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Long COVID associated with risk of metabolic liver disease
Postacute COVID syndrome (PACS), an ongoing inflammatory state following infection with SARS-CoV-2, is associated with greater risk of metabolic-associated fatty liver disease (MAFLD), according to an analysis of patients at a single clinic in Canada published in Open Forum Infectious Diseases.
MAFLD, also known as nonalcoholic fatty liver disease (NAFLD), is considered an indicator of general health and is in turn linked to greater risk of cardiovascular complications and mortality. It may be a multisystem disorder with various underlying causes.
PACS includes symptoms that affect various organ systems, with neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, psychological, sensory, and dermatologic clusters. An estimated 50%-80% of COVID-19 patients experience one or more clusters of symptoms 3 months after leaving the hospital.
But liver problems also appear in the acute phase, said Paul Martin, MD, who was asked to comment on the study. “Up to about half the patients during the acute illness may have elevated liver tests, but there seems to be a subset of patients in whom the abnormality persists. And then there are some reports in the literature of patients developing injury to their bile ducts in the liver over the long term, apparently as a consequence of COVID infection. What this paper suggests is that there may be some metabolic derangements associated with COVID infection, which in turn can accentuate or possibly cause fatty liver,” said Dr. Martin in an interview. He is chief of digestive health and liver diseases and a professor of medicine at the University of Miami.
“It highlights the need to get vaccinated against COVID and to take appropriate precautions because contracting the infection may lead to all sorts of consequences quite apart from having a respiratory illness,” said Dr. Martin.
The researchers retrospectively identified 235 patients hospitalized with COVID-19 between July 2020 and April 2021. Overall, 69% were men, and the median age was 61 years; 19.2% underwent mechanical ventilation and the mean duration of hospitalization was 11.7 days. They were seen for PACS symptoms a median 143 days after COVID-19 symptoms began, with 77.5% having symptoms of at least one PACS cluster. Of these clusters, 34.9% were neurocognitive, 53.2% were respiratory, 26.4% were musculoskeletal, 29.4% were psychological, 25.1% were dermatologic, and 17.5% were sensory.
At the later clinical visit for PACS symptoms, all patients underwent screening for MAFLD, which was defined as the presence of liver steatosis plus overweight/obesity or type 2 diabetes. Hepatic steatosis was determined from controlled attenuation parameter using transient elastrography. The analysis excluded patients with significant alcohol intake or hepatitis B or C. All patients with liver steatosis also had MAFLD, and this included 55.3% of the study population.
The hospital was able to obtain hepatic steatosis index (HSI) scores for 103 of 235 patients. Of these, 50% had MAFLD on admission for acute COVID-19, and 48.1% had MAFLD upon discharge based on this criterion. At the PACS follow-up visit, 71.3% were diagnosed with MAFLD. There was no statistically significant difference in the use of glucocorticoids or tocilizumab during hospitalization between those with and without MAFLD, and remdesivir use was insignificant in the patient population.
Given that the prevalence of MAFLD among the study population is more than double that in the general population, the authors suggest that MAFLD may be a new PACS cluster phenotype that could lead to long-term metabolic and cardiovascular complications. A potential explanation is loss of lean body mass during COVID-19 hospitalization followed by liver fat accumulation during recovery.
Other infections have also shown an association with increased MAFLD incidence, including HIV, Heliobacter pylori, and viral hepatitis. The authors worry that COVID-19 infection could exacerbate underlying conditions to a more severe MAFLD disease state.
The study is limited by a small sample size, limited follow-up, and the lack of a control group. Its retrospective nature leaves it vulnerable to biases.
“The natural history of MAFLD in the context of PACS is unknown at this time, and careful follow-up of these patients is needed to understand the clinical implications of this syndrome in the context of long COVID,” the authors wrote. “We speculate that [MAFLD] may be considered as an independent PACS-cluster phenotype, potentially affecting the metabolic and cardiovascular health of patients with PACS.”
One author has relationships with several pharmaceutical companies, but the remaining authors reported no conflicts of interest. Dr. Martin has no relevant financial disclosures.
Postacute COVID syndrome (PACS), an ongoing inflammatory state following infection with SARS-CoV-2, is associated with greater risk of metabolic-associated fatty liver disease (MAFLD), according to an analysis of patients at a single clinic in Canada published in Open Forum Infectious Diseases.
MAFLD, also known as nonalcoholic fatty liver disease (NAFLD), is considered an indicator of general health and is in turn linked to greater risk of cardiovascular complications and mortality. It may be a multisystem disorder with various underlying causes.
PACS includes symptoms that affect various organ systems, with neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, psychological, sensory, and dermatologic clusters. An estimated 50%-80% of COVID-19 patients experience one or more clusters of symptoms 3 months after leaving the hospital.
But liver problems also appear in the acute phase, said Paul Martin, MD, who was asked to comment on the study. “Up to about half the patients during the acute illness may have elevated liver tests, but there seems to be a subset of patients in whom the abnormality persists. And then there are some reports in the literature of patients developing injury to their bile ducts in the liver over the long term, apparently as a consequence of COVID infection. What this paper suggests is that there may be some metabolic derangements associated with COVID infection, which in turn can accentuate or possibly cause fatty liver,” said Dr. Martin in an interview. He is chief of digestive health and liver diseases and a professor of medicine at the University of Miami.
“It highlights the need to get vaccinated against COVID and to take appropriate precautions because contracting the infection may lead to all sorts of consequences quite apart from having a respiratory illness,” said Dr. Martin.
The researchers retrospectively identified 235 patients hospitalized with COVID-19 between July 2020 and April 2021. Overall, 69% were men, and the median age was 61 years; 19.2% underwent mechanical ventilation and the mean duration of hospitalization was 11.7 days. They were seen for PACS symptoms a median 143 days after COVID-19 symptoms began, with 77.5% having symptoms of at least one PACS cluster. Of these clusters, 34.9% were neurocognitive, 53.2% were respiratory, 26.4% were musculoskeletal, 29.4% were psychological, 25.1% were dermatologic, and 17.5% were sensory.
At the later clinical visit for PACS symptoms, all patients underwent screening for MAFLD, which was defined as the presence of liver steatosis plus overweight/obesity or type 2 diabetes. Hepatic steatosis was determined from controlled attenuation parameter using transient elastrography. The analysis excluded patients with significant alcohol intake or hepatitis B or C. All patients with liver steatosis also had MAFLD, and this included 55.3% of the study population.
The hospital was able to obtain hepatic steatosis index (HSI) scores for 103 of 235 patients. Of these, 50% had MAFLD on admission for acute COVID-19, and 48.1% had MAFLD upon discharge based on this criterion. At the PACS follow-up visit, 71.3% were diagnosed with MAFLD. There was no statistically significant difference in the use of glucocorticoids or tocilizumab during hospitalization between those with and without MAFLD, and remdesivir use was insignificant in the patient population.
Given that the prevalence of MAFLD among the study population is more than double that in the general population, the authors suggest that MAFLD may be a new PACS cluster phenotype that could lead to long-term metabolic and cardiovascular complications. A potential explanation is loss of lean body mass during COVID-19 hospitalization followed by liver fat accumulation during recovery.
Other infections have also shown an association with increased MAFLD incidence, including HIV, Heliobacter pylori, and viral hepatitis. The authors worry that COVID-19 infection could exacerbate underlying conditions to a more severe MAFLD disease state.
The study is limited by a small sample size, limited follow-up, and the lack of a control group. Its retrospective nature leaves it vulnerable to biases.
“The natural history of MAFLD in the context of PACS is unknown at this time, and careful follow-up of these patients is needed to understand the clinical implications of this syndrome in the context of long COVID,” the authors wrote. “We speculate that [MAFLD] may be considered as an independent PACS-cluster phenotype, potentially affecting the metabolic and cardiovascular health of patients with PACS.”
One author has relationships with several pharmaceutical companies, but the remaining authors reported no conflicts of interest. Dr. Martin has no relevant financial disclosures.
Postacute COVID syndrome (PACS), an ongoing inflammatory state following infection with SARS-CoV-2, is associated with greater risk of metabolic-associated fatty liver disease (MAFLD), according to an analysis of patients at a single clinic in Canada published in Open Forum Infectious Diseases.
MAFLD, also known as nonalcoholic fatty liver disease (NAFLD), is considered an indicator of general health and is in turn linked to greater risk of cardiovascular complications and mortality. It may be a multisystem disorder with various underlying causes.
PACS includes symptoms that affect various organ systems, with neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, psychological, sensory, and dermatologic clusters. An estimated 50%-80% of COVID-19 patients experience one or more clusters of symptoms 3 months after leaving the hospital.
But liver problems also appear in the acute phase, said Paul Martin, MD, who was asked to comment on the study. “Up to about half the patients during the acute illness may have elevated liver tests, but there seems to be a subset of patients in whom the abnormality persists. And then there are some reports in the literature of patients developing injury to their bile ducts in the liver over the long term, apparently as a consequence of COVID infection. What this paper suggests is that there may be some metabolic derangements associated with COVID infection, which in turn can accentuate or possibly cause fatty liver,” said Dr. Martin in an interview. He is chief of digestive health and liver diseases and a professor of medicine at the University of Miami.
“It highlights the need to get vaccinated against COVID and to take appropriate precautions because contracting the infection may lead to all sorts of consequences quite apart from having a respiratory illness,” said Dr. Martin.
The researchers retrospectively identified 235 patients hospitalized with COVID-19 between July 2020 and April 2021. Overall, 69% were men, and the median age was 61 years; 19.2% underwent mechanical ventilation and the mean duration of hospitalization was 11.7 days. They were seen for PACS symptoms a median 143 days after COVID-19 symptoms began, with 77.5% having symptoms of at least one PACS cluster. Of these clusters, 34.9% were neurocognitive, 53.2% were respiratory, 26.4% were musculoskeletal, 29.4% were psychological, 25.1% were dermatologic, and 17.5% were sensory.
At the later clinical visit for PACS symptoms, all patients underwent screening for MAFLD, which was defined as the presence of liver steatosis plus overweight/obesity or type 2 diabetes. Hepatic steatosis was determined from controlled attenuation parameter using transient elastrography. The analysis excluded patients with significant alcohol intake or hepatitis B or C. All patients with liver steatosis also had MAFLD, and this included 55.3% of the study population.
The hospital was able to obtain hepatic steatosis index (HSI) scores for 103 of 235 patients. Of these, 50% had MAFLD on admission for acute COVID-19, and 48.1% had MAFLD upon discharge based on this criterion. At the PACS follow-up visit, 71.3% were diagnosed with MAFLD. There was no statistically significant difference in the use of glucocorticoids or tocilizumab during hospitalization between those with and without MAFLD, and remdesivir use was insignificant in the patient population.
Given that the prevalence of MAFLD among the study population is more than double that in the general population, the authors suggest that MAFLD may be a new PACS cluster phenotype that could lead to long-term metabolic and cardiovascular complications. A potential explanation is loss of lean body mass during COVID-19 hospitalization followed by liver fat accumulation during recovery.
Other infections have also shown an association with increased MAFLD incidence, including HIV, Heliobacter pylori, and viral hepatitis. The authors worry that COVID-19 infection could exacerbate underlying conditions to a more severe MAFLD disease state.
The study is limited by a small sample size, limited follow-up, and the lack of a control group. Its retrospective nature leaves it vulnerable to biases.
“The natural history of MAFLD in the context of PACS is unknown at this time, and careful follow-up of these patients is needed to understand the clinical implications of this syndrome in the context of long COVID,” the authors wrote. “We speculate that [MAFLD] may be considered as an independent PACS-cluster phenotype, potentially affecting the metabolic and cardiovascular health of patients with PACS.”
One author has relationships with several pharmaceutical companies, but the remaining authors reported no conflicts of interest. Dr. Martin has no relevant financial disclosures.
FROM OPEN FORUM INFECTIOUS DISEASES
Phase 2 studies of novel JAK1 inhibitor for HS show promise
results from two small phase 2 studies showed.
“INCB054707 is an oral, small-molecule JAK1 inhibitor with approximately 52-fold greater selectivity for JAK1 versus JAK2,” researchers led by Afsaneh Alavi, MD, of the Mayo Clinic in Rochester, Minn., wrote in an article published recently in the British Journal of Dermatology. “Specifically targeting JAK1, a critical regulator of proinflammatory cytokine signaling implicated in several immune-related diseases, may reduce cytokine signaling involved in HS pathogenesis while limiting JAK2-mediated cytopenias.”
For the first study, 10 patients received 15 mg INCB054707 once daily for 8 weeks (NCT03569371). For the second study, 35 patients were randomized to 30, 60, or 90 mg INCB054707 once daily or placebo (3:1 within each cohort) for 8 weeks (NCT03607487). Eligibility criteria for both studies included patients with Hurley stage II/III HS who aged 18-75 years with lesions present in two or more anatomic locations, and a total abscess and inflammatory nodule count of three or more. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures.
The researchers reported that 30% of patients in study 1 and 42.3% of patients who received INCB054707 in study 2 experienced one or more treatment-emergent adverse event, most commonly upper respiratory tract infection. Among evaluable patients, 3 patients (42.9%) in study 1 and 17 patients in study 2 (65.4%) achieved HiSCR at week 8, compared with 57.1% of those in the placebo group. By dosing, 55.6% in the 30-mg group achieved HiSCR at week 8, compared with 55.6% in the 60-mg group and 87.5% in the 90-mg group.
“In conclusion, safety and efficacy findings from these two phase 2 studies establish proof of concept for the JAK1 inhibitor INCB054707 in the treatment of moderate to severe HS,” the authors wrote. “A phase 2, dose-ranging, placebo-controlled study exploring three dose levels and including approximately 200 patients is ongoing (NCT04476043) and expected to provide additional evidence of the safety and efficacy profile of INCB054707 in patients with HS.”
INCB054707 is being developed by Incyte Corporation. Dr. Alavi disclosed that she has received honoraria as a consultant or advisory board participant from AbbVie, Janssen, Novartis, Boehringer Ingelheim, InflaRX, and UCB, and received honoraria as an investigator for Boehringer Ingelheim and Processa.
results from two small phase 2 studies showed.
“INCB054707 is an oral, small-molecule JAK1 inhibitor with approximately 52-fold greater selectivity for JAK1 versus JAK2,” researchers led by Afsaneh Alavi, MD, of the Mayo Clinic in Rochester, Minn., wrote in an article published recently in the British Journal of Dermatology. “Specifically targeting JAK1, a critical regulator of proinflammatory cytokine signaling implicated in several immune-related diseases, may reduce cytokine signaling involved in HS pathogenesis while limiting JAK2-mediated cytopenias.”
For the first study, 10 patients received 15 mg INCB054707 once daily for 8 weeks (NCT03569371). For the second study, 35 patients were randomized to 30, 60, or 90 mg INCB054707 once daily or placebo (3:1 within each cohort) for 8 weeks (NCT03607487). Eligibility criteria for both studies included patients with Hurley stage II/III HS who aged 18-75 years with lesions present in two or more anatomic locations, and a total abscess and inflammatory nodule count of three or more. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures.
The researchers reported that 30% of patients in study 1 and 42.3% of patients who received INCB054707 in study 2 experienced one or more treatment-emergent adverse event, most commonly upper respiratory tract infection. Among evaluable patients, 3 patients (42.9%) in study 1 and 17 patients in study 2 (65.4%) achieved HiSCR at week 8, compared with 57.1% of those in the placebo group. By dosing, 55.6% in the 30-mg group achieved HiSCR at week 8, compared with 55.6% in the 60-mg group and 87.5% in the 90-mg group.
“In conclusion, safety and efficacy findings from these two phase 2 studies establish proof of concept for the JAK1 inhibitor INCB054707 in the treatment of moderate to severe HS,” the authors wrote. “A phase 2, dose-ranging, placebo-controlled study exploring three dose levels and including approximately 200 patients is ongoing (NCT04476043) and expected to provide additional evidence of the safety and efficacy profile of INCB054707 in patients with HS.”
INCB054707 is being developed by Incyte Corporation. Dr. Alavi disclosed that she has received honoraria as a consultant or advisory board participant from AbbVie, Janssen, Novartis, Boehringer Ingelheim, InflaRX, and UCB, and received honoraria as an investigator for Boehringer Ingelheim and Processa.
results from two small phase 2 studies showed.
“INCB054707 is an oral, small-molecule JAK1 inhibitor with approximately 52-fold greater selectivity for JAK1 versus JAK2,” researchers led by Afsaneh Alavi, MD, of the Mayo Clinic in Rochester, Minn., wrote in an article published recently in the British Journal of Dermatology. “Specifically targeting JAK1, a critical regulator of proinflammatory cytokine signaling implicated in several immune-related diseases, may reduce cytokine signaling involved in HS pathogenesis while limiting JAK2-mediated cytopenias.”
For the first study, 10 patients received 15 mg INCB054707 once daily for 8 weeks (NCT03569371). For the second study, 35 patients were randomized to 30, 60, or 90 mg INCB054707 once daily or placebo (3:1 within each cohort) for 8 weeks (NCT03607487). Eligibility criteria for both studies included patients with Hurley stage II/III HS who aged 18-75 years with lesions present in two or more anatomic locations, and a total abscess and inflammatory nodule count of three or more. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures.
The researchers reported that 30% of patients in study 1 and 42.3% of patients who received INCB054707 in study 2 experienced one or more treatment-emergent adverse event, most commonly upper respiratory tract infection. Among evaluable patients, 3 patients (42.9%) in study 1 and 17 patients in study 2 (65.4%) achieved HiSCR at week 8, compared with 57.1% of those in the placebo group. By dosing, 55.6% in the 30-mg group achieved HiSCR at week 8, compared with 55.6% in the 60-mg group and 87.5% in the 90-mg group.
“In conclusion, safety and efficacy findings from these two phase 2 studies establish proof of concept for the JAK1 inhibitor INCB054707 in the treatment of moderate to severe HS,” the authors wrote. “A phase 2, dose-ranging, placebo-controlled study exploring three dose levels and including approximately 200 patients is ongoing (NCT04476043) and expected to provide additional evidence of the safety and efficacy profile of INCB054707 in patients with HS.”
INCB054707 is being developed by Incyte Corporation. Dr. Alavi disclosed that she has received honoraria as a consultant or advisory board participant from AbbVie, Janssen, Novartis, Boehringer Ingelheim, InflaRX, and UCB, and received honoraria as an investigator for Boehringer Ingelheim and Processa.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
More than a month after launch, iPLEDGE glitches persist
which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.
When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.
The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.
And it’s not the answer, dermatologists said.
“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.
The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.
Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.
The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).
The problem is the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.
“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.
AADA: More recent efforts to improve the system
“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”
What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.
“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”
An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
Spotty progress
“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”
Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.
In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”
Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”
This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response.
Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This story was updated on 1/24/22.
which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.
When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.
The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.
And it’s not the answer, dermatologists said.
“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.
The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.
Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.
The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).
The problem is the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.
“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.
AADA: More recent efforts to improve the system
“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”
What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.
“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”
An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
Spotty progress
“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”
Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.
In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”
Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”
This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response.
Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This story was updated on 1/24/22.
which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.
When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.
The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.
And it’s not the answer, dermatologists said.
“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.
The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.
Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.
The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).
The problem is the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.
“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.
AADA: More recent efforts to improve the system
“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”
What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.
“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”
An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
Spotty progress
“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”
Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.
In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”
Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”
This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response.
Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This story was updated on 1/24/22.
Intensive weight loss fails to help women with obesity and infertility
An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.
Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.
The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.
In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.
The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.
The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.
Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).
First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.
Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.
However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.
Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.
“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
Data may inform patient discussions
The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.
According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.
In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.
The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.
The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.
Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.
“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”
The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.
An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.
Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.
The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.
In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.
The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.
The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.
Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).
First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.
Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.
However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.
Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.
“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
Data may inform patient discussions
The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.
According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.
In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.
The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.
The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.
Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.
“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”
The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.
An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.
Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.
The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.
In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.
The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.
The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.
Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).
First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.
Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.
However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.
Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.
“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
Data may inform patient discussions
The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.
According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.
In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.
The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.
The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.
Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.
“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”
The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.
FROM PLOS MEDICINE
Learning a growth mindset
“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.
The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?
I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.
My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.
The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.
Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.
Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?
Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.
The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?
I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.
My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.
The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.
Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.
Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?
Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.
The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?
I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.
My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.
The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.
Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.
Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?
Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
100 coauthored papers, 10 years: Cancer transplant pioneers model 'team science'
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
Peanut oral immunotherapy is safe and effective in toddlers in large placebo-controlled trial
In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.
About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.
Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.
In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.
“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”
The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.
In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.
There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”
In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.
On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.
While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”
On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.
Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”
Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.
Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”
Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.
A version of this article first appeared on Medscape.com.
In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.
About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.
Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.
In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.
“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”
The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.
In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.
There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”
In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.
On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.
While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”
On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.
Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”
Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.
Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”
Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.
A version of this article first appeared on Medscape.com.
In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.
About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.
Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.
In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.
“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”
The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.
In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.
There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”
In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.
On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.
While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”
On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.
Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”
Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.
Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”
Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.
A version of this article first appeared on Medscape.com.
Things reproductive psychiatrists might ‘always’ or ‘never’ do in 2022
The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.
The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.
To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
Things we ‘always’ do
1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.
Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.
2. I almost always treat with consistency of medication across the peripartum period.
Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).
3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.
We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.
4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.
Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.
We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.
5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.
We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.
The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.
The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
Things we ‘never’ do
1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).
Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.
We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.
We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.
2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.
Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.
3. We never switch antidepressants once a woman has become pregnant.
Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.
If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
Final thoughts
Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.
The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.
To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
Things we ‘always’ do
1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.
Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.
2. I almost always treat with consistency of medication across the peripartum period.
Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).
3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.
We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.
4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.
Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.
We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.
5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.
We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.
The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.
The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
Things we ‘never’ do
1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).
Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.
We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.
We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.
2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.
Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.
3. We never switch antidepressants once a woman has become pregnant.
Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.
If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
Final thoughts
Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.
The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.
To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
Things we ‘always’ do
1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.
Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.
2. I almost always treat with consistency of medication across the peripartum period.
Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).
3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.
We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.
4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.
Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.
We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.
5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.
We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.
The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.
The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
Things we ‘never’ do
1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).
Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.
We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.
We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.
2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.
Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.
3. We never switch antidepressants once a woman has become pregnant.
Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.
If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
Final thoughts
Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Survey shows more women drinking during pregnancy
More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.
The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.
That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.
“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”
Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.
Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”
The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.
According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.
The increase within the 3-year period was roughly the same as in previous surveys.
“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.
“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.
Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”
Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”
Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.
That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.
The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.
So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”
A version of this article first appeared on Medscape.com.
More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.
The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.
That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.
“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”
Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.
Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”
The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.
According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.
The increase within the 3-year period was roughly the same as in previous surveys.
“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.
“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.
Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”
Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”
Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.
That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.
The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.
So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”
A version of this article first appeared on Medscape.com.
More pregnant Americans indulged – and overindulged – in alcohol from 2018 to 2020 than in previous years, but researchers found no sharp increase associated with the first wave of COVID-19 lockdowns, according to a new report from the Centers for Disease Control and Prevention.
The pandemic notwithstanding, health officials worry about a rising tide of pregnant women using alcohol and binge drinking since the CDC survey began in 2011. In the period ending in 2013, 1 in 10 women reported having had a drink in the previous 30 days; by 2017, that figure was 1 in 9; and in the latest survey, the number had risen to 1 in 7.
That mark is “the highest to date,” said Lucas Gosdin, PhD, MPH, an epidemic intelligence officer at the CDC’s National Center on Birth Defects and Developmental Disabilities, Atlanta, and first author of the report, which was published in Morbidity and Mortality Weekly Report.
“We’re concerned that this number has been slowly increasing,” Amanda Cohn, MD, director of the CDC’s Division of Birth Defects and Infant Disorders, told this news organization. “We need to be doing more outreach, both to pregnant persons as well as health care providers who are caring for them.”
Exposure to alcohol in the womb has been linked to a wide range of neurologic and physical problems in children, ranging from fetal alcohol syndrome to stunted learning abilities. Even if these problems are unlikely, experts insist there’s no known “safe” amount of alcohol a pregnant woman can have.
Dr. Cohn likened alcohol use to that of tobacco. “Lots of people smoke who don’t get lung cancer. Still, everyone is at an increased risk,” she said. “The safest way to not get lung cancer is to not smoke at all. It’s a behavior that can prevent additional harm.”
The report summarizes the results of a phone survey of 6,327 pregnant Americans between the ages of 18 and 49. The survey asked whether women had consumed an alcoholic beverage or had at least four drinks on one occasion – a common definition of binge drinking – in the past 30 days.
According to the report, 13.5% of women reported using alcohol, and 5.2% said they had binged on alcohol. Women who experienced frequent mental distress – describing their mental health as “not good” for 14 or more days in the past month – were twice as likely to drink and three times likelier to binge drink, the researchers found.
The increase within the 3-year period was roughly the same as in previous surveys.
“There was no evidence of increased alcohol consumption by pregnant adults in 2020 relative to 2019, despite possible increased alcohol sales and consumption among the general population during the first months of the COVID-19 pandemic,” the report states.
“That is one finding that was unexpected but that we were pleased to see,” Dr. Gosdin said.
Experts stressed that the survey covered only the first 9 months of the COVID-19 pandemic. “We’re still in the depths of it,” Samuel T. Bauer, MD, associate professor of obstetrics and gynecology at Duke University Medical Center, Durham, N.C., told this news organization. “People with alcohol use disorders certainly have been challenged during COVID. I think this is a preliminary answer.”
Dr. Gosdin said the effects of the pandemic on drinking habits bear watching. “We are concerned about the impacts of COVID-19,” he said. “We know it’s affected how people access regular care.”
Although virtual care has “exploded during COVID,” Dr. Bauer said, insurers have “turned off reimbursing” for doctor-patient visits via telephone, but not for visits by Internet-based video platforms like Zoom.
That split creates equity issues in many parts of the country, including his home state of North Carolina, where broadband is scarce, and patients may live 100 miles or more away from caregivers.
The “full-blown birth defect” of fetal alcohol syndrome is just the most visible hazard of drinking. Other medical and developmental issues include speech delays, slower learning and reading skills, attention-deficit and hyperactivity disorders, and problems with the heart and kidneys.
So, when Dr. Bauer encounters patients who believe that a few drinks will not harm their baby, he says he tells them: “’Why is this going to be where you put your flag?’ That leads to a different form of conversation.”
A version of this article first appeared on Medscape.com.
FROM MMWR
High-risk women–What breast screening is appropriate?
Text copyright DenseBreast-info.org.
Answer
B. For a 28-year-old woman, herself untested, with a known pathogenic BRCA1 or BRCA2 mutation in a first-degree relative (mother/ father, sister/brother, daughter/son), screening annual magnetic resonance imaging (MRI) alone is recommended until age 30, followed by screening annual MRI and mammography/tomosynthesis at age 30 and beyond. If MRI is not an option, ultrasonography or contrast-enhanced mammography should be considered.
Most medical societies in the United States recommend mammography screening beginning at age 40 if a woman is at average risk. If a woman is determined to be at high risk, breast cancer screening may be recommended to begin by age 30. Breast cancer risk assessment, with a risk model based largely on family history, should begin by age 30 for all women.
The American College of Radiology (ACR),1 National Comprehensive Cancer Network (NCCN),2,3 and American Society of Breast Surgeons recommend annual MRI screening for the following high-risk subgroups of women:
- Women with known disease-causing BRCA1 or BRCA2 mutations, or other disease-causing mutations, or their untested first-degree relatives. (Age to begin screening MRI and screening mammography/tomosynthesis varies by mutation).1,3 Women with known pathogenic BRCA1 or BRCA2 mutations, or their untested first-degree relatives, should begin annual screening with MRI only between ages 25-29, adding annual digital mammography/tomosynthesis at age 30 and beyond (unless the woman has had bilateral mastectomy). Note: There is emerging evidence that the benefit of mammography is relatively small in pathogenic BRCA1 carriers prior to the age of 40; therefore, the ACR suggests BRCA1 mutation carriers may consider delaying mammography until age 40 only if they receive contrast-enhanced MRI annually starting at age 25.1 Annual mammography is of benefit beginning at age 30 in those with BRCA2 or other disease-causing mutations.Age to begin annual MRI screening and mammography/tomosynthesis in women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome [TP53]; Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome [PTEN]; hereditary diffuse gastric cancer [CDH1]; Peutz-Jeghers syndrome [STK11]; neurofibromatosis type 1 [NF1]; PALB2; ATM; CHEK2; or BARD1) ranges from 20-40 years depending on the mutation and family history.3 (See https://densebreast-info.org/providers-faqs /what-is-the-screening-management-for -various-other-mutation-carriers/.)
- Women who received chest/mantle radiation therapy by age 30 (such as for Hodgkin disease) and at least 8 years prior. Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,1,2,4,5 with risk similar in magnitude to BRCA1 or BRCA2 carriers, and are recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.
- Women with a calculated lifetime risk of breast cancer of ≥20% are recommended to begin annual screening MRI by age 25-30.1,2,5 Any of the models that include detailed family history such as the Tyrer-Cuzick (IBIS, which now includes breast density as a risk factor); BRCAPRO; BOADICEA; Claus; or Penn II; but not the Gail or Breast Cancer Surveillance Consortium (BCSC) models, can be used to estimate lifetime risk for the purposes of screening MRI guidelines. (See https://densebreast -info.org/for-providers/risk-model-tutorial/ for a summary table with live links.)
- Women with a personal history of breast cancer and dense breasts or diagnosis by age 50, regardless of breast density. A personal history of breast cancer is not included in risk models, but all women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥20% lifetime risk for a new breast cancer.1,2 Annual MRI may be considered in addition to annual mammography or tomosynthesis in women with a personal history of breast cancer diagnosed after age 50 and without dense breasts, and/or a history of lobular carcinoma in situ (LCIS) or prior atypia (eg, atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or atypical papilloma).1,2
Supplemental MRI screening should continue until age 75, after which management should be considered on an individual basis. If MRI screening is not an option, ultrasound or contrast-enhanced mammography (where available) should be considered as an alternative.6-8 ●
For more information, visit medically sourced DenseBreastinfo.org. Comprehensive resources include a free CME opportunity, Dense Breasts and Supplemental Screening.
- Monticciolo DL, Newell MS, Moy L, et al. Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. J Am Coll Radiol. 2018;15 (3 Pt A):408-414. doi: 10.1016/j.jacr.2017.11.034.
- National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis (Version 1.2021). https://www .nccn.org/professionals/physician_gls/pdf/breast-screening .pdf. Accessed November 18, 2021.
- National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf /genetics_bop.pdf. Accessed July 31, 2020.
- Oeffinger KC, Ford JS, Moskowitz CS, et al. Breast cancer surveillance practices among women previously treated with chest radiation for a childhood cancer. JAMA. 2009;301(4):404-414. DOI: 10.1001/jama.2008.1039.
- Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89. doi: 10.3322/canjclin.57.2.75.
- Sorin V, Yagil Y, Yosepovich A, et al. Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts. AJR Am J Roentgenol. 2018;211:W267-W274. doi: 10.2214/AJR.17.19355.
- Sung JS, Lebron L, Keating D, et al. Performance of dualenergy contrast-enhanced digital mammography for screening women at increased risk of breast cancer. Radiology. 2019;293:81-88. doi: 10.1148/radiol.2019182660.
- Xiang W, Rao H, Zhou L. A meta-analysis of contrastenhanced spectral mammography versus MRI in the diagnosis of breast cancer. Thorac Cancer. 2020;11:1423-1432. doi: 10.1111/1759-7714.13400.
Text copyright DenseBreast-info.org.
Answer
B. For a 28-year-old woman, herself untested, with a known pathogenic BRCA1 or BRCA2 mutation in a first-degree relative (mother/ father, sister/brother, daughter/son), screening annual magnetic resonance imaging (MRI) alone is recommended until age 30, followed by screening annual MRI and mammography/tomosynthesis at age 30 and beyond. If MRI is not an option, ultrasonography or contrast-enhanced mammography should be considered.
Most medical societies in the United States recommend mammography screening beginning at age 40 if a woman is at average risk. If a woman is determined to be at high risk, breast cancer screening may be recommended to begin by age 30. Breast cancer risk assessment, with a risk model based largely on family history, should begin by age 30 for all women.
The American College of Radiology (ACR),1 National Comprehensive Cancer Network (NCCN),2,3 and American Society of Breast Surgeons recommend annual MRI screening for the following high-risk subgroups of women:
- Women with known disease-causing BRCA1 or BRCA2 mutations, or other disease-causing mutations, or their untested first-degree relatives. (Age to begin screening MRI and screening mammography/tomosynthesis varies by mutation).1,3 Women with known pathogenic BRCA1 or BRCA2 mutations, or their untested first-degree relatives, should begin annual screening with MRI only between ages 25-29, adding annual digital mammography/tomosynthesis at age 30 and beyond (unless the woman has had bilateral mastectomy). Note: There is emerging evidence that the benefit of mammography is relatively small in pathogenic BRCA1 carriers prior to the age of 40; therefore, the ACR suggests BRCA1 mutation carriers may consider delaying mammography until age 40 only if they receive contrast-enhanced MRI annually starting at age 25.1 Annual mammography is of benefit beginning at age 30 in those with BRCA2 or other disease-causing mutations.Age to begin annual MRI screening and mammography/tomosynthesis in women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome [TP53]; Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome [PTEN]; hereditary diffuse gastric cancer [CDH1]; Peutz-Jeghers syndrome [STK11]; neurofibromatosis type 1 [NF1]; PALB2; ATM; CHEK2; or BARD1) ranges from 20-40 years depending on the mutation and family history.3 (See https://densebreast-info.org/providers-faqs /what-is-the-screening-management-for -various-other-mutation-carriers/.)
- Women who received chest/mantle radiation therapy by age 30 (such as for Hodgkin disease) and at least 8 years prior. Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,1,2,4,5 with risk similar in magnitude to BRCA1 or BRCA2 carriers, and are recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.
- Women with a calculated lifetime risk of breast cancer of ≥20% are recommended to begin annual screening MRI by age 25-30.1,2,5 Any of the models that include detailed family history such as the Tyrer-Cuzick (IBIS, which now includes breast density as a risk factor); BRCAPRO; BOADICEA; Claus; or Penn II; but not the Gail or Breast Cancer Surveillance Consortium (BCSC) models, can be used to estimate lifetime risk for the purposes of screening MRI guidelines. (See https://densebreast -info.org/for-providers/risk-model-tutorial/ for a summary table with live links.)
- Women with a personal history of breast cancer and dense breasts or diagnosis by age 50, regardless of breast density. A personal history of breast cancer is not included in risk models, but all women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥20% lifetime risk for a new breast cancer.1,2 Annual MRI may be considered in addition to annual mammography or tomosynthesis in women with a personal history of breast cancer diagnosed after age 50 and without dense breasts, and/or a history of lobular carcinoma in situ (LCIS) or prior atypia (eg, atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or atypical papilloma).1,2
Supplemental MRI screening should continue until age 75, after which management should be considered on an individual basis. If MRI screening is not an option, ultrasound or contrast-enhanced mammography (where available) should be considered as an alternative.6-8 ●
For more information, visit medically sourced DenseBreastinfo.org. Comprehensive resources include a free CME opportunity, Dense Breasts and Supplemental Screening.
Text copyright DenseBreast-info.org.
Answer
B. For a 28-year-old woman, herself untested, with a known pathogenic BRCA1 or BRCA2 mutation in a first-degree relative (mother/ father, sister/brother, daughter/son), screening annual magnetic resonance imaging (MRI) alone is recommended until age 30, followed by screening annual MRI and mammography/tomosynthesis at age 30 and beyond. If MRI is not an option, ultrasonography or contrast-enhanced mammography should be considered.
Most medical societies in the United States recommend mammography screening beginning at age 40 if a woman is at average risk. If a woman is determined to be at high risk, breast cancer screening may be recommended to begin by age 30. Breast cancer risk assessment, with a risk model based largely on family history, should begin by age 30 for all women.
The American College of Radiology (ACR),1 National Comprehensive Cancer Network (NCCN),2,3 and American Society of Breast Surgeons recommend annual MRI screening for the following high-risk subgroups of women:
- Women with known disease-causing BRCA1 or BRCA2 mutations, or other disease-causing mutations, or their untested first-degree relatives. (Age to begin screening MRI and screening mammography/tomosynthesis varies by mutation).1,3 Women with known pathogenic BRCA1 or BRCA2 mutations, or their untested first-degree relatives, should begin annual screening with MRI only between ages 25-29, adding annual digital mammography/tomosynthesis at age 30 and beyond (unless the woman has had bilateral mastectomy). Note: There is emerging evidence that the benefit of mammography is relatively small in pathogenic BRCA1 carriers prior to the age of 40; therefore, the ACR suggests BRCA1 mutation carriers may consider delaying mammography until age 40 only if they receive contrast-enhanced MRI annually starting at age 25.1 Annual mammography is of benefit beginning at age 30 in those with BRCA2 or other disease-causing mutations.Age to begin annual MRI screening and mammography/tomosynthesis in women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations (such as those associated with Li-Fraumeni syndrome [TP53]; Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome [PTEN]; hereditary diffuse gastric cancer [CDH1]; Peutz-Jeghers syndrome [STK11]; neurofibromatosis type 1 [NF1]; PALB2; ATM; CHEK2; or BARD1) ranges from 20-40 years depending on the mutation and family history.3 (See https://densebreast-info.org/providers-faqs /what-is-the-screening-management-for -various-other-mutation-carriers/.)
- Women who received chest/mantle radiation therapy by age 30 (such as for Hodgkin disease) and at least 8 years prior. Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer,1,2,4,5 with risk similar in magnitude to BRCA1 or BRCA2 carriers, and are recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.
- Women with a calculated lifetime risk of breast cancer of ≥20% are recommended to begin annual screening MRI by age 25-30.1,2,5 Any of the models that include detailed family history such as the Tyrer-Cuzick (IBIS, which now includes breast density as a risk factor); BRCAPRO; BOADICEA; Claus; or Penn II; but not the Gail or Breast Cancer Surveillance Consortium (BCSC) models, can be used to estimate lifetime risk for the purposes of screening MRI guidelines. (See https://densebreast -info.org/for-providers/risk-model-tutorial/ for a summary table with live links.)
- Women with a personal history of breast cancer and dense breasts or diagnosis by age 50, regardless of breast density. A personal history of breast cancer is not included in risk models, but all women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥20% lifetime risk for a new breast cancer.1,2 Annual MRI may be considered in addition to annual mammography or tomosynthesis in women with a personal history of breast cancer diagnosed after age 50 and without dense breasts, and/or a history of lobular carcinoma in situ (LCIS) or prior atypia (eg, atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or atypical papilloma).1,2
Supplemental MRI screening should continue until age 75, after which management should be considered on an individual basis. If MRI screening is not an option, ultrasound or contrast-enhanced mammography (where available) should be considered as an alternative.6-8 ●
For more information, visit medically sourced DenseBreastinfo.org. Comprehensive resources include a free CME opportunity, Dense Breasts and Supplemental Screening.
- Monticciolo DL, Newell MS, Moy L, et al. Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. J Am Coll Radiol. 2018;15 (3 Pt A):408-414. doi: 10.1016/j.jacr.2017.11.034.
- National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis (Version 1.2021). https://www .nccn.org/professionals/physician_gls/pdf/breast-screening .pdf. Accessed November 18, 2021.
- National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf /genetics_bop.pdf. Accessed July 31, 2020.
- Oeffinger KC, Ford JS, Moskowitz CS, et al. Breast cancer surveillance practices among women previously treated with chest radiation for a childhood cancer. JAMA. 2009;301(4):404-414. DOI: 10.1001/jama.2008.1039.
- Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89. doi: 10.3322/canjclin.57.2.75.
- Sorin V, Yagil Y, Yosepovich A, et al. Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts. AJR Am J Roentgenol. 2018;211:W267-W274. doi: 10.2214/AJR.17.19355.
- Sung JS, Lebron L, Keating D, et al. Performance of dualenergy contrast-enhanced digital mammography for screening women at increased risk of breast cancer. Radiology. 2019;293:81-88. doi: 10.1148/radiol.2019182660.
- Xiang W, Rao H, Zhou L. A meta-analysis of contrastenhanced spectral mammography versus MRI in the diagnosis of breast cancer. Thorac Cancer. 2020;11:1423-1432. doi: 10.1111/1759-7714.13400.
- Monticciolo DL, Newell MS, Moy L, et al. Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. J Am Coll Radiol. 2018;15 (3 Pt A):408-414. doi: 10.1016/j.jacr.2017.11.034.
- National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis (Version 1.2021). https://www .nccn.org/professionals/physician_gls/pdf/breast-screening .pdf. Accessed November 18, 2021.
- National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf /genetics_bop.pdf. Accessed July 31, 2020.
- Oeffinger KC, Ford JS, Moskowitz CS, et al. Breast cancer surveillance practices among women previously treated with chest radiation for a childhood cancer. JAMA. 2009;301(4):404-414. DOI: 10.1001/jama.2008.1039.
- Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89. doi: 10.3322/canjclin.57.2.75.
- Sorin V, Yagil Y, Yosepovich A, et al. Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts. AJR Am J Roentgenol. 2018;211:W267-W274. doi: 10.2214/AJR.17.19355.
- Sung JS, Lebron L, Keating D, et al. Performance of dualenergy contrast-enhanced digital mammography for screening women at increased risk of breast cancer. Radiology. 2019;293:81-88. doi: 10.1148/radiol.2019182660.
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