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azzed
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bullturds
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cocaine
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cocainees
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crackwhore
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cum
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cumsluted
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cunthunterer
cunthunteres
cunthuntering
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cunthunters
cunting
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cuntlicked
cuntlicker
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dagos
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damn
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damneder
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dickbag
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dickbags
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dickdippered
dickdipperer
dickdipperes
dickdippering
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dicker
dickes
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dickfaceed
dickfaceer
dickfacees
dickfaceing
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dickflippered
dickflipperer
dickflipperes
dickflippering
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dickheaded
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dickheadser
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dingleed
dingleer
dinglees
dingleing
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dipship
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dipshipes
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dizzyed
dizzyer
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dizzying
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dizzys
doggiestyleed
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dopeyer
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drunker
drunkes
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dumass
dumassed
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dumasses
dumassing
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dumasss
dumbass
dumbassed
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dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
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dyke
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dykeer
dykees
dykeing
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erotic
eroticed
eroticer
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erotics
extacy
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extacying
extacyly
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extasy
extasyed
extasyer
extasyes
extasying
extasyly
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facked
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faged
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fagged
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faggoted
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fagoted
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faiged
faiger
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faigts
fannybandit
fannybandited
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fannybandits
farted
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fartknockered
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fartly
farts
felch
felched
felcher
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fellateer
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fellateing
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fellatio
fellatioed
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feltched
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floozy
floozyed
floozyer
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foad
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freexes
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friggaer
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fuckined
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fuckinged
fuckinger
fuckinges
fuckinging
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fuckings
fuckining
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Ob.gyn. pay up slightly during pandemic, survey finds
Although 45% of ob.gyns. reported some decline in compensation during the pandemic, they earned more income in 2020 than they did in 2019, according to the 2021 Medscape Ob/Gyn Compensation Report.
The report, which surveyed nearly 18,000 physicians in more than 29 specialties, found that ob.gyns.’ income level was $312,000 in 2020, compared with $308,000 in 2019.
Despite the $4,000 increase, they still ranked near the bottom half in comparison with all other specialties. The lowest-paid specialties were public health & preventive medicine ($237,000), family medicine ($236,000), and pediatrics ($221,000), and the top earning specialties were plastic surgery ($526,000), orthopedics ($511,000), and cardiology ($459,000).
Optimistic about financial bounce back
Most ob.gyns. who experienced income loss cited job loss, reduction in hours, and lower patient volume because of the COVID-19 pandemic as reasons for their wage decline.
The specialty’s average incentive bonus, which is usually based on productivity and can be tied to patient satisfaction and clinical processes, was $48,000, and accounted for about 14% of total salary.
Of the ob.gyns. who reported financial losses during the pandemic, 41% expect their income to return to normal this year. However, 45% believe it will take 2-3 years to bounce back from the pandemic’s financial effect. About 11% believe they will never return to their pre–COVID-19 income.
Working similar hours, seeing fewer patients
The survey also found that ob.gyns. are back to working about the same number of hours they did prepandemic. Ob.gyns. currently work on average 54 hours per week, compared with the 56 hours per week they worked before the pandemic. However, they are only seeing 76 patients per week, compared with 81 patients per week before the pandemic.
Ob.gyns. reported spending 15.1 hours per week on medical-related work outside of patient visits, including paperwork, EHR documentation, administrative and managerial work, and clinical reading. The time required was slightly longer than last year (14.3 hours per week).
Similar to last year’s report, 55% of ob.gyns. said they are fairly compensated. Around 34% of them said the most rewarding part of their job is the relationships they have with their patients, followed by helping others (23%), and being good at what they do (22%). Only 11% said money was the most rewarding part of their job.
Challenges
The pandemic has brought many challenges for physicians, including financial difficulties and the potential to be exposed to SARS-CoV-2. However, when asked about the most challenging part of their job, only 4% of ob.gyns. said the danger or risk associated with treating patients with COVID-19 was the most challenging aspect of their job. By contrast, 21% of ob.gyns. said working long hours and having so many rules and regulations bog down their daily work.
Despite the pandemic-related challenges, 74% of ob.gyns. said they would choose medicine again and work in the same specialty.
A version of this article first appeared on Medscape.com.
Although 45% of ob.gyns. reported some decline in compensation during the pandemic, they earned more income in 2020 than they did in 2019, according to the 2021 Medscape Ob/Gyn Compensation Report.
The report, which surveyed nearly 18,000 physicians in more than 29 specialties, found that ob.gyns.’ income level was $312,000 in 2020, compared with $308,000 in 2019.
Despite the $4,000 increase, they still ranked near the bottom half in comparison with all other specialties. The lowest-paid specialties were public health & preventive medicine ($237,000), family medicine ($236,000), and pediatrics ($221,000), and the top earning specialties were plastic surgery ($526,000), orthopedics ($511,000), and cardiology ($459,000).
Optimistic about financial bounce back
Most ob.gyns. who experienced income loss cited job loss, reduction in hours, and lower patient volume because of the COVID-19 pandemic as reasons for their wage decline.
The specialty’s average incentive bonus, which is usually based on productivity and can be tied to patient satisfaction and clinical processes, was $48,000, and accounted for about 14% of total salary.
Of the ob.gyns. who reported financial losses during the pandemic, 41% expect their income to return to normal this year. However, 45% believe it will take 2-3 years to bounce back from the pandemic’s financial effect. About 11% believe they will never return to their pre–COVID-19 income.
Working similar hours, seeing fewer patients
The survey also found that ob.gyns. are back to working about the same number of hours they did prepandemic. Ob.gyns. currently work on average 54 hours per week, compared with the 56 hours per week they worked before the pandemic. However, they are only seeing 76 patients per week, compared with 81 patients per week before the pandemic.
Ob.gyns. reported spending 15.1 hours per week on medical-related work outside of patient visits, including paperwork, EHR documentation, administrative and managerial work, and clinical reading. The time required was slightly longer than last year (14.3 hours per week).
Similar to last year’s report, 55% of ob.gyns. said they are fairly compensated. Around 34% of them said the most rewarding part of their job is the relationships they have with their patients, followed by helping others (23%), and being good at what they do (22%). Only 11% said money was the most rewarding part of their job.
Challenges
The pandemic has brought many challenges for physicians, including financial difficulties and the potential to be exposed to SARS-CoV-2. However, when asked about the most challenging part of their job, only 4% of ob.gyns. said the danger or risk associated with treating patients with COVID-19 was the most challenging aspect of their job. By contrast, 21% of ob.gyns. said working long hours and having so many rules and regulations bog down their daily work.
Despite the pandemic-related challenges, 74% of ob.gyns. said they would choose medicine again and work in the same specialty.
A version of this article first appeared on Medscape.com.
Although 45% of ob.gyns. reported some decline in compensation during the pandemic, they earned more income in 2020 than they did in 2019, according to the 2021 Medscape Ob/Gyn Compensation Report.
The report, which surveyed nearly 18,000 physicians in more than 29 specialties, found that ob.gyns.’ income level was $312,000 in 2020, compared with $308,000 in 2019.
Despite the $4,000 increase, they still ranked near the bottom half in comparison with all other specialties. The lowest-paid specialties were public health & preventive medicine ($237,000), family medicine ($236,000), and pediatrics ($221,000), and the top earning specialties were plastic surgery ($526,000), orthopedics ($511,000), and cardiology ($459,000).
Optimistic about financial bounce back
Most ob.gyns. who experienced income loss cited job loss, reduction in hours, and lower patient volume because of the COVID-19 pandemic as reasons for their wage decline.
The specialty’s average incentive bonus, which is usually based on productivity and can be tied to patient satisfaction and clinical processes, was $48,000, and accounted for about 14% of total salary.
Of the ob.gyns. who reported financial losses during the pandemic, 41% expect their income to return to normal this year. However, 45% believe it will take 2-3 years to bounce back from the pandemic’s financial effect. About 11% believe they will never return to their pre–COVID-19 income.
Working similar hours, seeing fewer patients
The survey also found that ob.gyns. are back to working about the same number of hours they did prepandemic. Ob.gyns. currently work on average 54 hours per week, compared with the 56 hours per week they worked before the pandemic. However, they are only seeing 76 patients per week, compared with 81 patients per week before the pandemic.
Ob.gyns. reported spending 15.1 hours per week on medical-related work outside of patient visits, including paperwork, EHR documentation, administrative and managerial work, and clinical reading. The time required was slightly longer than last year (14.3 hours per week).
Similar to last year’s report, 55% of ob.gyns. said they are fairly compensated. Around 34% of them said the most rewarding part of their job is the relationships they have with their patients, followed by helping others (23%), and being good at what they do (22%). Only 11% said money was the most rewarding part of their job.
Challenges
The pandemic has brought many challenges for physicians, including financial difficulties and the potential to be exposed to SARS-CoV-2. However, when asked about the most challenging part of their job, only 4% of ob.gyns. said the danger or risk associated with treating patients with COVID-19 was the most challenging aspect of their job. By contrast, 21% of ob.gyns. said working long hours and having so many rules and regulations bog down their daily work.
Despite the pandemic-related challenges, 74% of ob.gyns. said they would choose medicine again and work in the same specialty.
A version of this article first appeared on Medscape.com.
Mother-to-infant COVID-19 transmission is unlikely
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
FROM PAS 2021
No survival dip with neoadjuvant letrozole-palbociclib in NeoPAL study
Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.
Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.
There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).
“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.
“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.
However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
Primary data already reported
The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.
Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.
Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2), followed by three 21-day cycles of docetaxel (100 mg/m2).
The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).
There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.
The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
Future studies needed
NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.
Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”
Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”
Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.
Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.
“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.
Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”
NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.
Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.
Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.
There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).
“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.
“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.
However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
Primary data already reported
The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.
Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.
Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2), followed by three 21-day cycles of docetaxel (100 mg/m2).
The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).
There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.
The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
Future studies needed
NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.
Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”
Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”
Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.
Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.
“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.
Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”
NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.
Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.
Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.
There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).
“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.
“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.
“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.
However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
Primary data already reported
The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.
Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.
Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2), followed by three 21-day cycles of docetaxel (100 mg/m2).
The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).
There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.
The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
Future studies needed
NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.
Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”
Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”
Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.
Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.
“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.
Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”
NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.
FROM ESMO BREAST CANCER 2021
New guidance for those fully vaccinated against COVID-19
As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19.
This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.
The new guidance indicates that quarantine after a known exposure is no longer necessary.
Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.
The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.1
Updated guidance for health care facilities
In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.2
There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.
Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.
Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.1,2
Pros and cons to new guidance
Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.
These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.
My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.
There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.
Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
How to continue exercising caution
With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.
I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.
There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.
Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.
2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.
As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19.
This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.
The new guidance indicates that quarantine after a known exposure is no longer necessary.
Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.
The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.1
Updated guidance for health care facilities
In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.2
There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.
Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.
Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.1,2
Pros and cons to new guidance
Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.
These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.
My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.
There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.
Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
How to continue exercising caution
With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.
I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.
There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.
Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.
2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.
As has been dominating the headlines, the Centers for Disease Control and Prevention recently released updated public health guidance for those who are fully vaccinated against COVID-19.
This new guidance applies to those who are fully vaccinated as indicated by 2 weeks after the second dose in a 2-dose series or 2 weeks after a single-dose vaccine. Those who meet these criteria no longer need to wear a mask or physically distance themselves from others in both indoor and outdoor settings. For those not fully vaccinated, masking and social distancing should continue to be practiced.
The new guidance indicates that quarantine after a known exposure is no longer necessary.
Unless required by local, state, or territorial health authorities, testing is no longer required following domestic travel for fully vaccinated individuals. A negative test is still required prior to boarding an international flight to the United States and testing 3-5 days after arrival is still recommended. Self-quarantine is no longer required after international travel for fully vaccinated individuals.
The new guidance recommends that individuals who are fully vaccinated not participate in routine screening programs when feasible. Finally, if an individual has tested positive for COVID-19, regardless of vaccination status, that person should isolate and not visit public or private settings for a minimum of ten days.1
Updated guidance for health care facilities
In addition to changes for the general public in all settings, the CDC updated guidance for health care facilities on April 27, 2021. These updated guidelines allow for communal dining and visitation for fully vaccinated patients and their visitors. The guidelines indicate that fully vaccinated health care personnel (HCP) do not require quarantine after exposure to patients who have tested positive for COVID-19 as long as the HCP remains asymptomatic. They should, however, continue to utilize personal protective equipment as previously recommended. HCPs are able to be in break and meeting rooms unmasked if all HCPs are vaccinated.2
There are some important caveats to these updated guidelines. They do not apply to those who have immunocompromising conditions, including those using immunosuppressant agents. They also do not apply to locations subject to federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.
Those who work or reside in correction or detention facilities and homeless shelters are also still required to test after known exposures. Masking is still required by all travelers on all forms of public transportation into and within the United States.
Most importantly, the guidelines apply only to those who are fully vaccinated. Finally, no vaccine is perfect. As such, anyone who experiences symptoms indicative of COVID-19, regardless of vaccination status, should obtain viral testing and isolate themselves from others.1,2
Pros and cons to new guidance
Both sets of updated guidelines are a great example of public health guidance that is changing as the evidence is gathered and changes. This guidance is also a welcome encouragement that the vaccines are effective at decreasing transmission of this virus that has upended our world.
These guidelines leave room for change as evidence is gathered on emerging novel variants. There are, however, a few remaining concerns.
My first concern is for those who are not yet able to be vaccinated, including children under the age of 12. For families with members who are not fully vaccinated, they may have first heard the headlines of “you do not have to mask” to then read the fine print that remains. When truly following these guidelines, many social situations in both the public and private setting should still include both masking and social distancing.
There is no clarity on how these guidelines are enforced. Within the guidance, it is clear that individuals’ privacy is of utmost importance. In the absence of knowledge, that means that the assumption should be that all are not yet vaccinated. Unless there is a way to reliably demonstrate vaccination status, it would likely still be safer to assume that there are individuals who are not fully vaccinated within the setting.
Finally, although this is great news surrounding the efficacy of the vaccine, some are concerned that local mask mandates that have already started to be lifted will be completely removed. As there is still a large portion of the population not yet fully vaccinated, it seems premature for local, state, and territorial authorities to lift these mandates.
How to continue exercising caution
With the outstanding concerns, I will continue to mask in settings, particularly indoors, where I do not definitely know that everyone is vaccinated. I will continue to do this to protect my children and my patients who are not yet vaccinated, and my patients who are immunosuppressed for whom we do not yet have enough information.
I will continue to advise my patients to be thoughtful about the risk for themselves and their families as well.
There has been more benefit to these public health measures then just decreased transmission of COVID-19. I hope that this year has reinforced within us the benefits of masking and self-isolation in the cases of any contagious illnesses.
Although I am looking forward to the opportunities to interact in person with more colleagues and friends, I think we should continue to do this with caution and thoughtfulness. We must be prepared for the possibility of vaccines having decreased efficacy against novel variants as well as eventually the possibility of waning immunity. If these should occur, we need to be prepared for additional recommendation changes and tightening of restrictions.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Interim Public Health Recommendations for Fully Vaccinated People. U.S. Department of Health & Human Services, May 13, 2021.
2. Centers for Disease Control and Prevention. Updated Healthcare Infection Prevention and Control Recommendations in Response to COVID-19 Vaccination. U.S. Department of Health and Human Services, April 27, 2021.
Use your court awareness to go faster in practice
Have you ever had a nightmare you’re running late? Recently I dreamt I was seeing patients on a ship, a little cruiser like the ones that give you tours of Boston Harbor, with low ceilings and narrow iron stairs. My nurse stood where what would have been the coffee and danish window. My first patient was a newborn (this was a nightmare, in case you forgot) who was enormous. She had a big belly and spindly legs that hung off the table. Uniform, umbilicated papules and pustules covered her body. At the sight of her, terror ripped through me – no clue. I rushed to the doctor lounge (nice the ship had one) and flipped channels on a little TV mounted on the ceiling. Suddenly, my nurse burst in, she was frantic because dozens of angry adults and crying children were crammed in the hallway. Apparently, I had been watching TV for hours and my whole clinic was now backed up.
Running-late dreams are common and usually relate to real life. For us, the clinic has been busy lately. Vaccinated patients are returning after a year with their skin cancers that have flourished and psoriasis covering them like kudzu. In particular, they “see the floor” better than other docs and therefore make continual adjustments to stay on pace. At its essence, they are using super-powers of observation to make decisions. It reminded me of a podcast about court awareness and great passers in basketball like the Charlotte Hornets’ LaMelo Ball and NBA great, Bill Bradley.
Bradley had an extraordinary ability to know where all the players were, and where they would be, at any given moment. He spent years honing this skill, noticing details in store windows as he stared straight ahead walking down a street. It’s reported his peripheral vision extended 5%-15% wider than average and he used it to gather more information and to process it more quickly. As a result he made outstanding decisions and fast, ultimately earning a spot in the Hall of Fame in Springfield.
Hall of Fame clinicians similarly take in a wider view than others and process that information quickly. They know how much time they have spent in the room, sense the emotional needs of the patient and anticipate the complexity of the problem. They quickly get to the critical questions and examinations that will make the diagnosis. They know the experience and skill of their medical assistant. They know the level of difficulty and even the temperament of patients who lie ahead on the schedule. All this is processed and used in moment-to-moment decision making. Do I sit down or stand up now? Can I excise this today, or reschedule? Do I ask another question? Do I step out of this room and see another in parallel while this biopsy is set up? And always, do I dare ask about grandkids or do I politely move on?
By broadening out their vision, they optimize their clinic, providing the best possible service, whether the day is busy or slow. I found their economy of motion also means they are less exhausted at the end of the day. I bet if when they dream of being on a ship, they’re sipping a Mai Tai, lounging on the deck.
For more on Bill Bradley and becoming more observant about your surroundings, you might appreciate the following:
www.newyorker.com/magazine/1965/01/23/a-sense-of-where-you-are and freakonomics.com/podcast/nsq-mindfulness/
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Have you ever had a nightmare you’re running late? Recently I dreamt I was seeing patients on a ship, a little cruiser like the ones that give you tours of Boston Harbor, with low ceilings and narrow iron stairs. My nurse stood where what would have been the coffee and danish window. My first patient was a newborn (this was a nightmare, in case you forgot) who was enormous. She had a big belly and spindly legs that hung off the table. Uniform, umbilicated papules and pustules covered her body. At the sight of her, terror ripped through me – no clue. I rushed to the doctor lounge (nice the ship had one) and flipped channels on a little TV mounted on the ceiling. Suddenly, my nurse burst in, she was frantic because dozens of angry adults and crying children were crammed in the hallway. Apparently, I had been watching TV for hours and my whole clinic was now backed up.
Running-late dreams are common and usually relate to real life. For us, the clinic has been busy lately. Vaccinated patients are returning after a year with their skin cancers that have flourished and psoriasis covering them like kudzu. In particular, they “see the floor” better than other docs and therefore make continual adjustments to stay on pace. At its essence, they are using super-powers of observation to make decisions. It reminded me of a podcast about court awareness and great passers in basketball like the Charlotte Hornets’ LaMelo Ball and NBA great, Bill Bradley.
Bradley had an extraordinary ability to know where all the players were, and where they would be, at any given moment. He spent years honing this skill, noticing details in store windows as he stared straight ahead walking down a street. It’s reported his peripheral vision extended 5%-15% wider than average and he used it to gather more information and to process it more quickly. As a result he made outstanding decisions and fast, ultimately earning a spot in the Hall of Fame in Springfield.
Hall of Fame clinicians similarly take in a wider view than others and process that information quickly. They know how much time they have spent in the room, sense the emotional needs of the patient and anticipate the complexity of the problem. They quickly get to the critical questions and examinations that will make the diagnosis. They know the experience and skill of their medical assistant. They know the level of difficulty and even the temperament of patients who lie ahead on the schedule. All this is processed and used in moment-to-moment decision making. Do I sit down or stand up now? Can I excise this today, or reschedule? Do I ask another question? Do I step out of this room and see another in parallel while this biopsy is set up? And always, do I dare ask about grandkids or do I politely move on?
By broadening out their vision, they optimize their clinic, providing the best possible service, whether the day is busy or slow. I found their economy of motion also means they are less exhausted at the end of the day. I bet if when they dream of being on a ship, they’re sipping a Mai Tai, lounging on the deck.
For more on Bill Bradley and becoming more observant about your surroundings, you might appreciate the following:
www.newyorker.com/magazine/1965/01/23/a-sense-of-where-you-are and freakonomics.com/podcast/nsq-mindfulness/
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Have you ever had a nightmare you’re running late? Recently I dreamt I was seeing patients on a ship, a little cruiser like the ones that give you tours of Boston Harbor, with low ceilings and narrow iron stairs. My nurse stood where what would have been the coffee and danish window. My first patient was a newborn (this was a nightmare, in case you forgot) who was enormous. She had a big belly and spindly legs that hung off the table. Uniform, umbilicated papules and pustules covered her body. At the sight of her, terror ripped through me – no clue. I rushed to the doctor lounge (nice the ship had one) and flipped channels on a little TV mounted on the ceiling. Suddenly, my nurse burst in, she was frantic because dozens of angry adults and crying children were crammed in the hallway. Apparently, I had been watching TV for hours and my whole clinic was now backed up.
Running-late dreams are common and usually relate to real life. For us, the clinic has been busy lately. Vaccinated patients are returning after a year with their skin cancers that have flourished and psoriasis covering them like kudzu. In particular, they “see the floor” better than other docs and therefore make continual adjustments to stay on pace. At its essence, they are using super-powers of observation to make decisions. It reminded me of a podcast about court awareness and great passers in basketball like the Charlotte Hornets’ LaMelo Ball and NBA great, Bill Bradley.
Bradley had an extraordinary ability to know where all the players were, and where they would be, at any given moment. He spent years honing this skill, noticing details in store windows as he stared straight ahead walking down a street. It’s reported his peripheral vision extended 5%-15% wider than average and he used it to gather more information and to process it more quickly. As a result he made outstanding decisions and fast, ultimately earning a spot in the Hall of Fame in Springfield.
Hall of Fame clinicians similarly take in a wider view than others and process that information quickly. They know how much time they have spent in the room, sense the emotional needs of the patient and anticipate the complexity of the problem. They quickly get to the critical questions and examinations that will make the diagnosis. They know the experience and skill of their medical assistant. They know the level of difficulty and even the temperament of patients who lie ahead on the schedule. All this is processed and used in moment-to-moment decision making. Do I sit down or stand up now? Can I excise this today, or reschedule? Do I ask another question? Do I step out of this room and see another in parallel while this biopsy is set up? And always, do I dare ask about grandkids or do I politely move on?
By broadening out their vision, they optimize their clinic, providing the best possible service, whether the day is busy or slow. I found their economy of motion also means they are less exhausted at the end of the day. I bet if when they dream of being on a ship, they’re sipping a Mai Tai, lounging on the deck.
For more on Bill Bradley and becoming more observant about your surroundings, you might appreciate the following:
www.newyorker.com/magazine/1965/01/23/a-sense-of-where-you-are and freakonomics.com/podcast/nsq-mindfulness/
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Addressing today’s racial health inequities requires understanding their roots
The health disparities seen in today’s high rates of Black infant and maternal morbidity and mortality are rooted in health inequities and generational stress dating back centuries in the United States, but today’s obstetricians can make changes in their own practices to address this inequity, according to Haywood L. Brown, MD, professor of ob.gyn. and associate dean of diversity at the Morsani College of Medicine and vice president of institutional equity at the University of South Florida, Tampa.
Dr. Brown delivered his remarks during the Benson and Pamela Harer Seminar on History at the annual meeting of the American College of Obstetricians and Gynecologists on May 2. His talk focused on the origins of perinatal and maternal health inequities and how those original factors play out today in increased maternal and neonatal morbidity and mortality among Black women and their babies.
“Racial and ethnic disparities and inequity in maternal and child health are prevalent and persistent. We have to move beyond the documentation,” Dr. Brown told attendees. “We have to adopt uniform care standards, recognizing our own biases and understanding that the contribution of social determinants of health are important in the care and outcome of women. And we have to work on decreasing the stress of women who give birth.”
Evelyn Nicole Mitchell, MD, faculty chair of the ob.gyn. diversity and inclusion committee at the University of Southern California, found Dr. Brown’s talk compelling and hopes it opens the eyes of others who attended.
“You really have to understand the why behind the problems we have, and it really goes back to slavery and this historical distrust that’s been here from the beginning,” Dr. Mitchell said in an interview. “I hope this allows people to open their eyes and think about this situation from their patients’ shoes, to really put their guard down and explore, ‘how can I contribute to fixing this system that has been here from the beginning?’ I think a lot of people get defensive and think: ‘Oh, I’m not a racist. I just don’t want to talk about this,’ but it’s about a system being racist.” The question then, Dr. Mitchell said, is: “So how do I contribute to that system?”
Dr. Brown frequently returned to the theme of high stress levels in Black mothers contributing to poorer outcomes, such as preterm birth. That stress arises originally from the generational stress brought on by racism and oppression over the centuries but has been compounded by poverty, racial injustice, lack of access to adequate nutrition, lower education levels, environmental factors, and other determinants of health.
“The bottom line, as Dr. Brown said, is that we need to decrease the stress level of Black mothers giving birth,” Dr. Mitchell said. “How can I, as a provider, decrease the stress level of my patients? Well, No. 1, I can identify and eliminate implicit bias that I may harbor.”
Slavery husbandry laid the groundwork for today
The most surprising aspect of Dr. Brown’s lecture for Dr. Mitchell was the fact that enslaved women received a measure of protection that other enslaved people did not to “ensure that they were healthy and that they were able to reproduce in the future,” Dr. Mitchell said. “It was for the wrong reasons – to keep slavery going – but in a sense they were prioritizing Black women to take advantage of their reproductive capacity, compared to nowadays where Black women are facing severe disparities.”
To safeguard enslaved women’s fecundity, plantation owners attempted to reduce stressors in the women’s lives, such as allowing them to cohabitate with a husband and nuclear family, though sexual assault and abuse still occurred. The owners also tracked the enslaved girls’ menstrual cycles after menarche to maximize their “breeding” potential, especially between the ages of 15 and 24. Slave owners delegated older enslaved women as maternity caregivers and midwives, leading to the passing down of midwifery skills through generations of Black American women.
“Pregnant women received the best medical care on the plantation because of the premium placed on reproduction,” Dr. Brown said. Wealthier planters called in doctors for complicated deliveries, which provided J. Marian Sims the ability conduct surgical experiments on Betsey, Lucy, and Anarcha to treat vesicovaginal fistula since fistula “limited her ability to do the maximum work she could in the house or on the plantation,” Dr. Brown said.
After slavery ended, health care access did not improve for Black people. In 1920, there was approximately 1 Black physician for every 3,000 Black people, compared with 1 in 500 for the White population, and grannie midwives continued to be the primary birthing attendants for Black women. Over the next several decades, however, both maternal and infant mortality across all races began steeply dropping. Reasons for the drop included the incorporation of the American Board of Obstetrics and Gynecology in 1930, a shift from home births to hospital births, and the legalization of abortion, which led to an 89% decline in deaths from septic illegal abortions from 1950 to 1973.
Still, Black maternal and infant mortality remained higher than White, and the poverty gap further exacerbated outcomes.
“Substandard maternity care really is the origin of many of the Black maternal and infant morbidity and mortality” complications, such as low birth weight, small for gestational age, growth restriction, and intrauterine starvation, “which we now believe are the origin of things like hypertension, diabetes, and obesity,” Dr. Brown said.
Today, inequities persist because of the systemic racism throughout this history.
“As we talk about health disparities, prematurity, growth restriction, and maternal morbidity, the fetal origins for adult disease in diabetes and hypertension and obesity have generational implications over the last 400 years,” Dr. Brown said. “Generational stress and stresses in lack women from slavery to present times are some of the origins of the things that we see today, including segregation, economic inequities, eugenic sterilizations, the quality of education, and of course, systemic racism on health care access and quality.”
It is this long arc of history that Dr. Mitchell hopes attendees will begin to grasp.
“If you don’t understand all that and have that depth, there’s no way for you to truly understand the problems that are going on and how to solve them,” Dr. Mitchell said. She hopes that especially those who have been more “resistant to accepting these truths” can start to see the big picture. “Hopefully, they can look at it as a systemic problem and then focus on how they can change the system.”
Dr Brown is a contributor to UpToDate and the Merck Manual and serves on the advisory boards of Merck for Mothers Global Women’s Health and BabyScripts. Dr. Mitchell has no disclosures.
The health disparities seen in today’s high rates of Black infant and maternal morbidity and mortality are rooted in health inequities and generational stress dating back centuries in the United States, but today’s obstetricians can make changes in their own practices to address this inequity, according to Haywood L. Brown, MD, professor of ob.gyn. and associate dean of diversity at the Morsani College of Medicine and vice president of institutional equity at the University of South Florida, Tampa.
Dr. Brown delivered his remarks during the Benson and Pamela Harer Seminar on History at the annual meeting of the American College of Obstetricians and Gynecologists on May 2. His talk focused on the origins of perinatal and maternal health inequities and how those original factors play out today in increased maternal and neonatal morbidity and mortality among Black women and their babies.
“Racial and ethnic disparities and inequity in maternal and child health are prevalent and persistent. We have to move beyond the documentation,” Dr. Brown told attendees. “We have to adopt uniform care standards, recognizing our own biases and understanding that the contribution of social determinants of health are important in the care and outcome of women. And we have to work on decreasing the stress of women who give birth.”
Evelyn Nicole Mitchell, MD, faculty chair of the ob.gyn. diversity and inclusion committee at the University of Southern California, found Dr. Brown’s talk compelling and hopes it opens the eyes of others who attended.
“You really have to understand the why behind the problems we have, and it really goes back to slavery and this historical distrust that’s been here from the beginning,” Dr. Mitchell said in an interview. “I hope this allows people to open their eyes and think about this situation from their patients’ shoes, to really put their guard down and explore, ‘how can I contribute to fixing this system that has been here from the beginning?’ I think a lot of people get defensive and think: ‘Oh, I’m not a racist. I just don’t want to talk about this,’ but it’s about a system being racist.” The question then, Dr. Mitchell said, is: “So how do I contribute to that system?”
Dr. Brown frequently returned to the theme of high stress levels in Black mothers contributing to poorer outcomes, such as preterm birth. That stress arises originally from the generational stress brought on by racism and oppression over the centuries but has been compounded by poverty, racial injustice, lack of access to adequate nutrition, lower education levels, environmental factors, and other determinants of health.
“The bottom line, as Dr. Brown said, is that we need to decrease the stress level of Black mothers giving birth,” Dr. Mitchell said. “How can I, as a provider, decrease the stress level of my patients? Well, No. 1, I can identify and eliminate implicit bias that I may harbor.”
Slavery husbandry laid the groundwork for today
The most surprising aspect of Dr. Brown’s lecture for Dr. Mitchell was the fact that enslaved women received a measure of protection that other enslaved people did not to “ensure that they were healthy and that they were able to reproduce in the future,” Dr. Mitchell said. “It was for the wrong reasons – to keep slavery going – but in a sense they were prioritizing Black women to take advantage of their reproductive capacity, compared to nowadays where Black women are facing severe disparities.”
To safeguard enslaved women’s fecundity, plantation owners attempted to reduce stressors in the women’s lives, such as allowing them to cohabitate with a husband and nuclear family, though sexual assault and abuse still occurred. The owners also tracked the enslaved girls’ menstrual cycles after menarche to maximize their “breeding” potential, especially between the ages of 15 and 24. Slave owners delegated older enslaved women as maternity caregivers and midwives, leading to the passing down of midwifery skills through generations of Black American women.
“Pregnant women received the best medical care on the plantation because of the premium placed on reproduction,” Dr. Brown said. Wealthier planters called in doctors for complicated deliveries, which provided J. Marian Sims the ability conduct surgical experiments on Betsey, Lucy, and Anarcha to treat vesicovaginal fistula since fistula “limited her ability to do the maximum work she could in the house or on the plantation,” Dr. Brown said.
After slavery ended, health care access did not improve for Black people. In 1920, there was approximately 1 Black physician for every 3,000 Black people, compared with 1 in 500 for the White population, and grannie midwives continued to be the primary birthing attendants for Black women. Over the next several decades, however, both maternal and infant mortality across all races began steeply dropping. Reasons for the drop included the incorporation of the American Board of Obstetrics and Gynecology in 1930, a shift from home births to hospital births, and the legalization of abortion, which led to an 89% decline in deaths from septic illegal abortions from 1950 to 1973.
Still, Black maternal and infant mortality remained higher than White, and the poverty gap further exacerbated outcomes.
“Substandard maternity care really is the origin of many of the Black maternal and infant morbidity and mortality” complications, such as low birth weight, small for gestational age, growth restriction, and intrauterine starvation, “which we now believe are the origin of things like hypertension, diabetes, and obesity,” Dr. Brown said.
Today, inequities persist because of the systemic racism throughout this history.
“As we talk about health disparities, prematurity, growth restriction, and maternal morbidity, the fetal origins for adult disease in diabetes and hypertension and obesity have generational implications over the last 400 years,” Dr. Brown said. “Generational stress and stresses in lack women from slavery to present times are some of the origins of the things that we see today, including segregation, economic inequities, eugenic sterilizations, the quality of education, and of course, systemic racism on health care access and quality.”
It is this long arc of history that Dr. Mitchell hopes attendees will begin to grasp.
“If you don’t understand all that and have that depth, there’s no way for you to truly understand the problems that are going on and how to solve them,” Dr. Mitchell said. She hopes that especially those who have been more “resistant to accepting these truths” can start to see the big picture. “Hopefully, they can look at it as a systemic problem and then focus on how they can change the system.”
Dr Brown is a contributor to UpToDate and the Merck Manual and serves on the advisory boards of Merck for Mothers Global Women’s Health and BabyScripts. Dr. Mitchell has no disclosures.
The health disparities seen in today’s high rates of Black infant and maternal morbidity and mortality are rooted in health inequities and generational stress dating back centuries in the United States, but today’s obstetricians can make changes in their own practices to address this inequity, according to Haywood L. Brown, MD, professor of ob.gyn. and associate dean of diversity at the Morsani College of Medicine and vice president of institutional equity at the University of South Florida, Tampa.
Dr. Brown delivered his remarks during the Benson and Pamela Harer Seminar on History at the annual meeting of the American College of Obstetricians and Gynecologists on May 2. His talk focused on the origins of perinatal and maternal health inequities and how those original factors play out today in increased maternal and neonatal morbidity and mortality among Black women and their babies.
“Racial and ethnic disparities and inequity in maternal and child health are prevalent and persistent. We have to move beyond the documentation,” Dr. Brown told attendees. “We have to adopt uniform care standards, recognizing our own biases and understanding that the contribution of social determinants of health are important in the care and outcome of women. And we have to work on decreasing the stress of women who give birth.”
Evelyn Nicole Mitchell, MD, faculty chair of the ob.gyn. diversity and inclusion committee at the University of Southern California, found Dr. Brown’s talk compelling and hopes it opens the eyes of others who attended.
“You really have to understand the why behind the problems we have, and it really goes back to slavery and this historical distrust that’s been here from the beginning,” Dr. Mitchell said in an interview. “I hope this allows people to open their eyes and think about this situation from their patients’ shoes, to really put their guard down and explore, ‘how can I contribute to fixing this system that has been here from the beginning?’ I think a lot of people get defensive and think: ‘Oh, I’m not a racist. I just don’t want to talk about this,’ but it’s about a system being racist.” The question then, Dr. Mitchell said, is: “So how do I contribute to that system?”
Dr. Brown frequently returned to the theme of high stress levels in Black mothers contributing to poorer outcomes, such as preterm birth. That stress arises originally from the generational stress brought on by racism and oppression over the centuries but has been compounded by poverty, racial injustice, lack of access to adequate nutrition, lower education levels, environmental factors, and other determinants of health.
“The bottom line, as Dr. Brown said, is that we need to decrease the stress level of Black mothers giving birth,” Dr. Mitchell said. “How can I, as a provider, decrease the stress level of my patients? Well, No. 1, I can identify and eliminate implicit bias that I may harbor.”
Slavery husbandry laid the groundwork for today
The most surprising aspect of Dr. Brown’s lecture for Dr. Mitchell was the fact that enslaved women received a measure of protection that other enslaved people did not to “ensure that they were healthy and that they were able to reproduce in the future,” Dr. Mitchell said. “It was for the wrong reasons – to keep slavery going – but in a sense they were prioritizing Black women to take advantage of their reproductive capacity, compared to nowadays where Black women are facing severe disparities.”
To safeguard enslaved women’s fecundity, plantation owners attempted to reduce stressors in the women’s lives, such as allowing them to cohabitate with a husband and nuclear family, though sexual assault and abuse still occurred. The owners also tracked the enslaved girls’ menstrual cycles after menarche to maximize their “breeding” potential, especially between the ages of 15 and 24. Slave owners delegated older enslaved women as maternity caregivers and midwives, leading to the passing down of midwifery skills through generations of Black American women.
“Pregnant women received the best medical care on the plantation because of the premium placed on reproduction,” Dr. Brown said. Wealthier planters called in doctors for complicated deliveries, which provided J. Marian Sims the ability conduct surgical experiments on Betsey, Lucy, and Anarcha to treat vesicovaginal fistula since fistula “limited her ability to do the maximum work she could in the house or on the plantation,” Dr. Brown said.
After slavery ended, health care access did not improve for Black people. In 1920, there was approximately 1 Black physician for every 3,000 Black people, compared with 1 in 500 for the White population, and grannie midwives continued to be the primary birthing attendants for Black women. Over the next several decades, however, both maternal and infant mortality across all races began steeply dropping. Reasons for the drop included the incorporation of the American Board of Obstetrics and Gynecology in 1930, a shift from home births to hospital births, and the legalization of abortion, which led to an 89% decline in deaths from septic illegal abortions from 1950 to 1973.
Still, Black maternal and infant mortality remained higher than White, and the poverty gap further exacerbated outcomes.
“Substandard maternity care really is the origin of many of the Black maternal and infant morbidity and mortality” complications, such as low birth weight, small for gestational age, growth restriction, and intrauterine starvation, “which we now believe are the origin of things like hypertension, diabetes, and obesity,” Dr. Brown said.
Today, inequities persist because of the systemic racism throughout this history.
“As we talk about health disparities, prematurity, growth restriction, and maternal morbidity, the fetal origins for adult disease in diabetes and hypertension and obesity have generational implications over the last 400 years,” Dr. Brown said. “Generational stress and stresses in lack women from slavery to present times are some of the origins of the things that we see today, including segregation, economic inequities, eugenic sterilizations, the quality of education, and of course, systemic racism on health care access and quality.”
It is this long arc of history that Dr. Mitchell hopes attendees will begin to grasp.
“If you don’t understand all that and have that depth, there’s no way for you to truly understand the problems that are going on and how to solve them,” Dr. Mitchell said. She hopes that especially those who have been more “resistant to accepting these truths” can start to see the big picture. “Hopefully, they can look at it as a systemic problem and then focus on how they can change the system.”
Dr Brown is a contributor to UpToDate and the Merck Manual and serves on the advisory boards of Merck for Mothers Global Women’s Health and BabyScripts. Dr. Mitchell has no disclosures.
FROM ACOG 2021
Lesions in pelvis may be ‘tip of the iceberg’ in endometriosis
Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).
Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.
“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.
Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.
Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.
Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.
One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”
Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.
Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.
In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.
Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.
During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.
“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.
Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.
Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.
Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).
Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.
“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.
Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.
Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.
Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.
One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”
Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.
Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.
In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.
Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.
During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.
“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.
Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.
Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.
Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).
Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.
“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.
Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.
Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.
Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.
One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”
Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.
Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.
In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.
Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.
During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.
“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.
Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.
Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.
FROM ACOG 2021
Primary ovarian insufficiency requires long-term management of sequelae
Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.
Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.
“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.
Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.
Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.
Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
Etiology of POI and associated conditions
A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.
Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.
Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.
Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.
“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.
To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:
- Menstrual irregularity for at least 3-4 months
- Test FSH and estradiol
- Test hCG, TSH, and prolactin
- If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.
However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
Long-term consequences of POI
Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.
“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
No interventions have been shown to increase ovarian activity
Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.
“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.
For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.
Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.
“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.
Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
Treatment of POI
Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.
The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.
Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.
Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”
Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.
Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.
Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.
“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.
Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.
Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.
Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
Etiology of POI and associated conditions
A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.
Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.
Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.
Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.
“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.
To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:
- Menstrual irregularity for at least 3-4 months
- Test FSH and estradiol
- Test hCG, TSH, and prolactin
- If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.
However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
Long-term consequences of POI
Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.
“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
No interventions have been shown to increase ovarian activity
Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.
“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.
For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.
Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.
“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.
Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
Treatment of POI
Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.
The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.
Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.
Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”
Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.
Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.
Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.
“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.
Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.
Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.
Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
Etiology of POI and associated conditions
A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.
Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.
Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.
Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.
“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.
To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:
- Menstrual irregularity for at least 3-4 months
- Test FSH and estradiol
- Test hCG, TSH, and prolactin
- If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.
However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
Long-term consequences of POI
Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.
“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
No interventions have been shown to increase ovarian activity
Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.
“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.
For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.
Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.
“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.
Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
Treatment of POI
Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.
The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.
Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.
Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”
Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.
FROM ACOG 2021
Heavy cannabis use in pregnancy correlates with risks to infant
Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.
Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.
The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.
Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”
Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.
The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
An increasingly common diagnosis
Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.
Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).
“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.
The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.
The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.
“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
Enough data to recommend abstaining
Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.
Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.
Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.
Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.
“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.
Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.
The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.
“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.
“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”
The study authors and Dr. Lo had no disclosures.
Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.
Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.
The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.
Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”
Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.
The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
An increasingly common diagnosis
Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.
Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).
“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.
The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.
The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.
“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
Enough data to recommend abstaining
Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.
Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.
Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.
Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.
“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.
Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.
The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.
“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.
“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”
The study authors and Dr. Lo had no disclosures.
Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.
Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.
The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.
Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”
Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.
The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
An increasingly common diagnosis
Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.
Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).
“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.
The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.
The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.
“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
Enough data to recommend abstaining
Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.
Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.
Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.
Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.
“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.
Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.
The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.
“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.
“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”
The study authors and Dr. Lo had no disclosures.
Dr. Fauci: Extraordinary challenges, scientific triumphs with COVID-19
“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.
“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.
“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
The general addresses the troops
Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.
Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
Epidemiology
The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.
“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.
According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
Virology and transmission
SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.
The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.
Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.
The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.
“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”
The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
Diagnostics
Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.
Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
Clinical course
The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.
Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.
Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.
People at increased risk for severe disease include older adults and those of any age with certain comorbidities.
Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.
In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.
In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.
Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
Therapeutics
Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.
Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
Vaccines
Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.
Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.
The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.
The real-world performance of these vaccines has been even more impressive, however.
For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.
He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.
Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
Horse race
Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.
“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.
“So, the message is: Get vaccinated,” he concluded.
“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.
“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.
“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
The general addresses the troops
Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.
Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
Epidemiology
The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.
“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.
According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
Virology and transmission
SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.
The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.
Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.
The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.
“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”
The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
Diagnostics
Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.
Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
Clinical course
The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.
Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.
Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.
People at increased risk for severe disease include older adults and those of any age with certain comorbidities.
Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.
In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.
In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.
Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
Therapeutics
Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.
Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
Vaccines
Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.
Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.
The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.
The real-world performance of these vaccines has been even more impressive, however.
For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.
He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.
Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
Horse race
Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.
“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.
“So, the message is: Get vaccinated,” he concluded.
“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.
“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.
“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
The general addresses the troops
Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.
Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
Epidemiology
The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.
“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.
According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
Virology and transmission
SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.
The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.
Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.
The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.
“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”
The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
Diagnostics
Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.
Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
Clinical course
The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.
Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.
Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.
People at increased risk for severe disease include older adults and those of any age with certain comorbidities.
Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.
In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.
In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.
Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
Therapeutics
Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.
Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
Vaccines
Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.
Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.
The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.
The real-world performance of these vaccines has been even more impressive, however.
For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.
He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.
Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
Horse race
Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.
“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.
“So, the message is: Get vaccinated,” he concluded.