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Studies address ibrutinib bleeding risk in patients with CLL receiving Mohs surgery
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE ACMS ANNUAL MEETING
Immunotherapy now first line for esophageal cancer
The new approval for the drug, a programmed cell death–ligand-1 inhibitor, is for use in this patient population regardless of PD-L1 status.
The indication also specifies that nivolumab is to be used together with chemotherapy (with a fluoropyrimidine- and platinum-containing regimen) or in combination with ipilimumab (Yervoy), an immunotherapy with a different mechanism of action.
“Today’s approvals bring two first-line immunotherapy-based treatment options at once ... to newly diagnosed patients with unresectable advanced or metastatic ESCC,” commented Adam Lenkowsky, a senior vice president at Bristol-Myers Squibb, which makes both nivolumab and ipilimumab.
The approval of the new indication by the Food and Drug Administration was based on improved survival shown in the phase 3 CheckMate-648 trial, which involved nearly 1,000 patients. The trial had three arms and compared nivolumab plus chemotherapy (n = 321) and nivolumab plus ipilimumab (n = 324) with chemotherapy alone (n = 324).
The results showed improved survival with both nivolumab combinations compared with chemotherapy (fluorouracil and cisplatin) alone. Overall survival was improved both in all randomized patients (a secondary endpoint) and in patients whose tumors expressed PD-L1 (≥ 1%), the primary endpoint.
For the combination of nivolumab plus chemotherapy, median overall survival was 13.2 versus 10.7 months, compared with chemotherapy alone in all randomized patients, and 15.4 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
For the combination of nivolumab plus ipilimumab, median overall survival was 12.8 versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
However, progression-free survival did not reach statistical significance in any group.
“Unresectable advanced or metastatic ESCC is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting,” commented Jaffer A. Ajani, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center, Houston. He was also the lead U.S. investigator for CheckMate-648 and, in a company press release, said the “two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”
Results from the trial were presented at the 2021 annual meeting of the American Society of Clinical Oncology. At that time, trial investigator Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, England, told attendees that “nivolumab plus chemotherapy and nivolumab plus ipilimumab each represent a new potential first-line standard of care for patients with advanced ESCC.”
Commenting on that presentation, Samuel J. Klempner, MD, a gastrointestinal medical oncologist at the Massachusetts General Hospital Cancer Center, Boston, noted that the “prospect of a chemo-free regimen for advanced ESCC with the well-studied combination of ipilimumab and nivolumab would represent a welcome addition to our treatment armamentarium.”
No new safety signals
Dr. Chau noted there were no new safety signals with either of the immunotherapies.
Nivolumab and/or chemotherapy were discontinued in 39% of patients and delayed in 71% of patients for an adverse reaction.
Nivolumab and/or ipilimumab were discontinued in 23% of patients and delayed in 46% of patients for an adverse reaction.
The manufacturer cautioned that immunotherapy with nivolumab with or without ipilimumab has been associated with severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, and infusion-related reactions.
A version of this article first appeared on Medscape.com.
The new approval for the drug, a programmed cell death–ligand-1 inhibitor, is for use in this patient population regardless of PD-L1 status.
The indication also specifies that nivolumab is to be used together with chemotherapy (with a fluoropyrimidine- and platinum-containing regimen) or in combination with ipilimumab (Yervoy), an immunotherapy with a different mechanism of action.
“Today’s approvals bring two first-line immunotherapy-based treatment options at once ... to newly diagnosed patients with unresectable advanced or metastatic ESCC,” commented Adam Lenkowsky, a senior vice president at Bristol-Myers Squibb, which makes both nivolumab and ipilimumab.
The approval of the new indication by the Food and Drug Administration was based on improved survival shown in the phase 3 CheckMate-648 trial, which involved nearly 1,000 patients. The trial had three arms and compared nivolumab plus chemotherapy (n = 321) and nivolumab plus ipilimumab (n = 324) with chemotherapy alone (n = 324).
The results showed improved survival with both nivolumab combinations compared with chemotherapy (fluorouracil and cisplatin) alone. Overall survival was improved both in all randomized patients (a secondary endpoint) and in patients whose tumors expressed PD-L1 (≥ 1%), the primary endpoint.
For the combination of nivolumab plus chemotherapy, median overall survival was 13.2 versus 10.7 months, compared with chemotherapy alone in all randomized patients, and 15.4 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
For the combination of nivolumab plus ipilimumab, median overall survival was 12.8 versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
However, progression-free survival did not reach statistical significance in any group.
“Unresectable advanced or metastatic ESCC is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting,” commented Jaffer A. Ajani, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center, Houston. He was also the lead U.S. investigator for CheckMate-648 and, in a company press release, said the “two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”
Results from the trial were presented at the 2021 annual meeting of the American Society of Clinical Oncology. At that time, trial investigator Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, England, told attendees that “nivolumab plus chemotherapy and nivolumab plus ipilimumab each represent a new potential first-line standard of care for patients with advanced ESCC.”
Commenting on that presentation, Samuel J. Klempner, MD, a gastrointestinal medical oncologist at the Massachusetts General Hospital Cancer Center, Boston, noted that the “prospect of a chemo-free regimen for advanced ESCC with the well-studied combination of ipilimumab and nivolumab would represent a welcome addition to our treatment armamentarium.”
No new safety signals
Dr. Chau noted there were no new safety signals with either of the immunotherapies.
Nivolumab and/or chemotherapy were discontinued in 39% of patients and delayed in 71% of patients for an adverse reaction.
Nivolumab and/or ipilimumab were discontinued in 23% of patients and delayed in 46% of patients for an adverse reaction.
The manufacturer cautioned that immunotherapy with nivolumab with or without ipilimumab has been associated with severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, and infusion-related reactions.
A version of this article first appeared on Medscape.com.
The new approval for the drug, a programmed cell death–ligand-1 inhibitor, is for use in this patient population regardless of PD-L1 status.
The indication also specifies that nivolumab is to be used together with chemotherapy (with a fluoropyrimidine- and platinum-containing regimen) or in combination with ipilimumab (Yervoy), an immunotherapy with a different mechanism of action.
“Today’s approvals bring two first-line immunotherapy-based treatment options at once ... to newly diagnosed patients with unresectable advanced or metastatic ESCC,” commented Adam Lenkowsky, a senior vice president at Bristol-Myers Squibb, which makes both nivolumab and ipilimumab.
The approval of the new indication by the Food and Drug Administration was based on improved survival shown in the phase 3 CheckMate-648 trial, which involved nearly 1,000 patients. The trial had three arms and compared nivolumab plus chemotherapy (n = 321) and nivolumab plus ipilimumab (n = 324) with chemotherapy alone (n = 324).
The results showed improved survival with both nivolumab combinations compared with chemotherapy (fluorouracil and cisplatin) alone. Overall survival was improved both in all randomized patients (a secondary endpoint) and in patients whose tumors expressed PD-L1 (≥ 1%), the primary endpoint.
For the combination of nivolumab plus chemotherapy, median overall survival was 13.2 versus 10.7 months, compared with chemotherapy alone in all randomized patients, and 15.4 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
For the combination of nivolumab plus ipilimumab, median overall survival was 12.8 versus 10.7 months with chemotherapy alone in all randomized patients and 13.7 versus 9.1 months in patients whose tumors express PD-L1 (≥ 1%).
However, progression-free survival did not reach statistical significance in any group.
“Unresectable advanced or metastatic ESCC is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting,” commented Jaffer A. Ajani, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center, Houston. He was also the lead U.S. investigator for CheckMate-648 and, in a company press release, said the “two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”
Results from the trial were presented at the 2021 annual meeting of the American Society of Clinical Oncology. At that time, trial investigator Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, England, told attendees that “nivolumab plus chemotherapy and nivolumab plus ipilimumab each represent a new potential first-line standard of care for patients with advanced ESCC.”
Commenting on that presentation, Samuel J. Klempner, MD, a gastrointestinal medical oncologist at the Massachusetts General Hospital Cancer Center, Boston, noted that the “prospect of a chemo-free regimen for advanced ESCC with the well-studied combination of ipilimumab and nivolumab would represent a welcome addition to our treatment armamentarium.”
No new safety signals
Dr. Chau noted there were no new safety signals with either of the immunotherapies.
Nivolumab and/or chemotherapy were discontinued in 39% of patients and delayed in 71% of patients for an adverse reaction.
Nivolumab and/or ipilimumab were discontinued in 23% of patients and delayed in 46% of patients for an adverse reaction.
The manufacturer cautioned that immunotherapy with nivolumab with or without ipilimumab has been associated with severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, and infusion-related reactions.
A version of this article first appeared on Medscape.com.
Long COVID neuropsychiatric deficits greater than expected
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
AT APA 2022
New eosinophilic esophagitis severity score may guide treatment
The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.
The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.
In other eosinophilic disorders, such as asthma, there are well-prescribed treatment pathways based on the severity, said Evan Dellon, MD, MPH, professor of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.
“That is the ultimate aspiration for I-SEE – assess EoE severity, have that severity linked to certain outcomes and therefore be associated with certain treatment and monitoring recommendations, then reassess the patient severity in a standardized way, and then make additional treatment and monitoring changes if needed,” he said in an interview. “However, to get there a lot more research into the use of the tool will be needed.”
With support from the AGA, a multidisciplinary group – including adult and pediatric specialists in gastroenterology, asthma and immunology, pathology, epidemiology, and basic and translational research, as well as patient advocates – broke into teams to assess the available literature, developed consensus on the factors to be used, and developed consensus on the scoring system.
New ways have been developed over the years to assess patients’ responses to treatments and gauge their disease activity, from patient-reported outcomes to endoscopic assessment platforms and metrics using histology. But all of this information hadn’t been synthesized into a tool that clinicians would find practical to use, the expert group said in its paper describing the index.
How it works
The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.
In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.
Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.
Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.
Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.
Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.
The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.
Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.
“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
Simplifying clinical practice
Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.
“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”
Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.
“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”
He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.
“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”
This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.
The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.
This article was updated on June 7, 2022.
The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.
The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.
In other eosinophilic disorders, such as asthma, there are well-prescribed treatment pathways based on the severity, said Evan Dellon, MD, MPH, professor of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.
“That is the ultimate aspiration for I-SEE – assess EoE severity, have that severity linked to certain outcomes and therefore be associated with certain treatment and monitoring recommendations, then reassess the patient severity in a standardized way, and then make additional treatment and monitoring changes if needed,” he said in an interview. “However, to get there a lot more research into the use of the tool will be needed.”
With support from the AGA, a multidisciplinary group – including adult and pediatric specialists in gastroenterology, asthma and immunology, pathology, epidemiology, and basic and translational research, as well as patient advocates – broke into teams to assess the available literature, developed consensus on the factors to be used, and developed consensus on the scoring system.
New ways have been developed over the years to assess patients’ responses to treatments and gauge their disease activity, from patient-reported outcomes to endoscopic assessment platforms and metrics using histology. But all of this information hadn’t been synthesized into a tool that clinicians would find practical to use, the expert group said in its paper describing the index.
How it works
The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.
In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.
Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.
Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.
Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.
Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.
The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.
Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.
“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
Simplifying clinical practice
Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.
“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”
Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.
“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”
He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.
“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”
This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.
The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.
This article was updated on June 7, 2022.
The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.
The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.
In other eosinophilic disorders, such as asthma, there are well-prescribed treatment pathways based on the severity, said Evan Dellon, MD, MPH, professor of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.
“That is the ultimate aspiration for I-SEE – assess EoE severity, have that severity linked to certain outcomes and therefore be associated with certain treatment and monitoring recommendations, then reassess the patient severity in a standardized way, and then make additional treatment and monitoring changes if needed,” he said in an interview. “However, to get there a lot more research into the use of the tool will be needed.”
With support from the AGA, a multidisciplinary group – including adult and pediatric specialists in gastroenterology, asthma and immunology, pathology, epidemiology, and basic and translational research, as well as patient advocates – broke into teams to assess the available literature, developed consensus on the factors to be used, and developed consensus on the scoring system.
New ways have been developed over the years to assess patients’ responses to treatments and gauge their disease activity, from patient-reported outcomes to endoscopic assessment platforms and metrics using histology. But all of this information hadn’t been synthesized into a tool that clinicians would find practical to use, the expert group said in its paper describing the index.
How it works
The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.
In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.
Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.
Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.
Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.
Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.
The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.
Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.
“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
Simplifying clinical practice
Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.
“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”
Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.
“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”
He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.
“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”
This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.
The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.
This article was updated on June 7, 2022.
FROM GASTROENTEROLOGY
FDA expands indication for spinal muscular atrophy drug
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.
The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.
After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.
Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.
All babies were alive at 12 months without permanent ventilation.
“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.
“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
From newborns to older adults?
SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.
SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.
Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.
As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.
“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release.
“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.
A version of this article first appeared on Medscape.com.
‘Unlimited’ cancer costs: The Medicare Part D dilemma
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.
That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.
“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”
That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.
This situation is hardly unique.
Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.
In a recent perspective in the New England Journal of Medicine,
The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).
According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.
Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.
In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”
“This is ARBITRARY and INEQUITABLE,” she added.
What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.
Take the drug costs for two similar patients with breast cancer.
Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).
For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.
Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.
This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.
Another arbitrary difference: who qualifies for low-income subsidies under Part D. A single woman making the current median income, for instance, would not qualify for a Part D subsidy. If she was diagnosed with breast cancer and needed palbociclib, her cost for that drug alone would be nearly half her annual income, and that does not include premiums and other health care costs.
The high cost can mean foregoing treatment, stopping treatment early, or reducing spending on necessities such as food and housing. In fact, a recent study from Dr. Dusetzina and colleagues showed that for beneficiaries with cancer who do not receive subsidies under Part D, nearly 30% of initial prescriptions for specialty oncology drugs go unfilled.
Fortunately, that wasn’t the case for Dr. Dusetzina’s mother.
“Her cancer subtype is best treated with drugs covered under her medical benefit, and she has an out-of-pocket limit on that benefit,” she said. “That makes the financial difficulty less of a concern right now.”
But with a different subtype, it could have easily gone another way.
On Twitter, Dr. Dusetzina called for congressional action: “There is a lot going on now, but @SenateDems & @SenateGOP this needs to be fixed. #Medicare beneficiaries are counting on you to make sure that they can afford the drugs they need. We know that 1 in 3 people in #PartD don’t fill their cancer drugs. That is unacceptable.”
Dr. Dusetzina’s work is supported by the Commonwealth Fund. She reported relationships with the Institute for Clinical and Economic Review, the Laura and John Arnold Foundation, Leukemia and Lymphoma Society, National Academy for State Health Policy, and West Health Council, including grant funding/contracts and/or consulting work. She also serves as a commissioner for the Medicare Payment Advisory Commission (MedPAC).
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Double the pleasure: Stim patch delays early ejaculation: Study
A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.
Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.
Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.
The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.
Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
Common problem, limited options
Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.
The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.
“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.
Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.
Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.
Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.
The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.
To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.
The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.
In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.
Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
Potential reactions
No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.
Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.
The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.
Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.
“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”
Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.
Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.
“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”
Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.
A version of this article first appeared on Medscape.com.
A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.
Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.
Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.
The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.
Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
Common problem, limited options
Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.
The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.
“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.
Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.
Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.
Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.
The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.
To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.
The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.
In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.
Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
Potential reactions
No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.
Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.
The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.
Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.
“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”
Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.
Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.
“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”
Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.
A version of this article first appeared on Medscape.com.
A wearable patch that delivers electrical stimulation to the perineum may postpone premature ejaculation, according to research presented at the annual meeting of the American Urological Association. The disposable device appears to work by helping men contract the muscles in the pelvic floor, allowing them to postpone climax.
Among 34 men with a lifelong history of premature ejaculation, average intravaginal ejaculatory latency time – the time from vaginal penetration to ejaculation – increased from about 67 seconds at baseline to 123 seconds when they used the device.
Another 17 participants received a sham treatment – stimulation they could feel but that did not activate muscles. In this group, time to ejaculation increased from 63 seconds to 81 seconds.
The longer duration with active treatment was statistically significant (P < .0001), whereas the increase in the control group was not (P = .1653), said Ege Can Serefoglu, MD, a researcher at Biruni University, Istanbul, and editor-in-chief of the International Journal of Impotence Research.
Dr. Serefoglu is a member of the scientific advisory board for Virility Medical, a company in Hod Hasharon, Israel, that is developing the stimulator. Marketed as vPatch, the device is expected to be available in 2023, Dr. Serefoglu said. It was cleared by the Food and Drug Administration in November and has CE-mark approval in Europe, according to the company.
Common problem, limited options
Research shows that 20%-30% of men are not happy with their time to ejaculation, Dr. Serefoglu said.
The International Society for Sexual Medicine defines premature ejaculation as ejaculation which always or almost always occurs within about 1 minute of penetration, the patient is unable to delay this occurrence, and the condition causes personal distress.
“Unfortunately, in spite of its high prevalence we do not really have any satisfying treatment options,” Dr. Serefoglu said.
Topical anesthetics may be used to decrease the sensitivity of the glans penis, and selective serotonin reuptake inhibitors may help delay ejaculation. But these options have limited efficacy and low adherence, he said.
Preclinical studies have shown that injection of botulinum toxin into the bulbospongiosus muscles is associated with a dose-dependent increase in ejaculation latency in rats.
Data on ClinicalTrials.gov show that this approach also may increase ejaculation latency in men, Dr. Serefoglu said. Although investigators found no safety concerns, drugmaker Allergan made a strategic business decision to stop developing this treatment approach, according to the registration entry for the study.
The idea for vPatch came from researchers wondering if instead of paralyzing the muscles with botulinum toxin, they used electrical stimulation to cause contraction of those muscles, Dr. Serefoglu said. A smaller proof-of-concept study demonstrated the feasibility and safety of this technique.
To further assess the safety and efficacy of a transcutaneous perineal electrical stimulator for the treatment of premature ejaculation, investigators conducted the randomized, double-blind, sham-controlled trial at Rambam Medical Centre, Haifa, Israel, and Villa Donatello Clinic, Florence, Italy.
The trial included males with premature ejaculation aged 18-60 years. Their female partners measured IELT using a stopwatch during four sexual intercourse sessions before treatment, and four times on treatment, at home.
In addition to the increased time to ejaculation, perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, and interpersonal difficulty related to ejaculation all significantly improved with vPatch, the researchers found.
Of participants who received active treatment, 73.5% reported a subjective sense of improvement versus 41.2% of the control group.
Potential reactions
No serious adverse events were observed, Dr. Serefoglu reported. Potential adverse reactions include redness, discomfort, and localized pain, according to the company’s website.
Men should not use vPatch if they have been diagnosed with pelvic cancer, or if they have an implanted electronic device, diabetes with peripheral neuropathy, or perineal dermatologic diseases, irritations, or lesions. Other precautions include avoiding use of the vPatch in water or humid environments. The device has not been tested on use with a pregnant partner.
The disposable patches are meant for one-time use. “The miniaturized perineal stimulation device may become an on-demand, drug-free therapeutic option,” Dr. Serefoglu said.
Combining electrical stimulation with other treatment approaches may provide additional benefit, said Bradley Schwartz, DO, professor and chairman of urology at Southern Illinois University, Springfield, who moderated the session at the AUA meeting at which the results of the study were presented.
“You go from 1 to 2 minutes just with this device,” Dr. Schwartz said. “If you went from 2 to 3 minutes, you would essentially be tripling their pleasure or their time, which might make a significant difference.”
Serefoglu agreed that combining the stimulator with other treatment approaches such as topical anesthetics could increase patient satisfaction.
Comoderator Kelly Healy, MD, assistant professor of urology at Columbia University Medical Center, New York, highlighted a direction for future research: examining outcomes according to different types of relationships, as well as partner satisfaction.
“That is a perfect question that should also be considered in the future trials,” Dr. Serefoglu said. “This was mainly focused on the man’s satisfaction. But men are trying to delay their ejaculation to satisfy their partner.”
Dr. Serefoglu is on the scientific advisory board for Virility Medical, which sponsored the study. Dr. Healy had no disclosures. Dr. Schwartz disclosed ties to Cook Medical.
A version of this article first appeared on Medscape.com.
Two years after UCNS switch to continuous certification, major frustrations remain
Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.
Now he’s calling fraud.
After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.
“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”
That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.
It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.
Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”
In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
The changing landscape of recertification
According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.
“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.
Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.
“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”
Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.
He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.
“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
A compromise
Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.
Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.
“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.
At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.
“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”
Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”
“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”
Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”
After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.
“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
A different viewpoint
Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.
“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”
Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”
Profits over promises
Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.
“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”
Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”
According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
Proprietary tests drive revenue
According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.
“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”
NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.
Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.
While this benefits physicians, Ms. Collins added, it also reduces the bottom line.
NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”
Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.
“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”
Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.
For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
Recertification highlights a generational gap
Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.
“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.
He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”
He said the answer could depend on age.
“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”
Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.
“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”
In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.
“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”
Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.
“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.
And so, the practical value of board certification may depend most on the tenure of the person holding paper.
“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.
Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”
Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.
Now he’s calling fraud.
After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.
“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”
That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.
It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.
Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”
In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
The changing landscape of recertification
According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.
“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.
Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.
“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”
Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.
He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.
“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
A compromise
Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.
Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.
“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.
At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.
“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”
Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”
“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”
Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”
After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.
“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
A different viewpoint
Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.
“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”
Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”
Profits over promises
Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.
“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”
Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”
According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
Proprietary tests drive revenue
According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.
“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”
NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.
Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.
While this benefits physicians, Ms. Collins added, it also reduces the bottom line.
NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”
Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.
“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”
Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.
For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
Recertification highlights a generational gap
Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.
“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.
He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”
He said the answer could depend on age.
“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”
Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.
“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”
In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.
“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”
Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.
“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.
And so, the practical value of board certification may depend most on the tenure of the person holding paper.
“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.
Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”
Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.
Now he’s calling fraud.
After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.
“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”
That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.
It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.
Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”
In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
The changing landscape of recertification
According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.
“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.
Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.
“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”
Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.
He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.
“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
A compromise
Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.
Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.
“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.
At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.
“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”
Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”
“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”
Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”
After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.
“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
A different viewpoint
Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.
“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”
Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”
Profits over promises
Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.
“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”
Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”
According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
Proprietary tests drive revenue
According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.
“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”
NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.
Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.
While this benefits physicians, Ms. Collins added, it also reduces the bottom line.
NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”
Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.
“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”
Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.
For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
Recertification highlights a generational gap
Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.
“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.
He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”
He said the answer could depend on age.
“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”
Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.
“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”
In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.
“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”
Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.
“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.
And so, the practical value of board certification may depend most on the tenure of the person holding paper.
“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.
Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”
Time-restricted eating may reduce CVD risk after breast cancer
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
, a single-group feasibility study suggests.
The results show a 15% relative decline in cardiovascular risk, measured using the Framingham Risk Score, among at-risk breast cancer survivors (BCS) after only 8 weeks of following a time-restricted eating regimen, reported Amy A. Kirkham, PhD, assistant professor of kinesiology and physical education, University of Toronto, and colleagues.
“Time-restricted eating also significantly decreased visceral adipose tissue (VAT), which our team has previously found to accumulate rapidly with cardiotoxic treatment and predict later cardiac events among BCS,” the researchers add.
The findings were published online in the Journal of the American College of Cardiology: Cardiac Onco.
Physical activity is one of the main modalities for lowering cardiovascular risk, but it is not feasible for everyone because of physical limitations and other factors, noted Dr. Kirkham.
“I became interested in time-restricted eating when I came across the literature, which has really exploded in the last 5 years, showing that it can reduce the number of cardiovascular risk factors,” she said in an interview.
“However, most of these populations studied have had cardiometabolic conditions, like obesity, type 2 diabetes, prediabetes, and metabolic syndrome, and no one has looked at this” in either the population specifically at high risk for cardiovascular disease or in patients with overt cardiovascular disease, she said.
This approach is easy for patients to follow and is much simpler than many of the other dietary patterns, noted Dr. Kirkham. “It simply consists of having a start time or end time to your eating, so it is easy to prescribe,” she said. “You can see how that is much easier for a doctor to explain to a patient than trying to explain how to meet the physical activity guidelines each week.”
“This particular study definitely shows that time-restricted eating can decrease the calorie intake, and I think by decreasing the calorie intake you definitely would improve the body weight, which has numerous benefits irrespective of how we arrive at the end goal which is including the cardiovascular risk factors,” said Ajay Vallakati, MBBS, physician and clinical assistant professor of internal medicine, the Ohio State University, Columbus, commenting on the study.
“I think time-restricted eating is a tool we should look at, and a bigger study would help us to recommend this for our patients,” Dr. Vallakati told this news organization.
The study involved 22 participants. Mean age was 66 years. Mean body mass index was 31 ± 5 kg/m². In the cohort, 91% of participants were taking aromatase inhibitors and tamoxifen at the time of the study, and 50% underwent left-sided radiation.
The study group included breast cancer survivors who had risk factors for cardiovascular disease mortality, including completion of cardiotoxic therapy, like anthracyclines, within 1-6 years, obesity/overweight, and older age, defined as 60 years of age or older.
Participants were allowed to eat freely between 12 PM and 8 PM on weekdays and any time during weekends. Outside of the allotted hours, they could only drink black coffee, water, or black tea for the 8-week study period. They were not under any other physical activity or dietary restrictions.
All were provided with behavioral support, such as check-in phone calls with the research team at 1-, 3-, and 6-week follow-up and pre-interventional calls from a registered dietitian. During weekdays, they also received automated text messages twice a day asking what time they started and stopped eating.
Irritability and headaches were among the transient, minor symptoms reported, the researchers say. The study group responded to nearly all of the text messages that they received from the researchers. The participants also followed through with the fast for a median 98% of the prescribed days by fasting for 16 or more hours.
The results showed that after 8 weeks, median Framingham cardiovascular risk declined from 10.9% to 8.6%, a 15% relative reduction (P = .037). Modifiable aspects of Framingham, such as systolic blood pressure, total cholesterol, and high-density lipoprotein, remained relatively consistent overall, however, suggesting variation between individuals in the etiology of the risk decline.
Caloric intake fell by a median of 450 kcal, representing a relative reduction of about 22% (P < .001), they note.
The findings also showed a decline in median derived whole-body fat mass (–0.9 kg; P = .046), body mass (–1.0 kg; P = .025), and mean MRI-derived VAT (–5%; P = .009).
Other data showed that the average BMI remained the same (P = .10).
At the beginning of the study, 68% of the cohort was considered cardiometabolically unhealthy, given the benchmarks for pharmacologic preventive therapy of cardiovascular risk or metabolic syndrome based on Canadian Cardiovascular Society recommendations.
Notably, 53% of the cohort was no longer classified as meeting the criteria for metabolic syndrome or for the therapeutic treatment of cardiovascular risk after the intervention.
The study’s limitations include its short duration, selection bias, and that it did not involve a control group, the researchers acknowledge.
“Randomized controlled trials are needed to confirm these findings and to evaluate the health benefits, including potential health care cost savings and safety of longer-term time-restricted eating,” the researchers conclude.
Dr. Vallakati and Dr. Kirkham report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY: CARDIAC ONCO
Mother’s distress disrupts fetal brain development
Babies of mothers who experience significant psychological distress during pregnancy showed evidence of altered brain development in utero and reduced cognitive outcomes at 18 months, based on data from a pair of studies including approximately 300 women.
In a longitudinal study published in JAMA Network Open, Yao Wu, PhD, of Children’s National Hospital, Washington, and colleagues recruited 97 healthy mother-infant dyads between January 2016 and October 2020 at a single center. Of these, 87 underwent two fetal brain imaging studies each, and 10 completed the first MRI visit, for a total of 184 fetal MRIs.
Neurodevelopment and social-emotional development for infants at 18 months of age was measured using the Bayley Scales of Infant and Toddler Development and Infant-Toddler Social and Emotional Assessment. The mean age of the mothers was 35 years; maternal distress was assessed between 24 and 40 weeks’ gestation using validated self-report questionnaires. Parenting stress was assessed at the 18-month infant testing using the Parenting Stress Index-Short Form.
Overall, prenatal maternal stress was negatively associated with infant cognitive performance (P = .01) at 18 months, mediated by fetal left hippocampal volume.
In addition, increased fetal cortical local gyrification index and sulcal depth measured during reported times of prenatal maternal distress were associated with significantly poorer social-emotional scores and competence scores at age 18 months. The beta coefficients for local gyrification index and sulcal depth were –54.62 and –14.22, respectively, for social-emotional and competence scores, –24.01 and –7.53, respectively; P values were P < .001, P < .002, P = .003, P < .001, respectively.
“Increased cortical gyrification has been suggested in children with dyslexia and autism, and sulcal depth has been associated with the severity of impaired performance on working memory and executive function in adults with schizophrenia,” the researchers wrote in their discussion of the findings.
The current study “extends our previous findings and suggests a critical role for disturbances in emerging fetal cerebral cortical folding development in mediating the association between prenatal maternal distress and neurodevelopmental problems that later manifest in infancy,” they explained.
The researchers also found that prenatal maternal anxiety, stress, and depression were positively associated with all measures of parenting stress at the 18-month testing visit.
The study findings were limited by several factors including the use of self-reports for both maternal distress and infant social-emotional assessment, despite the use of validated questionnaires, and the fact that assessment of maternal distress at specific times may not reflect the entire pregnancy, the researchers noted. Other potential limitations included the inability to use some MRI data because of fetal movement and the homogenous population of relatively highly educated women with access to health care that may not reflect other areas, they said.
“Identifying early brain developmental biomarkers may help improve the identification of infants at risk for later neurodevelopmental impairment who might benefit from early targeted interventions,” the researchers concluded.
Technology enhances health and disease models
The effect of the prenatal period on future well-being is recognized, but the current study makes “substantial contributions to prenatal programming science, with implications for ways to transform the prenatal care ecosystem for two-generation impact,” Catherine Monk, PhD, and Cristina R. Fernández, MD, both of Columbia University, New York, wrote in an accompanying editorial.
The developmental origins of health and disease (DOHaD) conceptual model introduced by Dr. David Barker in 1995 were later applied to show that maternal stress, depression, and anxiety affected child prenatal and future development, they said. However, the current study uses cutting-edge neuroscience to directly assess developing fetal brains. The finding of reduced cognitive functioning at 18 months associated with maternal stress is consistent with other findings, they noted.
“Finding an association between maternal prenatal stress and infant cognitive outcomes in the setting of what may be modest stress relative to that of a low-resourced or historically marginalized sample underscores the importance of this research; presumably, with higher stress, and greater social determinants of health burden, the effect sizes would be even greater and of greater concern,” they said.
However, studies such as the current one “have the potential to transform the prenatal and postpartum care ecosystems,” by encouraging a whole-person approach to the care of pregnant women, including attention to mental well-being and quality of life, they emphasized.
COVID-19 stress considerations
In a separate study published in Communications Medicine, Yuan-Chiao Lu, MD, also of Children’s National Hospital in Washington, and colleagues found a similar effect of maternal stress on fetal brain development.
The researchers imaged the brains of fetuses before and during the COVID-19 pandemic and interviewed mothers about any distress they experienced during pregnancy.
The study population included 65 women with known COVID-19 exposures who underwent 92 fetal MRIs and 137 prepandemic controls who underwent 182 fetal MRIs. Maternal distress was measured via the Spielberger State Anxiety Inventory, Spielberger Trait Anxiety Inventory, Perceived Stress Scale, and Edinburgh Postnatal Depression Scale.
Overall, scores on measures of stress and depression were significantly higher for women in the pandemic group compared with controls. Of the 173 women for whom maternal distress measures were available, 28% of the prepandemic group and 52% of the pandemic group met criteria for elevated maternal psychological distress, defined as above the threshold for distress on any one of the four measures.
After the researchers controlled for maternal distress, MRI data showed decreases in fetal white matter and in hippocampal and cerebellar volumes in fetuses in the pandemic group compared with controls.
Other signs of impaired brain development were similar to those seen in the JAMA Network Open study, including decreased cortical surface area and local gyrification index, as well as reduced sulcal depth in multiple brain lobes, indicating delayed cerebral cortical gyrification.
The second study was limited by a lack of data on other lifestyle changes during the pandemic that might influence maternal health and fetal development, the researchers noted. Other limitations were the possible lack of generalizability to a range of racial and ethnic populations and geographic areas outside of Washington, and the inability to control for unknown COVID-19 exposures or subclinical infections in controls, they said.
However, the results support findings from previous studies, and provide a unique opportunity to study the effect of prenatal stress on early development, as well as a chance to implement “novel and timely interventions,” the researchers wrote.
“Monitoring the COVID generation of infants for long-term cognitive and health outcomes after birth is warranted and currently underway,” and continued research may inform preventive strategies for pregnant women experiencing multiple stressors beyond the pandemic, they concluded.
Interpret pandemic effect with caution
“Research studies, as well as our own daily experiences, have made it abundantly clear that stress is on the rise as a consequence of the COVID-19 pandemic,” said editorial author Dr. Monk, who commented on the second study in an interview. “This is an important public health question: Early identification of pandemic effects on child development can help garner the necessary resources to intervene early, dramatically increasing the likelihood of improving that child’s developmental trajectory,” she said.
“The pandemic is an unprecedented experience that has widespread impact on people’s lives, how could it not also alter gestational biology and the developing brain? That being said, we need to be cautious in that we do not yet know the functional implications of these brain changes for longer-term development,” Dr. Monk said. “Also, we do not know what aspects of women’s pandemic-affected lives had an influence on fetal brain development. The authors found higher stress in pandemic versus nonpandemic women, but not evidence that distress was the mediating variable relating pregnancy during the pandemic to altered brain development,” she explained.
The take-home message for clinicians is to “provide your patients with realistic avenues for neurodevelopmental assessments of their children if they, or you, have concerns,” Dr. Monk said. “However, do not prejudge ‘pandemic babies,’ as not all children will be affected by these potential pandemic effects,” she emphasized. “It is possible to misjudge normal variation in children’s development and unnecessarily raise parents’ anxiety levels. Importantly, this period of brain plasticity means any needed intervention likely can have a big, ameliorating impact,” she added.
“We need follow-up studies looking at pandemic effects on prenatal and postnatal development and what factors protect the fetus and birthing person from the negative influences,” she said.
The JAMA study was supported by the National Institutes of Health and the A. James & Alice B. Clark Foundation. The study in Communications Medicine was supported by the National Institutes of Health, the Intellectual and Developmental Disabilities Research Center, and the A. James & Alice B. Clark Foundation. None of the researchers in either study disclosed conflicts of interest. Dr. Monk disclosed grants from the National Institutes of Health, the Bezos Family Foundation, and the Robin Hood Foundation outside the submitted work.
Babies of mothers who experience significant psychological distress during pregnancy showed evidence of altered brain development in utero and reduced cognitive outcomes at 18 months, based on data from a pair of studies including approximately 300 women.
In a longitudinal study published in JAMA Network Open, Yao Wu, PhD, of Children’s National Hospital, Washington, and colleagues recruited 97 healthy mother-infant dyads between January 2016 and October 2020 at a single center. Of these, 87 underwent two fetal brain imaging studies each, and 10 completed the first MRI visit, for a total of 184 fetal MRIs.
Neurodevelopment and social-emotional development for infants at 18 months of age was measured using the Bayley Scales of Infant and Toddler Development and Infant-Toddler Social and Emotional Assessment. The mean age of the mothers was 35 years; maternal distress was assessed between 24 and 40 weeks’ gestation using validated self-report questionnaires. Parenting stress was assessed at the 18-month infant testing using the Parenting Stress Index-Short Form.
Overall, prenatal maternal stress was negatively associated with infant cognitive performance (P = .01) at 18 months, mediated by fetal left hippocampal volume.
In addition, increased fetal cortical local gyrification index and sulcal depth measured during reported times of prenatal maternal distress were associated with significantly poorer social-emotional scores and competence scores at age 18 months. The beta coefficients for local gyrification index and sulcal depth were –54.62 and –14.22, respectively, for social-emotional and competence scores, –24.01 and –7.53, respectively; P values were P < .001, P < .002, P = .003, P < .001, respectively.
“Increased cortical gyrification has been suggested in children with dyslexia and autism, and sulcal depth has been associated with the severity of impaired performance on working memory and executive function in adults with schizophrenia,” the researchers wrote in their discussion of the findings.
The current study “extends our previous findings and suggests a critical role for disturbances in emerging fetal cerebral cortical folding development in mediating the association between prenatal maternal distress and neurodevelopmental problems that later manifest in infancy,” they explained.
The researchers also found that prenatal maternal anxiety, stress, and depression were positively associated with all measures of parenting stress at the 18-month testing visit.
The study findings were limited by several factors including the use of self-reports for both maternal distress and infant social-emotional assessment, despite the use of validated questionnaires, and the fact that assessment of maternal distress at specific times may not reflect the entire pregnancy, the researchers noted. Other potential limitations included the inability to use some MRI data because of fetal movement and the homogenous population of relatively highly educated women with access to health care that may not reflect other areas, they said.
“Identifying early brain developmental biomarkers may help improve the identification of infants at risk for later neurodevelopmental impairment who might benefit from early targeted interventions,” the researchers concluded.
Technology enhances health and disease models
The effect of the prenatal period on future well-being is recognized, but the current study makes “substantial contributions to prenatal programming science, with implications for ways to transform the prenatal care ecosystem for two-generation impact,” Catherine Monk, PhD, and Cristina R. Fernández, MD, both of Columbia University, New York, wrote in an accompanying editorial.
The developmental origins of health and disease (DOHaD) conceptual model introduced by Dr. David Barker in 1995 were later applied to show that maternal stress, depression, and anxiety affected child prenatal and future development, they said. However, the current study uses cutting-edge neuroscience to directly assess developing fetal brains. The finding of reduced cognitive functioning at 18 months associated with maternal stress is consistent with other findings, they noted.
“Finding an association between maternal prenatal stress and infant cognitive outcomes in the setting of what may be modest stress relative to that of a low-resourced or historically marginalized sample underscores the importance of this research; presumably, with higher stress, and greater social determinants of health burden, the effect sizes would be even greater and of greater concern,” they said.
However, studies such as the current one “have the potential to transform the prenatal and postpartum care ecosystems,” by encouraging a whole-person approach to the care of pregnant women, including attention to mental well-being and quality of life, they emphasized.
COVID-19 stress considerations
In a separate study published in Communications Medicine, Yuan-Chiao Lu, MD, also of Children’s National Hospital in Washington, and colleagues found a similar effect of maternal stress on fetal brain development.
The researchers imaged the brains of fetuses before and during the COVID-19 pandemic and interviewed mothers about any distress they experienced during pregnancy.
The study population included 65 women with known COVID-19 exposures who underwent 92 fetal MRIs and 137 prepandemic controls who underwent 182 fetal MRIs. Maternal distress was measured via the Spielberger State Anxiety Inventory, Spielberger Trait Anxiety Inventory, Perceived Stress Scale, and Edinburgh Postnatal Depression Scale.
Overall, scores on measures of stress and depression were significantly higher for women in the pandemic group compared with controls. Of the 173 women for whom maternal distress measures were available, 28% of the prepandemic group and 52% of the pandemic group met criteria for elevated maternal psychological distress, defined as above the threshold for distress on any one of the four measures.
After the researchers controlled for maternal distress, MRI data showed decreases in fetal white matter and in hippocampal and cerebellar volumes in fetuses in the pandemic group compared with controls.
Other signs of impaired brain development were similar to those seen in the JAMA Network Open study, including decreased cortical surface area and local gyrification index, as well as reduced sulcal depth in multiple brain lobes, indicating delayed cerebral cortical gyrification.
The second study was limited by a lack of data on other lifestyle changes during the pandemic that might influence maternal health and fetal development, the researchers noted. Other limitations were the possible lack of generalizability to a range of racial and ethnic populations and geographic areas outside of Washington, and the inability to control for unknown COVID-19 exposures or subclinical infections in controls, they said.
However, the results support findings from previous studies, and provide a unique opportunity to study the effect of prenatal stress on early development, as well as a chance to implement “novel and timely interventions,” the researchers wrote.
“Monitoring the COVID generation of infants for long-term cognitive and health outcomes after birth is warranted and currently underway,” and continued research may inform preventive strategies for pregnant women experiencing multiple stressors beyond the pandemic, they concluded.
Interpret pandemic effect with caution
“Research studies, as well as our own daily experiences, have made it abundantly clear that stress is on the rise as a consequence of the COVID-19 pandemic,” said editorial author Dr. Monk, who commented on the second study in an interview. “This is an important public health question: Early identification of pandemic effects on child development can help garner the necessary resources to intervene early, dramatically increasing the likelihood of improving that child’s developmental trajectory,” she said.
“The pandemic is an unprecedented experience that has widespread impact on people’s lives, how could it not also alter gestational biology and the developing brain? That being said, we need to be cautious in that we do not yet know the functional implications of these brain changes for longer-term development,” Dr. Monk said. “Also, we do not know what aspects of women’s pandemic-affected lives had an influence on fetal brain development. The authors found higher stress in pandemic versus nonpandemic women, but not evidence that distress was the mediating variable relating pregnancy during the pandemic to altered brain development,” she explained.
The take-home message for clinicians is to “provide your patients with realistic avenues for neurodevelopmental assessments of their children if they, or you, have concerns,” Dr. Monk said. “However, do not prejudge ‘pandemic babies,’ as not all children will be affected by these potential pandemic effects,” she emphasized. “It is possible to misjudge normal variation in children’s development and unnecessarily raise parents’ anxiety levels. Importantly, this period of brain plasticity means any needed intervention likely can have a big, ameliorating impact,” she added.
“We need follow-up studies looking at pandemic effects on prenatal and postnatal development and what factors protect the fetus and birthing person from the negative influences,” she said.
The JAMA study was supported by the National Institutes of Health and the A. James & Alice B. Clark Foundation. The study in Communications Medicine was supported by the National Institutes of Health, the Intellectual and Developmental Disabilities Research Center, and the A. James & Alice B. Clark Foundation. None of the researchers in either study disclosed conflicts of interest. Dr. Monk disclosed grants from the National Institutes of Health, the Bezos Family Foundation, and the Robin Hood Foundation outside the submitted work.
Babies of mothers who experience significant psychological distress during pregnancy showed evidence of altered brain development in utero and reduced cognitive outcomes at 18 months, based on data from a pair of studies including approximately 300 women.
In a longitudinal study published in JAMA Network Open, Yao Wu, PhD, of Children’s National Hospital, Washington, and colleagues recruited 97 healthy mother-infant dyads between January 2016 and October 2020 at a single center. Of these, 87 underwent two fetal brain imaging studies each, and 10 completed the first MRI visit, for a total of 184 fetal MRIs.
Neurodevelopment and social-emotional development for infants at 18 months of age was measured using the Bayley Scales of Infant and Toddler Development and Infant-Toddler Social and Emotional Assessment. The mean age of the mothers was 35 years; maternal distress was assessed between 24 and 40 weeks’ gestation using validated self-report questionnaires. Parenting stress was assessed at the 18-month infant testing using the Parenting Stress Index-Short Form.
Overall, prenatal maternal stress was negatively associated with infant cognitive performance (P = .01) at 18 months, mediated by fetal left hippocampal volume.
In addition, increased fetal cortical local gyrification index and sulcal depth measured during reported times of prenatal maternal distress were associated with significantly poorer social-emotional scores and competence scores at age 18 months. The beta coefficients for local gyrification index and sulcal depth were –54.62 and –14.22, respectively, for social-emotional and competence scores, –24.01 and –7.53, respectively; P values were P < .001, P < .002, P = .003, P < .001, respectively.
“Increased cortical gyrification has been suggested in children with dyslexia and autism, and sulcal depth has been associated with the severity of impaired performance on working memory and executive function in adults with schizophrenia,” the researchers wrote in their discussion of the findings.
The current study “extends our previous findings and suggests a critical role for disturbances in emerging fetal cerebral cortical folding development in mediating the association between prenatal maternal distress and neurodevelopmental problems that later manifest in infancy,” they explained.
The researchers also found that prenatal maternal anxiety, stress, and depression were positively associated with all measures of parenting stress at the 18-month testing visit.
The study findings were limited by several factors including the use of self-reports for both maternal distress and infant social-emotional assessment, despite the use of validated questionnaires, and the fact that assessment of maternal distress at specific times may not reflect the entire pregnancy, the researchers noted. Other potential limitations included the inability to use some MRI data because of fetal movement and the homogenous population of relatively highly educated women with access to health care that may not reflect other areas, they said.
“Identifying early brain developmental biomarkers may help improve the identification of infants at risk for later neurodevelopmental impairment who might benefit from early targeted interventions,” the researchers concluded.
Technology enhances health and disease models
The effect of the prenatal period on future well-being is recognized, but the current study makes “substantial contributions to prenatal programming science, with implications for ways to transform the prenatal care ecosystem for two-generation impact,” Catherine Monk, PhD, and Cristina R. Fernández, MD, both of Columbia University, New York, wrote in an accompanying editorial.
The developmental origins of health and disease (DOHaD) conceptual model introduced by Dr. David Barker in 1995 were later applied to show that maternal stress, depression, and anxiety affected child prenatal and future development, they said. However, the current study uses cutting-edge neuroscience to directly assess developing fetal brains. The finding of reduced cognitive functioning at 18 months associated with maternal stress is consistent with other findings, they noted.
“Finding an association between maternal prenatal stress and infant cognitive outcomes in the setting of what may be modest stress relative to that of a low-resourced or historically marginalized sample underscores the importance of this research; presumably, with higher stress, and greater social determinants of health burden, the effect sizes would be even greater and of greater concern,” they said.
However, studies such as the current one “have the potential to transform the prenatal and postpartum care ecosystems,” by encouraging a whole-person approach to the care of pregnant women, including attention to mental well-being and quality of life, they emphasized.
COVID-19 stress considerations
In a separate study published in Communications Medicine, Yuan-Chiao Lu, MD, also of Children’s National Hospital in Washington, and colleagues found a similar effect of maternal stress on fetal brain development.
The researchers imaged the brains of fetuses before and during the COVID-19 pandemic and interviewed mothers about any distress they experienced during pregnancy.
The study population included 65 women with known COVID-19 exposures who underwent 92 fetal MRIs and 137 prepandemic controls who underwent 182 fetal MRIs. Maternal distress was measured via the Spielberger State Anxiety Inventory, Spielberger Trait Anxiety Inventory, Perceived Stress Scale, and Edinburgh Postnatal Depression Scale.
Overall, scores on measures of stress and depression were significantly higher for women in the pandemic group compared with controls. Of the 173 women for whom maternal distress measures were available, 28% of the prepandemic group and 52% of the pandemic group met criteria for elevated maternal psychological distress, defined as above the threshold for distress on any one of the four measures.
After the researchers controlled for maternal distress, MRI data showed decreases in fetal white matter and in hippocampal and cerebellar volumes in fetuses in the pandemic group compared with controls.
Other signs of impaired brain development were similar to those seen in the JAMA Network Open study, including decreased cortical surface area and local gyrification index, as well as reduced sulcal depth in multiple brain lobes, indicating delayed cerebral cortical gyrification.
The second study was limited by a lack of data on other lifestyle changes during the pandemic that might influence maternal health and fetal development, the researchers noted. Other limitations were the possible lack of generalizability to a range of racial and ethnic populations and geographic areas outside of Washington, and the inability to control for unknown COVID-19 exposures or subclinical infections in controls, they said.
However, the results support findings from previous studies, and provide a unique opportunity to study the effect of prenatal stress on early development, as well as a chance to implement “novel and timely interventions,” the researchers wrote.
“Monitoring the COVID generation of infants for long-term cognitive and health outcomes after birth is warranted and currently underway,” and continued research may inform preventive strategies for pregnant women experiencing multiple stressors beyond the pandemic, they concluded.
Interpret pandemic effect with caution
“Research studies, as well as our own daily experiences, have made it abundantly clear that stress is on the rise as a consequence of the COVID-19 pandemic,” said editorial author Dr. Monk, who commented on the second study in an interview. “This is an important public health question: Early identification of pandemic effects on child development can help garner the necessary resources to intervene early, dramatically increasing the likelihood of improving that child’s developmental trajectory,” she said.
“The pandemic is an unprecedented experience that has widespread impact on people’s lives, how could it not also alter gestational biology and the developing brain? That being said, we need to be cautious in that we do not yet know the functional implications of these brain changes for longer-term development,” Dr. Monk said. “Also, we do not know what aspects of women’s pandemic-affected lives had an influence on fetal brain development. The authors found higher stress in pandemic versus nonpandemic women, but not evidence that distress was the mediating variable relating pregnancy during the pandemic to altered brain development,” she explained.
The take-home message for clinicians is to “provide your patients with realistic avenues for neurodevelopmental assessments of their children if they, or you, have concerns,” Dr. Monk said. “However, do not prejudge ‘pandemic babies,’ as not all children will be affected by these potential pandemic effects,” she emphasized. “It is possible to misjudge normal variation in children’s development and unnecessarily raise parents’ anxiety levels. Importantly, this period of brain plasticity means any needed intervention likely can have a big, ameliorating impact,” she added.
“We need follow-up studies looking at pandemic effects on prenatal and postnatal development and what factors protect the fetus and birthing person from the negative influences,” she said.
The JAMA study was supported by the National Institutes of Health and the A. James & Alice B. Clark Foundation. The study in Communications Medicine was supported by the National Institutes of Health, the Intellectual and Developmental Disabilities Research Center, and the A. James & Alice B. Clark Foundation. None of the researchers in either study disclosed conflicts of interest. Dr. Monk disclosed grants from the National Institutes of Health, the Bezos Family Foundation, and the Robin Hood Foundation outside the submitted work.
FROM JAMA NETWORK OPEN AND COMMUNICATIONS MEDICINE