy arm was also 84%, according to a company press release from June 2019.
Each of the two clinical trials enrolled upwards of 380 women.
The new abstract released for press coverage by ACOG and published in Obstetrics & Gynecology reports that women receiving relugolix combination therapy in the LIBERTY 1 and LIBERTY 2 studies had a mean change in lumbar spine BMD of –0.36% and –0.13%, respectively, from baseline to 24 weeks. Percent change in lumbar spine BMD in the delayed combination therapy groups (12 initial weeks of relugolix monotherapy) was –1.82% and –2.12%. In the placebo groups, the change was 0.05% and 0.32%.
Michael R. McClung, MD, who is the lead author of the abstract and was scheduled to present the findings at the ACOG meeting, said in an interview that the slight decreases in lumbar spine BMD with combination therapy were noted largely at week 12 and are “clinically insignificant in my opinion.” BMD by dual-energy x-ray absorptiometry was assessed at weeks 12 and 24.
“There was no further increase [after week 12] and [in some patients] there was even a return to baseline,” said Dr. McClung, of the Oregon Osteoporosis Center in Portland.
The safety and efficacy of longer-term treatment with relugolix combination therapy has been investigated thus far through an open-label extension study that brought the treatment period to 52 weeks. The 1-year data has been positive and will be presented or published soon, said Mr. Liao. In addition, a “second, 52-week randomized withdrawal study has been designed to provide 2-year safety and efficacy data … and to evaluate the need for maintenance therapy.”
It’s important, Dr. McClung said, “for clinicians to be confident that BMD loss is prevented or minimized with longer-term relugolix combination therapy since treatment for uterine fibroids is not a short-term proposition. Given the stability of BMD values between weeks 12 and 24 in the LIBERTY studies, I’d anticipate that we will see stable values with longer-term treatment.”
Dr. McClung disclosed that he has served as a consultant/advisory board member and speaker for Amgen and a consultant/advisory board member for Myovant. Several of his coauthors disclosed employment and ownerships interests in Myovant.
SOURCE: McClung MR et al. Obstet Gynecol. 2020 May. doi: 10.1097/01.AOG.0000662944.34860.b4.
FROM ACOG 2020
Testicular sperm may improve IVF outcomes in some cases
and rates of clinical pregnancy and live birth, a retrospective observational study has found.
The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
The study, which won the college’s Donald F. Richardson Memorial Prize Research Paper award, evaluated 112 nonazoospermic couples with an average of 2.3 failed in vitro fertilization (IVF) cycles (range of 1-8). The couples, patients at Shade Grove Fertility in Washington, underwent 157 total intracytoplasmic sperm injection (ICSI) cycles (133 using fresh testicular sperm and 24 using frozen/thawed sperm) and had a total of 101 embryo transfers.
Use of ICSI with testicular sperm compared with prior cycles using ejaculated sperm significantly improved blastocyst development (65% vs. 33%, P < .001), blastocyst conversion rates (67% vs. 35%, P < .001) and the number of embryos available for vitrification (1.6 vs. 0.7, P < .001). Fertilization rates were similar (70% vs. 58%). The clinical pregnancy and live birth rates in couples who used testicular sperm were 44% and 32%, respectively.
The findings suggest improved embryo development and pregnancy rates, and offer more evidence “that this might be something we can offer patients who’ve had multiple failures and no other reason as to why,” M. Blake Evans, DO, clinical fellow in reproductive endocrinology and infertility at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md., said in a interview. “It looks like there is promise, and we need more research to be conducted.”
The integration of the use of testicular sperm at Shady Grove, a private practice fertility center, and the newly completed analysis of outcomes, were driven by studies “showing that testicular sperm has a low DNA fragmentation index and suggesting that it [offers a] better chance of successful IVF outcomes in patients who have had prior failures,” he said.
Almost all of the men who had ICSC using testicular sperm – 105 of the 112 – had a sperm DNA fragmentation (SDF) assessment of their ejaculate sperm. The mean SDF was 32% and of these 105 men, 66 had an SDF greater than 25% (mean of 49%), a value considered abnormal. The outcomes for patients with elevated SDF did not differ significantly from the overall cohort, Dr. Evans and coinvestigators reported in their abstract.
Dr. Evans said that it’s too early to draw any conclusions about the utility of SDF testing, and that the investigators plan to start prospectively evaluating whether levels of sperm DNA damage as reflected in SDF testing correlate with IVF outcomes.
“Right now the evidence is so conflicting as to whether [SDF testing offers] information that all IVF patients or infertility patients should be receiving,” he said. “Is the reason that testicular sperm works better because there’s lower DNA fragmentation? We think so. … But now that we see [that it] appears the outcomes are better [using testicular sperm], we need to take it a step further and look prospectively at the impact of DNA fragmentation, comparing all the outcomes with normal and abnormal DNA [levels].”
Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview that while “there is increasing evidence – and rather clear evidence – that testicular sperm has less DNA damage,” there has been controversy over available outcomes data, most of which have come from small, retrospective studies. Dr. Trolice was not involved in this study presented at ACOG.
In the case of “very poor outcomes with use of ejaculated sperm and a high SDF index, there seems to be support for the use of testicular sperm on the next IVF cycle,” he said. “But there’s also evidence to support that there’s no significant difference in the outcomes of IUI [intrauterine insemination] or IVF based on the SDF index. So this [study] really took a tremendous leap of faith.”
Dr. Trolice said he looks forward to more research – ideally prospective, randomized studies of men with high SDF levels who proceed with assisted reproductive technologies using ejaculated or testicular sperm.
The research was supported by the division of intramural research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Evans did not report any relevant financial disclosures. One of his coinvestigators. Micah J. Hill, DO, disclosed having served on the advisory board of Ohana Biosciences. Dr. Trolice reported that he has no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
The abstract was first presented by coauthor Lt. Allison A. Eubanks, MD, of Walter Reed National Military Medical Center, at the ACOG Armed Forces District Annual District Meeting in September 2019.
and rates of clinical pregnancy and live birth, a retrospective observational study has found.
The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
The study, which won the college’s Donald F. Richardson Memorial Prize Research Paper award, evaluated 112 nonazoospermic couples with an average of 2.3 failed in vitro fertilization (IVF) cycles (range of 1-8). The couples, patients at Shade Grove Fertility in Washington, underwent 157 total intracytoplasmic sperm injection (ICSI) cycles (133 using fresh testicular sperm and 24 using frozen/thawed sperm) and had a total of 101 embryo transfers.
Use of ICSI with testicular sperm compared with prior cycles using ejaculated sperm significantly improved blastocyst development (65% vs. 33%, P < .001), blastocyst conversion rates (67% vs. 35%, P < .001) and the number of embryos available for vitrification (1.6 vs. 0.7, P < .001). Fertilization rates were similar (70% vs. 58%). The clinical pregnancy and live birth rates in couples who used testicular sperm were 44% and 32%, respectively.
The findings suggest improved embryo development and pregnancy rates, and offer more evidence “that this might be something we can offer patients who’ve had multiple failures and no other reason as to why,” M. Blake Evans, DO, clinical fellow in reproductive endocrinology and infertility at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md., said in a interview. “It looks like there is promise, and we need more research to be conducted.”
The integration of the use of testicular sperm at Shady Grove, a private practice fertility center, and the newly completed analysis of outcomes, were driven by studies “showing that testicular sperm has a low DNA fragmentation index and suggesting that it [offers a] better chance of successful IVF outcomes in patients who have had prior failures,” he said.
Almost all of the men who had ICSC using testicular sperm – 105 of the 112 – had a sperm DNA fragmentation (SDF) assessment of their ejaculate sperm. The mean SDF was 32% and of these 105 men, 66 had an SDF greater than 25% (mean of 49%), a value considered abnormal. The outcomes for patients with elevated SDF did not differ significantly from the overall cohort, Dr. Evans and coinvestigators reported in their abstract.
Dr. Evans said that it’s too early to draw any conclusions about the utility of SDF testing, and that the investigators plan to start prospectively evaluating whether levels of sperm DNA damage as reflected in SDF testing correlate with IVF outcomes.
“Right now the evidence is so conflicting as to whether [SDF testing offers] information that all IVF patients or infertility patients should be receiving,” he said. “Is the reason that testicular sperm works better because there’s lower DNA fragmentation? We think so. … But now that we see [that it] appears the outcomes are better [using testicular sperm], we need to take it a step further and look prospectively at the impact of DNA fragmentation, comparing all the outcomes with normal and abnormal DNA [levels].”
Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview that while “there is increasing evidence – and rather clear evidence – that testicular sperm has less DNA damage,” there has been controversy over available outcomes data, most of which have come from small, retrospective studies. Dr. Trolice was not involved in this study presented at ACOG.
In the case of “very poor outcomes with use of ejaculated sperm and a high SDF index, there seems to be support for the use of testicular sperm on the next IVF cycle,” he said. “But there’s also evidence to support that there’s no significant difference in the outcomes of IUI [intrauterine insemination] or IVF based on the SDF index. So this [study] really took a tremendous leap of faith.”
Dr. Trolice said he looks forward to more research – ideally prospective, randomized studies of men with high SDF levels who proceed with assisted reproductive technologies using ejaculated or testicular sperm.
The research was supported by the division of intramural research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Evans did not report any relevant financial disclosures. One of his coinvestigators. Micah J. Hill, DO, disclosed having served on the advisory board of Ohana Biosciences. Dr. Trolice reported that he has no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
The abstract was first presented by coauthor Lt. Allison A. Eubanks, MD, of Walter Reed National Military Medical Center, at the ACOG Armed Forces District Annual District Meeting in September 2019.
and rates of clinical pregnancy and live birth, a retrospective observational study has found.
The findings were released ahead of the study’s scheduled presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
The study, which won the college’s Donald F. Richardson Memorial Prize Research Paper award, evaluated 112 nonazoospermic couples with an average of 2.3 failed in vitro fertilization (IVF) cycles (range of 1-8). The couples, patients at Shade Grove Fertility in Washington, underwent 157 total intracytoplasmic sperm injection (ICSI) cycles (133 using fresh testicular sperm and 24 using frozen/thawed sperm) and had a total of 101 embryo transfers.
Use of ICSI with testicular sperm compared with prior cycles using ejaculated sperm significantly improved blastocyst development (65% vs. 33%, P < .001), blastocyst conversion rates (67% vs. 35%, P < .001) and the number of embryos available for vitrification (1.6 vs. 0.7, P < .001). Fertilization rates were similar (70% vs. 58%). The clinical pregnancy and live birth rates in couples who used testicular sperm were 44% and 32%, respectively.
The findings suggest improved embryo development and pregnancy rates, and offer more evidence “that this might be something we can offer patients who’ve had multiple failures and no other reason as to why,” M. Blake Evans, DO, clinical fellow in reproductive endocrinology and infertility at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md., said in a interview. “It looks like there is promise, and we need more research to be conducted.”
The integration of the use of testicular sperm at Shady Grove, a private practice fertility center, and the newly completed analysis of outcomes, were driven by studies “showing that testicular sperm has a low DNA fragmentation index and suggesting that it [offers a] better chance of successful IVF outcomes in patients who have had prior failures,” he said.
Almost all of the men who had ICSC using testicular sperm – 105 of the 112 – had a sperm DNA fragmentation (SDF) assessment of their ejaculate sperm. The mean SDF was 32% and of these 105 men, 66 had an SDF greater than 25% (mean of 49%), a value considered abnormal. The outcomes for patients with elevated SDF did not differ significantly from the overall cohort, Dr. Evans and coinvestigators reported in their abstract.
Dr. Evans said that it’s too early to draw any conclusions about the utility of SDF testing, and that the investigators plan to start prospectively evaluating whether levels of sperm DNA damage as reflected in SDF testing correlate with IVF outcomes.
“Right now the evidence is so conflicting as to whether [SDF testing offers] information that all IVF patients or infertility patients should be receiving,” he said. “Is the reason that testicular sperm works better because there’s lower DNA fragmentation? We think so. … But now that we see [that it] appears the outcomes are better [using testicular sperm], we need to take it a step further and look prospectively at the impact of DNA fragmentation, comparing all the outcomes with normal and abnormal DNA [levels].”
Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, said in an interview that while “there is increasing evidence – and rather clear evidence – that testicular sperm has less DNA damage,” there has been controversy over available outcomes data, most of which have come from small, retrospective studies. Dr. Trolice was not involved in this study presented at ACOG.
In the case of “very poor outcomes with use of ejaculated sperm and a high SDF index, there seems to be support for the use of testicular sperm on the next IVF cycle,” he said. “But there’s also evidence to support that there’s no significant difference in the outcomes of IUI [intrauterine insemination] or IVF based on the SDF index. So this [study] really took a tremendous leap of faith.”
Dr. Trolice said he looks forward to more research – ideally prospective, randomized studies of men with high SDF levels who proceed with assisted reproductive technologies using ejaculated or testicular sperm.
The research was supported by the division of intramural research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Evans did not report any relevant financial disclosures. One of his coinvestigators. Micah J. Hill, DO, disclosed having served on the advisory board of Ohana Biosciences. Dr. Trolice reported that he has no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
The abstract was first presented by coauthor Lt. Allison A. Eubanks, MD, of Walter Reed National Military Medical Center, at the ACOG Armed Forces District Annual District Meeting in September 2019.
FROM ACOG 2020
Vaginal cleansing at cesarean delivery works in practice
Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.
“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.
Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.
Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.
The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.
Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.
Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).
A subgroup analysis showed that Dr. Quist-Nelson said.
Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.
The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.
Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.
Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.
Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.
Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.
“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.
Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.
Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.
The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.
Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.
Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).
A subgroup analysis showed that Dr. Quist-Nelson said.
Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.
The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.
Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.
Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.
Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.
Vaginal cleansing before cesarean delivery was successfully implemented – and significantly decreased the rate of surgical site infections (SSI) – in a quality improvement study done at Thomas Jefferson University Hospital in Philadelphia.
“Our goal was not to prove that vaginal preparation [before cesarean section] works, because that’s already been shown in large randomized, controlled trials, but to show that we can implement it and that we can see the same results in real life,” lead investigator Johanna Quist-Nelson, MD, said in an interview.
Dr. Quist-Nelson, a third-year fellow at the hospital and the department of obstetrics and gynecology at Sidney Kimmel Medical College, Philadelphia, was scheduled to present the findings at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. ACOG canceled the meeting and released abstracts for press coverage.
Resident and staff physicians as well as nursing and operating room staff were educated/reminded through a multipronged intervention about the benefits of vaginal cleansing with a sponge stick preparation of 10% povidone-iodine solution (Betadine) – and later about the potential benefits of intravenous azithromycin – immediately before cesarean delivery for women in labor and women with ruptured membranes.
Dr. Quist-Nelson and coinvestigators compared three periods of time: 12 months preintervention, 14 months with vaginal cleansing promoted for infection prophylaxis, and 16 months of instructions for both vaginal cleansing and intravenous azithromycin. The three periods captured 1,033 patients. The researchers used control charts – a tool “often used in implementation science,” she said – to analyze monthly data and assess trends for SSI rates and for compliance.
The rate of SSI – as defined by the Centers for Disease Control and Prevention – decreased by 33%, they found, from 23% to 15%. The drop occurred mainly 4 months into the vaginal cleansing portion of the study and was sustained during the following 26 months. The addition of intravenous azithromycin education did not result in any further change in the SSI rate, Dr. Quist-Nelson and associates reported in the study – the abstract for which was published in Obstetrics & Gynecology. It won a third-place prize among the papers on current clinical and basic investigation.
Compliance with the vaginal cleansing protocol increased from 60% at the start of the vaginal cleansing phase to 85% 1 year later. Azithromycin compliance rose to 75% over the third phase of the intervention.
Vaginal cleansing has received attention at Thomas Jefferson for several years. In 2017, researchers there collaborated with investigators in Italy on a systemic review and meta-analysis which concluded that women who received vaginal cleansing before cesarean delivery – most commonly with 10% povidine-iodine – had a significantly lower incidence of endometritis (Obstet Gynecol. 2017 Sep;130[3]:527-38).
A subgroup analysis showed that Dr. Quist-Nelson said.
Azithromycin similarly was found to reduce the risk of postoperative infection in women undergoing nonelective cesarean deliveries in a randomized trial published in 2016 (N Engl J Med. 2016 Sep 29;375[13]:1231-41). While the new quality improvement study did not suggest any additional benefit to intravenous azithromycin, “we continue to offer it [at our hospital] because it has been shown [in prior research] to be beneficial and because our study wasn’t [designed] to show benefit,” Dr. Quist-Nelson said.
The quality improvement intervention included hands-on training on vaginal cleansing for resident physicians and e-mail reminders for physician staff, and daily reviews for 1 week on intravenous azithromycin for resident physicians and EMR “best practice advisory” reminders for physician staff. “We also wrote a protocol available online, and put reminders in our OR notes, as well as trained the nursing staff and OR staff,” she said.
Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview that SSI rates are “problematic [in obstetrics], not only because of morbidity but also potential cost because of rehospitalization.” The study shows that vaginal cleansing “is absolutely a good target for quality improvement,” she said. “It’s promising, and very exciting to see something like this have such a dramatic positive result.” Dr. Cansino, who is a member of the Ob.Gyn News editorial advisory board, was not involved in this study.
Thomas Jefferson Hospital has had relatively high SSI rates, Dr. Quist-Nelson noted.
Dr. Quist-Nelson and coinvestigators did not report any potential conflicts of interest. Dr. Cansino also did not report any potential conflicts of interest.
SOURCE: Quist-Nelson J et al. Obstet. Gynecol. 2020 May;135:1S. doi: 10.1097/01.AOG.0000662876.23603.13.
REPORTING FROM ACOG 2020
Dermatology therapies evolve as disease knowledge and investment grow
For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.
“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”
Much has changed. by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.
Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.
This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.
Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.
Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”
Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.
The new frontier of atopic dermatitis
The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”
As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.
But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”
Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.
“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.
Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”
Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.
“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”
Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.
“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”
Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.
“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”
Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.
JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”
Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.
In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
Spillover to other diseases
JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.
“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”
Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.
“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”
Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
Action on rare skin diseases
Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.
According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).
Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.
Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.
“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.
While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.
Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.
Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”
Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.
For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.
“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”
Much has changed. by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.
Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.
This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.
Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.
Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”
Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.
The new frontier of atopic dermatitis
The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”
As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.
But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”
Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.
“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.
Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”
Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.
“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”
Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.
“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”
Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.
“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”
Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.
JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”
Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.
In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
Spillover to other diseases
JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.
“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”
Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.
“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”
Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
Action on rare skin diseases
Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.
According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).
Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.
Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.
“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.
While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.
Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.
Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”
Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.
For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.
“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”
Much has changed. by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.
Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.
This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.
Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.
Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”
Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.
The new frontier of atopic dermatitis
The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”
As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.
But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”
Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.
“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.
Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”
Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.
“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”
Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.
“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”
Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.
“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”
Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.
JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”
Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.
In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
Spillover to other diseases
JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.
“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”
Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.
“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”
Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
Action on rare skin diseases
Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.
According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).
Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.
Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.
“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.
While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.
Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.
Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”
Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.
Resident experience with hysterectomy is on the decline
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
FROM OBSTETRICS & GYNECOLOGY
Gestational diabetes: Treatment controversy rages on
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
EXPERT ANALYSIS FROM DPSG-NA 2019