Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.

The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.

“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.

Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”

Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.

“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.

“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
 

Risks for higher BMI substantially greater in the youngest adults

The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.

Changes in BMI were assessed at 1 year, 5 years, and 10 years.

At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).

Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.

They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).

Online risk calculator and YouTube video help explain findings 

While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.

For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.

The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.

“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.

From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.

They have also posted a video on YouTube to help explain their findings.
 

COVID and obesity pandemics collide

Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.

“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.

“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”

The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.

The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.

“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.

Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”

Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.

“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.

“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
 

Risks for higher BMI substantially greater in the youngest adults

The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.

Changes in BMI were assessed at 1 year, 5 years, and 10 years.

At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).

Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.

They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).

Online risk calculator and YouTube video help explain findings 

While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.

For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.

The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.

“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.

From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.

They have also posted a video on YouTube to help explain their findings.
 

COVID and obesity pandemics collide

Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.

“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.

“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”

The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.

The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.

“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.

Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”

Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.

“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.

“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
 

Risks for higher BMI substantially greater in the youngest adults

The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.

Changes in BMI were assessed at 1 year, 5 years, and 10 years.

At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).

Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.

They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).

Online risk calculator and YouTube video help explain findings 

While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.

For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.

The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.

“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.

From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.

They have also posted a video on YouTube to help explain their findings.
 

COVID and obesity pandemics collide

Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.

“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.

“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”

The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

The first transdermal contraceptive patch was approved by the US Food and Drug Administration (FDA) in 2001.¹ A 2018 survey revealed that 5% of women in the United States between the ages of 15 and 49 years reported the use of a short-acting hormonal contraceptive method (ie, vaginal ring, transdermal patch, injectable) within the past month, with just 0.3% reporting the use of a transdermal patch.² Transdermal contraceptive patches are an effective form of birth control that may be a convenient option for patients who do not want to take a daily oral contraceptive pill but want similar efficacy and tolerability. Typical failure rates of patches are similar to that of combined oral contraceptives (COCs).^1,3

While transdermal hormone delivery results in less peaks and troughs of estrogen compared with COCs, the total estrogen exposure is higher than with COCs; therefore, the risk for venous thromboembolism (VTE) with previously available patches is about twice as high.¹ Twirla (Agile), an ethinyl estradiol (EE)/levonorgestrel (LNG) patch, delivers a low and consistent daily dose of hormones over 3 patches replaced once weekly, with no patch on the fourth week.³ Twirla contains 120 μg/day LNG and 30 μg/day EE. OrthoEvra, FDA approved in 2001 as mentioned, contains 150 μg/day norelgestromin and 35 μg/day EE.¹ A reduction of the EE dose in COCs has been associated with lower risk for VTE.⁴

The addition of Twirla to the market offers another contraceptive option for patients who opt for a weekly, self-administered method.

How much lower is the VTE risk?

OBG Management: Can you define what is the reduction in VTE risk for the EE dose in Twirla versus Ortho Evra (a norelgestromin/EE patch) and similar contraceptive patches already available?

Barbara Levy, MD: The reality is we can’t designate a reduction of risk, except, in general, when the dose of ethinyl estradiol is lower, we think that the VTE risk is lower. There has not been a head-to-head comparison in a large enough population to be able to say that the risk is reduced by a certain factor. We just look at the overall exposure to estrogen and say, “In general, for VTE risk, a lower dose is a better thing for women.”

That being said, look at birth control pills, like COCs. We don’t have actual numbers to say that a 30-μg pill is this much less risky than a 35-μg pill. We just put it into a hierarchy, and that’s what we can do with the patch. We can say that, in general, lower is better for VTE risk, but no one can provide absolute numbers.

Continue to: Efficacy...

Efficacy

OBG Management: What is Twirla’s efficacy in preventing pregnancy, and how does this compare to previous patches and other types of hormonal birth control?

Dr. Levy: You have to look at the pivotal trials and look at what the efficacy was in a trial setting. In the real-world setting, the effectiveness is never quite as good as it is in a clinical trial. I think the bottom line for all of us is that combined oral contraception, meaning estrogen with progestin, is equivalently effective across the different options that are available for women. Efficacy really isn’t the factor to use to distinguish which one I’m going to pick. It is about the patient’s convenience and many other factors. But in terms of its clinical effectiveness in preventing pregnancy, from a very practical standpoint, I think we consider them all the same.

Considering route of administration

OBG Management: Are there benefits associated with transdermal birth control vs other contraceptive options, and are women interested in transdermal contraception?

Dr. Levy: I think there’s always a benefit in having lots of choices. And for some women, being able to put a patch on once a week is much more convenient, easier to remember, and delivers a very consistent dose of hormone absorbed through the skin, which is different than taking a pill in the morning when your levels go up quickly then diminish over the day. The hormones are higher at a certain time, and then they drop off, so there might be some advantages for people who are very sensitive to swings in hormonal levels. There’s also a convenience factor, where for some people they will choose that. Other people might really dislike having a relatively large patch on their skin somewhere, or they may have skin sensitivity to the adhesive. Overall, I always think that having more options is better and individual girls/women will choose what works best for them.

Counseling tips

OBG Management: What are the instructions for patients to effectively use Twirla, and how should they be counseled regarding the expectations for their menstrual cycle?

Dr. Levy: Like other patches that are available on the market, these are a once-a-week patch. The patch should be placed on clean, dry skin. No lotions, perfumes, or anything on the skin because you really want them to stick for the whole week, and it’s not going to stick if there’s anything oily on the skin. The first patch is placed on day 1 of a menstrual cycle, the first day of bleeding, and then changed weekly for 3 weeks. Then there’s a 7-day patch-free time in which one would expect to have a period.

In general, breakthrough bleeding was not a significant problem with the patch, but some women will have some irregular spotting and bleeding with any sort of hormonal treatment; some women may have no periods at all. In other words, the estrogen dose and progestin may be of a balance that allows the patient not to have periods. But, in general, most of the women in the trial had regular light menstrual flow during the week when their patch was not on.⁵

Continue to: Pricing...

Pricing

OBG Management: Are you aware of the current payment options for Twirla? Is it covered by any insurance plans right now?

Dr. Levy: That’s a tricky question. Insurance plans through Obamacare, the Affordable Care Act, are required to cover every form of contraception. That means they must cover a patch. It doesn’t mean that they have to cover this patch. And because there are generics available of the other patch formulation, it is likely that this would be a higher tier, meaning that there may be a higher copay for someone who wanted to use Twirla versus one of the generic patches.

I can’t say that that’s universally the case, but my experience with most of the health insurance plans is that they tend to put barriers in the way for any of us to prescribe, and for women to use, brand-name products. So Twirla is new on the market; it’s a brand-name product. It may work much better for some people; and in those cases, the health care provider might have to send a letter to the insurance company saying why this one is medically necessary for a patient. There probably will be some hoops to go through for coverage without a copay. I think coverage will be there, but there may be a substantial copay because of the tier level.

OBG Management: Do you think that there would be a challenge for someone trying to get a prescription for a patient saying that there is a need because it is a lower dose of estrogen?

Dr. Levy: I don’t think that the payer is going to buy that argument unless the requirement is to use a patch. If the patient, for example, has some sort of gastrointestinal disease where they don’t absorb things well, so pills don’t work well, we might get to the place where they have to have a patch. If the patient has a lot of breast tenderness or has symptoms on the generic patch that delivers a higher level of estrogen, then we would have to document those symptoms to say, “She’s not tolerating this one and, therefore, we need to go to that one.” So, I think as prescribers we would have to justify not only the lower dose but also the form.

As a clinician, I would always like to put somebody on the lower dose. We do think lower is better, but we have to be sensitive to the costs of all of these things too. I’m very sensitive to my patients’ out-of-pocket costs because, in the end, if the costs are a lot of money or she can only afford one month at a time, then she may miss a window where she may not have the money to buy next month’s supply when it’s due, and get pregnant. We have to balance all of those things as we’re thinking through the best option for an individual.

We have more to learn

OBG Management: Is there anything else you would like to add?

Dr. Levy: I think it’s always exciting when we have new products available, and there’s a lot more we’ll learn as Twirla comes into commercial use and millions instead of thousands of people are using it. Overall, I think it’s fantastic that there’s ongoing research and that there are new products out there. And kudos to the company for doing the research and for getting approval, and I’m looking forward to learning more about it.
 

The first transdermal contraceptive patch was approved by the US Food and Drug Administration (FDA) in 2001.¹ A 2018 survey revealed that 5% of women in the United States between the ages of 15 and 49 years reported the use of a short-acting hormonal contraceptive method (ie, vaginal ring, transdermal patch, injectable) within the past month, with just 0.3% reporting the use of a transdermal patch.² Transdermal contraceptive patches are an effective form of birth control that may be a convenient option for patients who do not want to take a daily oral contraceptive pill but want similar efficacy and tolerability. Typical failure rates of patches are similar to that of combined oral contraceptives (COCs).^1,3

While transdermal hormone delivery results in less peaks and troughs of estrogen compared with COCs, the total estrogen exposure is higher than with COCs; therefore, the risk for venous thromboembolism (VTE) with previously available patches is about twice as high.¹ Twirla (Agile), an ethinyl estradiol (EE)/levonorgestrel (LNG) patch, delivers a low and consistent daily dose of hormones over 3 patches replaced once weekly, with no patch on the fourth week.³ Twirla contains 120 μg/day LNG and 30 μg/day EE. OrthoEvra, FDA approved in 2001 as mentioned, contains 150 μg/day norelgestromin and 35 μg/day EE.¹ A reduction of the EE dose in COCs has been associated with lower risk for VTE.⁴

The addition of Twirla to the market offers another contraceptive option for patients who opt for a weekly, self-administered method.

How much lower is the VTE risk?

OBG Management: Can you define what is the reduction in VTE risk for the EE dose in Twirla versus Ortho Evra (a norelgestromin/EE patch) and similar contraceptive patches already available?

Barbara Levy, MD: The reality is we can’t designate a reduction of risk, except, in general, when the dose of ethinyl estradiol is lower, we think that the VTE risk is lower. There has not been a head-to-head comparison in a large enough population to be able to say that the risk is reduced by a certain factor. We just look at the overall exposure to estrogen and say, “In general, for VTE risk, a lower dose is a better thing for women.”

That being said, look at birth control pills, like COCs. We don’t have actual numbers to say that a 30-μg pill is this much less risky than a 35-μg pill. We just put it into a hierarchy, and that’s what we can do with the patch. We can say that, in general, lower is better for VTE risk, but no one can provide absolute numbers.

Continue to: Efficacy...

Efficacy

OBG Management: What is Twirla’s efficacy in preventing pregnancy, and how does this compare to previous patches and other types of hormonal birth control?

Dr. Levy: You have to look at the pivotal trials and look at what the efficacy was in a trial setting. In the real-world setting, the effectiveness is never quite as good as it is in a clinical trial. I think the bottom line for all of us is that combined oral contraception, meaning estrogen with progestin, is equivalently effective across the different options that are available for women. Efficacy really isn’t the factor to use to distinguish which one I’m going to pick. It is about the patient’s convenience and many other factors. But in terms of its clinical effectiveness in preventing pregnancy, from a very practical standpoint, I think we consider them all the same.

Considering route of administration

OBG Management: Are there benefits associated with transdermal birth control vs other contraceptive options, and are women interested in transdermal contraception?

Dr. Levy: I think there’s always a benefit in having lots of choices. And for some women, being able to put a patch on once a week is much more convenient, easier to remember, and delivers a very consistent dose of hormone absorbed through the skin, which is different than taking a pill in the morning when your levels go up quickly then diminish over the day. The hormones are higher at a certain time, and then they drop off, so there might be some advantages for people who are very sensitive to swings in hormonal levels. There’s also a convenience factor, where for some people they will choose that. Other people might really dislike having a relatively large patch on their skin somewhere, or they may have skin sensitivity to the adhesive. Overall, I always think that having more options is better and individual girls/women will choose what works best for them.

Counseling tips

OBG Management: What are the instructions for patients to effectively use Twirla, and how should they be counseled regarding the expectations for their menstrual cycle?

Dr. Levy: Like other patches that are available on the market, these are a once-a-week patch. The patch should be placed on clean, dry skin. No lotions, perfumes, or anything on the skin because you really want them to stick for the whole week, and it’s not going to stick if there’s anything oily on the skin. The first patch is placed on day 1 of a menstrual cycle, the first day of bleeding, and then changed weekly for 3 weeks. Then there’s a 7-day patch-free time in which one would expect to have a period.

In general, breakthrough bleeding was not a significant problem with the patch, but some women will have some irregular spotting and bleeding with any sort of hormonal treatment; some women may have no periods at all. In other words, the estrogen dose and progestin may be of a balance that allows the patient not to have periods. But, in general, most of the women in the trial had regular light menstrual flow during the week when their patch was not on.⁵

Continue to: Pricing...

Pricing

OBG Management: Are you aware of the current payment options for Twirla? Is it covered by any insurance plans right now?

Dr. Levy: That’s a tricky question. Insurance plans through Obamacare, the Affordable Care Act, are required to cover every form of contraception. That means they must cover a patch. It doesn’t mean that they have to cover this patch. And because there are generics available of the other patch formulation, it is likely that this would be a higher tier, meaning that there may be a higher copay for someone who wanted to use Twirla versus one of the generic patches.

I can’t say that that’s universally the case, but my experience with most of the health insurance plans is that they tend to put barriers in the way for any of us to prescribe, and for women to use, brand-name products. So Twirla is new on the market; it’s a brand-name product. It may work much better for some people; and in those cases, the health care provider might have to send a letter to the insurance company saying why this one is medically necessary for a patient. There probably will be some hoops to go through for coverage without a copay. I think coverage will be there, but there may be a substantial copay because of the tier level.

OBG Management: Do you think that there would be a challenge for someone trying to get a prescription for a patient saying that there is a need because it is a lower dose of estrogen?

Dr. Levy: I don’t think that the payer is going to buy that argument unless the requirement is to use a patch. If the patient, for example, has some sort of gastrointestinal disease where they don’t absorb things well, so pills don’t work well, we might get to the place where they have to have a patch. If the patient has a lot of breast tenderness or has symptoms on the generic patch that delivers a higher level of estrogen, then we would have to document those symptoms to say, “She’s not tolerating this one and, therefore, we need to go to that one.” So, I think as prescribers we would have to justify not only the lower dose but also the form.

As a clinician, I would always like to put somebody on the lower dose. We do think lower is better, but we have to be sensitive to the costs of all of these things too. I’m very sensitive to my patients’ out-of-pocket costs because, in the end, if the costs are a lot of money or she can only afford one month at a time, then she may miss a window where she may not have the money to buy next month’s supply when it’s due, and get pregnant. We have to balance all of those things as we’re thinking through the best option for an individual.

We have more to learn

OBG Management: Is there anything else you would like to add?

Dr. Levy: I think it’s always exciting when we have new products available, and there’s a lot more we’ll learn as Twirla comes into commercial use and millions instead of thousands of people are using it. Overall, I think it’s fantastic that there’s ongoing research and that there are new products out there. And kudos to the company for doing the research and for getting approval, and I’m looking forward to learning more about it.
 

The first transdermal contraceptive patch was approved by the US Food and Drug Administration (FDA) in 2001.¹ A 2018 survey revealed that 5% of women in the United States between the ages of 15 and 49 years reported the use of a short-acting hormonal contraceptive method (ie, vaginal ring, transdermal patch, injectable) within the past month, with just 0.3% reporting the use of a transdermal patch.² Transdermal contraceptive patches are an effective form of birth control that may be a convenient option for patients who do not want to take a daily oral contraceptive pill but want similar efficacy and tolerability. Typical failure rates of patches are similar to that of combined oral contraceptives (COCs).^1,3

While transdermal hormone delivery results in less peaks and troughs of estrogen compared with COCs, the total estrogen exposure is higher than with COCs; therefore, the risk for venous thromboembolism (VTE) with previously available patches is about twice as high.¹ Twirla (Agile), an ethinyl estradiol (EE)/levonorgestrel (LNG) patch, delivers a low and consistent daily dose of hormones over 3 patches replaced once weekly, with no patch on the fourth week.³ Twirla contains 120 μg/day LNG and 30 μg/day EE. OrthoEvra, FDA approved in 2001 as mentioned, contains 150 μg/day norelgestromin and 35 μg/day EE.¹ A reduction of the EE dose in COCs has been associated with lower risk for VTE.⁴

The addition of Twirla to the market offers another contraceptive option for patients who opt for a weekly, self-administered method.

How much lower is the VTE risk?

OBG Management: Can you define what is the reduction in VTE risk for the EE dose in Twirla versus Ortho Evra (a norelgestromin/EE patch) and similar contraceptive patches already available?

Barbara Levy, MD: The reality is we can’t designate a reduction of risk, except, in general, when the dose of ethinyl estradiol is lower, we think that the VTE risk is lower. There has not been a head-to-head comparison in a large enough population to be able to say that the risk is reduced by a certain factor. We just look at the overall exposure to estrogen and say, “In general, for VTE risk, a lower dose is a better thing for women.”

That being said, look at birth control pills, like COCs. We don’t have actual numbers to say that a 30-μg pill is this much less risky than a 35-μg pill. We just put it into a hierarchy, and that’s what we can do with the patch. We can say that, in general, lower is better for VTE risk, but no one can provide absolute numbers.

Continue to: Efficacy...

Efficacy

OBG Management: What is Twirla’s efficacy in preventing pregnancy, and how does this compare to previous patches and other types of hormonal birth control?

Dr. Levy: You have to look at the pivotal trials and look at what the efficacy was in a trial setting. In the real-world setting, the effectiveness is never quite as good as it is in a clinical trial. I think the bottom line for all of us is that combined oral contraception, meaning estrogen with progestin, is equivalently effective across the different options that are available for women. Efficacy really isn’t the factor to use to distinguish which one I’m going to pick. It is about the patient’s convenience and many other factors. But in terms of its clinical effectiveness in preventing pregnancy, from a very practical standpoint, I think we consider them all the same.

Considering route of administration

OBG Management: Are there benefits associated with transdermal birth control vs other contraceptive options, and are women interested in transdermal contraception?

Dr. Levy: I think there’s always a benefit in having lots of choices. And for some women, being able to put a patch on once a week is much more convenient, easier to remember, and delivers a very consistent dose of hormone absorbed through the skin, which is different than taking a pill in the morning when your levels go up quickly then diminish over the day. The hormones are higher at a certain time, and then they drop off, so there might be some advantages for people who are very sensitive to swings in hormonal levels. There’s also a convenience factor, where for some people they will choose that. Other people might really dislike having a relatively large patch on their skin somewhere, or they may have skin sensitivity to the adhesive. Overall, I always think that having more options is better and individual girls/women will choose what works best for them.

Counseling tips

OBG Management: What are the instructions for patients to effectively use Twirla, and how should they be counseled regarding the expectations for their menstrual cycle?

Dr. Levy: Like other patches that are available on the market, these are a once-a-week patch. The patch should be placed on clean, dry skin. No lotions, perfumes, or anything on the skin because you really want them to stick for the whole week, and it’s not going to stick if there’s anything oily on the skin. The first patch is placed on day 1 of a menstrual cycle, the first day of bleeding, and then changed weekly for 3 weeks. Then there’s a 7-day patch-free time in which one would expect to have a period.

In general, breakthrough bleeding was not a significant problem with the patch, but some women will have some irregular spotting and bleeding with any sort of hormonal treatment; some women may have no periods at all. In other words, the estrogen dose and progestin may be of a balance that allows the patient not to have periods. But, in general, most of the women in the trial had regular light menstrual flow during the week when their patch was not on.⁵

Continue to: Pricing...

Pricing

OBG Management: Are you aware of the current payment options for Twirla? Is it covered by any insurance plans right now?

Dr. Levy: That’s a tricky question. Insurance plans through Obamacare, the Affordable Care Act, are required to cover every form of contraception. That means they must cover a patch. It doesn’t mean that they have to cover this patch. And because there are generics available of the other patch formulation, it is likely that this would be a higher tier, meaning that there may be a higher copay for someone who wanted to use Twirla versus one of the generic patches.

I can’t say that that’s universally the case, but my experience with most of the health insurance plans is that they tend to put barriers in the way for any of us to prescribe, and for women to use, brand-name products. So Twirla is new on the market; it’s a brand-name product. It may work much better for some people; and in those cases, the health care provider might have to send a letter to the insurance company saying why this one is medically necessary for a patient. There probably will be some hoops to go through for coverage without a copay. I think coverage will be there, but there may be a substantial copay because of the tier level.

OBG Management: Do you think that there would be a challenge for someone trying to get a prescription for a patient saying that there is a need because it is a lower dose of estrogen?

Dr. Levy: I don’t think that the payer is going to buy that argument unless the requirement is to use a patch. If the patient, for example, has some sort of gastrointestinal disease where they don’t absorb things well, so pills don’t work well, we might get to the place where they have to have a patch. If the patient has a lot of breast tenderness or has symptoms on the generic patch that delivers a higher level of estrogen, then we would have to document those symptoms to say, “She’s not tolerating this one and, therefore, we need to go to that one.” So, I think as prescribers we would have to justify not only the lower dose but also the form.

As a clinician, I would always like to put somebody on the lower dose. We do think lower is better, but we have to be sensitive to the costs of all of these things too. I’m very sensitive to my patients’ out-of-pocket costs because, in the end, if the costs are a lot of money or she can only afford one month at a time, then she may miss a window where she may not have the money to buy next month’s supply when it’s due, and get pregnant. We have to balance all of those things as we’re thinking through the best option for an individual.

We have more to learn

OBG Management: Is there anything else you would like to add?

Dr. Levy: I think it’s always exciting when we have new products available, and there’s a lot more we’ll learn as Twirla comes into commercial use and millions instead of thousands of people are using it. Overall, I think it’s fantastic that there’s ongoing research and that there are new products out there. And kudos to the company for doing the research and for getting approval, and I’m looking forward to learning more about it.
 

Accelerated approvals of oncology drugs based on response data are controversial, because subsequent trials have often failed to show a clinical benefit. This has led to a spate of withdrawals of such accelerated approvals, including those for nivolumab in liver cancer and pembrolizumab in small cell lung cancer.

But one such accelerated approval has now been converted to a full approval, with a small label change, by the Food and Drug Administration.

The new full approval is for pembrolizumab (Keytruda) for first-line use for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy. (The small label change is that mention of PD-L1 status and testing for this have been removed.)

The move is in accordance with recommendations by experts at a recent meeting of the Oncologic Drugs Advisory Committee. They voted 5-3 in favor of this accelerated approval staying. They also voted 10-1 in favor of another immunotherapy, atezolizumab (Tecentriq), for the same indication.

One of the arguments put forward to support these accelerated approvals staying in place is that there is an unmet need in this population of patients who are ineligible for platinum chemotherapy.

But this argument doesn’t hold water – the mere existence of one of these negates the “unmet need” argument for the other, wrote Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Ont., in a commentary on why the FDA’s accelerated approval pathway is broken.

“Even if there is a genuine ‘unmet need’ in a particular setting, these drugs did not meet the standard of improving survival. An unmet need doesn’t imply that the treatment void should be filled with a drug that provides nothing of value to patients,” Dr. Gyawali wrote.

“When we talk about an unmet need, we are speaking of drugs that provide a clinical benefit; any true unmet needs will continue to exist despite maintaining these approvals,” he argued.

After obtaining the accelerated approval for pembrolizumab for patients with bladder cancer who are not eligible for cisplatin-containing chemotherapy, the manufacturer (Merck) carried out a subsequent clinical trial but conducted it in patients who were eligible for platinum-containing chemotherapy (KEYNOTE-361). However, this trial did not meet its prespecified dual primary endpoints of overall survival or progression-free survival in comparison with standard of care chemotherapy, the company noted in a press release.

“We are working with urgency to advance studies to help more patients living with bladder and other types of cancer,” commented Scot Ebbinghaus, MD, vice president of clinical research, Merck Research Laboratories. The company said it has “an extensive clinical development in bladder cancer” and is exploring pembrolizumab use in many settings.

In addition to the new full approval for the first-line indication for patients who are ineligible for platinum chemotherapy, pembrolizumab has two other approved indications in this therapeutic area: the treatment of patients with locally advanced urothelial carcinoma or mUC who experience disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and the treatment of patients with bacillus Calmette-Guérin–unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy.

A version of this article first appeared on Medscape.com.

Accelerated approvals of oncology drugs based on response data are controversial, because subsequent trials have often failed to show a clinical benefit. This has led to a spate of withdrawals of such accelerated approvals, including those for nivolumab in liver cancer and pembrolizumab in small cell lung cancer.

But one such accelerated approval has now been converted to a full approval, with a small label change, by the Food and Drug Administration.

The new full approval is for pembrolizumab (Keytruda) for first-line use for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy. (The small label change is that mention of PD-L1 status and testing for this have been removed.)

The move is in accordance with recommendations by experts at a recent meeting of the Oncologic Drugs Advisory Committee. They voted 5-3 in favor of this accelerated approval staying. They also voted 10-1 in favor of another immunotherapy, atezolizumab (Tecentriq), for the same indication.

One of the arguments put forward to support these accelerated approvals staying in place is that there is an unmet need in this population of patients who are ineligible for platinum chemotherapy.

But this argument doesn’t hold water – the mere existence of one of these negates the “unmet need” argument for the other, wrote Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Ont., in a commentary on why the FDA’s accelerated approval pathway is broken.

“Even if there is a genuine ‘unmet need’ in a particular setting, these drugs did not meet the standard of improving survival. An unmet need doesn’t imply that the treatment void should be filled with a drug that provides nothing of value to patients,” Dr. Gyawali wrote.

“When we talk about an unmet need, we are speaking of drugs that provide a clinical benefit; any true unmet needs will continue to exist despite maintaining these approvals,” he argued.

After obtaining the accelerated approval for pembrolizumab for patients with bladder cancer who are not eligible for cisplatin-containing chemotherapy, the manufacturer (Merck) carried out a subsequent clinical trial but conducted it in patients who were eligible for platinum-containing chemotherapy (KEYNOTE-361). However, this trial did not meet its prespecified dual primary endpoints of overall survival or progression-free survival in comparison with standard of care chemotherapy, the company noted in a press release.

“We are working with urgency to advance studies to help more patients living with bladder and other types of cancer,” commented Scot Ebbinghaus, MD, vice president of clinical research, Merck Research Laboratories. The company said it has “an extensive clinical development in bladder cancer” and is exploring pembrolizumab use in many settings.

In addition to the new full approval for the first-line indication for patients who are ineligible for platinum chemotherapy, pembrolizumab has two other approved indications in this therapeutic area: the treatment of patients with locally advanced urothelial carcinoma or mUC who experience disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and the treatment of patients with bacillus Calmette-Guérin–unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy.

A version of this article first appeared on Medscape.com.

Accelerated approvals of oncology drugs based on response data are controversial, because subsequent trials have often failed to show a clinical benefit. This has led to a spate of withdrawals of such accelerated approvals, including those for nivolumab in liver cancer and pembrolizumab in small cell lung cancer.

But one such accelerated approval has now been converted to a full approval, with a small label change, by the Food and Drug Administration.

The new full approval is for pembrolizumab (Keytruda) for first-line use for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy. (The small label change is that mention of PD-L1 status and testing for this have been removed.)

The move is in accordance with recommendations by experts at a recent meeting of the Oncologic Drugs Advisory Committee. They voted 5-3 in favor of this accelerated approval staying. They also voted 10-1 in favor of another immunotherapy, atezolizumab (Tecentriq), for the same indication.

One of the arguments put forward to support these accelerated approvals staying in place is that there is an unmet need in this population of patients who are ineligible for platinum chemotherapy.

But this argument doesn’t hold water – the mere existence of one of these negates the “unmet need” argument for the other, wrote Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Ont., in a commentary on why the FDA’s accelerated approval pathway is broken.

“Even if there is a genuine ‘unmet need’ in a particular setting, these drugs did not meet the standard of improving survival. An unmet need doesn’t imply that the treatment void should be filled with a drug that provides nothing of value to patients,” Dr. Gyawali wrote.

“When we talk about an unmet need, we are speaking of drugs that provide a clinical benefit; any true unmet needs will continue to exist despite maintaining these approvals,” he argued.

After obtaining the accelerated approval for pembrolizumab for patients with bladder cancer who are not eligible for cisplatin-containing chemotherapy, the manufacturer (Merck) carried out a subsequent clinical trial but conducted it in patients who were eligible for platinum-containing chemotherapy (KEYNOTE-361). However, this trial did not meet its prespecified dual primary endpoints of overall survival or progression-free survival in comparison with standard of care chemotherapy, the company noted in a press release.

“We are working with urgency to advance studies to help more patients living with bladder and other types of cancer,” commented Scot Ebbinghaus, MD, vice president of clinical research, Merck Research Laboratories. The company said it has “an extensive clinical development in bladder cancer” and is exploring pembrolizumab use in many settings.

In addition to the new full approval for the first-line indication for patients who are ineligible for platinum chemotherapy, pembrolizumab has two other approved indications in this therapeutic area: the treatment of patients with locally advanced urothelial carcinoma or mUC who experience disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and the treatment of patients with bacillus Calmette-Guérin–unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy.

A version of this article first appeared on Medscape.com.

Ping. Here’s a picture of your friends on a trip without you. 

Ding. In your inbox, you find an email from your attending dismissing you from a very important project or patient.

Ring. There’s that call from your colleague telling you all about the incredible dinner with some other residents, which you weren’t invited to.

FoMO. Fear of missing out. 

FoMO refers to a social anxiety phenomenon fueled by the need or desire to participate in an experience, event, interaction, or investment. It can be conceptualized in two parts: (1) social ostracism and (2) the need to maintain social connectedness through a sense of belonging and/or strong relationships. It is generally characterized by episodic feelings of regret, discontent, social inferiority, and/or loneliness. 
 

Social networking sites and FoMO

Social networking sites (SNS) are a great way for people to connect instantaneously and without borders. However, they may also decrease the quality of intimate connections and relationships. In the current COVID-19 era of Zoom, most of us could agree that face-to-face and in-person communication triumphs over Internet-based interactions. I can attest that Zoom university, endless FaceTime calls, and late-night Netflix parties are not fulfilling my desire for in-person interactions. That is to say, SNS cannot fully compensate for our unmet social needs. 

In fact, achieving social compensation through SNS may exacerbate social fears and anxiety disorders, and encourage rumination. For example, a recent systematic review investigating social media use among individuals who are socially anxious and lonely found that both of the foregoing factors may lead to greater negative and inhibitory behavior as a result of social media use. In other words, these individuals may experience maladaptive cognitive patterns (for example, rumination) and greater negative social comparison. Feelings of inadequacy can lead to a distorted sense of oneself. 

Ping. Ding. Ring. In 2021, almost half of people in the United States spend 5-6 hours on their phones daily.

Most of us are one click away from what essentially is a “live stream” of continuous updates on peoples’ lives. With these constant updates, we often start to imagine what we’re missing out on: trips, dinners, parties, and everything under the sun. However, in reality, what we see on social media is only a fraction of true reality. For example, that 10-second video of your friend going hiking cannot begin to sum up the entire day. The 24/7 nature of SNS can often lead to a perversion of the truth and unhealthy self-comparisons. 

In this vicious cycle of notifications and constant entertainment, unreasonable expectations are created that adversely impact self-confidence and self-esteem, and may even lead to the emergence of depressive symptoms. 

FoMO and negative associations of SNS go hand in hand. While SNS are a powerful tool for connection and information, they have also been reported to negatively impact quality of interactions.

Next time you see a picture, video, or post of a missed event, perhaps it’s best to stop thinking of the “what ifs” and start crafting your own narrative.
 

Ms Lui completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc candidate. She has received income from Braxia Scientific Corp. A version of this article first appeared on Medscape.com.

Ping. Here’s a picture of your friends on a trip without you. 

Ding. In your inbox, you find an email from your attending dismissing you from a very important project or patient.

Ring. There’s that call from your colleague telling you all about the incredible dinner with some other residents, which you weren’t invited to.

FoMO. Fear of missing out. 

FoMO refers to a social anxiety phenomenon fueled by the need or desire to participate in an experience, event, interaction, or investment. It can be conceptualized in two parts: (1) social ostracism and (2) the need to maintain social connectedness through a sense of belonging and/or strong relationships. It is generally characterized by episodic feelings of regret, discontent, social inferiority, and/or loneliness. 
 

Social networking sites and FoMO

Social networking sites (SNS) are a great way for people to connect instantaneously and without borders. However, they may also decrease the quality of intimate connections and relationships. In the current COVID-19 era of Zoom, most of us could agree that face-to-face and in-person communication triumphs over Internet-based interactions. I can attest that Zoom university, endless FaceTime calls, and late-night Netflix parties are not fulfilling my desire for in-person interactions. That is to say, SNS cannot fully compensate for our unmet social needs. 

In fact, achieving social compensation through SNS may exacerbate social fears and anxiety disorders, and encourage rumination. For example, a recent systematic review investigating social media use among individuals who are socially anxious and lonely found that both of the foregoing factors may lead to greater negative and inhibitory behavior as a result of social media use. In other words, these individuals may experience maladaptive cognitive patterns (for example, rumination) and greater negative social comparison. Feelings of inadequacy can lead to a distorted sense of oneself. 

Ping. Ding. Ring. In 2021, almost half of people in the United States spend 5-6 hours on their phones daily.

Most of us are one click away from what essentially is a “live stream” of continuous updates on peoples’ lives. With these constant updates, we often start to imagine what we’re missing out on: trips, dinners, parties, and everything under the sun. However, in reality, what we see on social media is only a fraction of true reality. For example, that 10-second video of your friend going hiking cannot begin to sum up the entire day. The 24/7 nature of SNS can often lead to a perversion of the truth and unhealthy self-comparisons. 

In this vicious cycle of notifications and constant entertainment, unreasonable expectations are created that adversely impact self-confidence and self-esteem, and may even lead to the emergence of depressive symptoms. 

FoMO and negative associations of SNS go hand in hand. While SNS are a powerful tool for connection and information, they have also been reported to negatively impact quality of interactions.

Next time you see a picture, video, or post of a missed event, perhaps it’s best to stop thinking of the “what ifs” and start crafting your own narrative.
 

Ms Lui completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc candidate. She has received income from Braxia Scientific Corp. A version of this article first appeared on Medscape.com.

Ping. Here’s a picture of your friends on a trip without you. 

Ding. In your inbox, you find an email from your attending dismissing you from a very important project or patient.

Ring. There’s that call from your colleague telling you all about the incredible dinner with some other residents, which you weren’t invited to.

FoMO. Fear of missing out. 

FoMO refers to a social anxiety phenomenon fueled by the need or desire to participate in an experience, event, interaction, or investment. It can be conceptualized in two parts: (1) social ostracism and (2) the need to maintain social connectedness through a sense of belonging and/or strong relationships. It is generally characterized by episodic feelings of regret, discontent, social inferiority, and/or loneliness. 
 

Social networking sites and FoMO

Social networking sites (SNS) are a great way for people to connect instantaneously and without borders. However, they may also decrease the quality of intimate connections and relationships. In the current COVID-19 era of Zoom, most of us could agree that face-to-face and in-person communication triumphs over Internet-based interactions. I can attest that Zoom university, endless FaceTime calls, and late-night Netflix parties are not fulfilling my desire for in-person interactions. That is to say, SNS cannot fully compensate for our unmet social needs. 

In fact, achieving social compensation through SNS may exacerbate social fears and anxiety disorders, and encourage rumination. For example, a recent systematic review investigating social media use among individuals who are socially anxious and lonely found that both of the foregoing factors may lead to greater negative and inhibitory behavior as a result of social media use. In other words, these individuals may experience maladaptive cognitive patterns (for example, rumination) and greater negative social comparison. Feelings of inadequacy can lead to a distorted sense of oneself. 

Ping. Ding. Ring. In 2021, almost half of people in the United States spend 5-6 hours on their phones daily.

Most of us are one click away from what essentially is a “live stream” of continuous updates on peoples’ lives. With these constant updates, we often start to imagine what we’re missing out on: trips, dinners, parties, and everything under the sun. However, in reality, what we see on social media is only a fraction of true reality. For example, that 10-second video of your friend going hiking cannot begin to sum up the entire day. The 24/7 nature of SNS can often lead to a perversion of the truth and unhealthy self-comparisons. 

In this vicious cycle of notifications and constant entertainment, unreasonable expectations are created that adversely impact self-confidence and self-esteem, and may even lead to the emergence of depressive symptoms. 

FoMO and negative associations of SNS go hand in hand. While SNS are a powerful tool for connection and information, they have also been reported to negatively impact quality of interactions.

Next time you see a picture, video, or post of a missed event, perhaps it’s best to stop thinking of the “what ifs” and start crafting your own narrative.
 

Ms Lui completed an HBSc global health specialist degree at the University of Toronto, where she is now an MSc candidate. She has received income from Braxia Scientific Corp. A version of this article first appeared on Medscape.com.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A preprint study finding that the Pfizer-BioNTech mRNA COVID vaccine is associated with an increased risk for cardiac adverse events in teenage boys has elicited a firestorm on Twitter. Although some people issued thoughtful critiques, others lobbed insults against the authors, and still others accused them of either being antivaccine or stoking the fires of the vaccine skeptic movement.

The controversy began soon after the study was posted online September 8 on medRxiv. The authors conclude that for boys, the risk for a cardiac adverse event or hospitalization after the second dose of the Pfizer mRNA vaccine was “considerably higher” than the 120-day risk for hospitalization for COVID-19, “even at times of peak disease prevalence.” This was especially true for those aged 12 to 15 years and even those with no underlying health conditions.

The conclusion – as well as the paper’s source, the Vaccine Adverse Event Reporting System (VAERS), and its methodology, modeled after the Centers for Disease Control and Prevention assessment of the database – did not sit well with many.

“Your methodology hugely overestimates risk, which many commentators who are specialists in the field have highlighted,” tweeted Deepti Gurdasani, senior lecturer in epidemiology at Queen Mary University of London. “Why make this claim when you must know it’s wrong?”

“The authors don’t know what they are doing and they are following their own ideology,” tweeted Boback Ziaeian, MD, PhD, assistant professor of medicine at the University of California, Los Angeles, in the cardiology division. Dr. Ziaeian also tweeted, “I believe the CDC is doing honest work and not dredging slop like you are.”

“Holy shit. Truly terrible methods in that paper,” tweeted Michael Mina, MD, PhD, an epidemiologist and immunologist at the Harvard School of Public Health, Boston, more bluntly.

Some pointed out that VAERS is often used by vaccine skeptics to spread misinformation. “‘Dumpster diving’ describes studies using #VAERS by authors (almost always antivaxxers) who don’t understand its limitations,” tweeted David Gorski, MD, PhD, the editor of Science-Based Medicine, who says in his Twitter bio that he “exposes quackery.”

Added Dr. Gorski: “Doctors fell into this trap with their study suggesting #CovidVaccine is more dangerous to children than #COVID19.”

Dr. Gorski said he did not think that the authors were antivaccine. But, he tweeted, “I’d argue that at least one of the authors (Stevenson) is grossly unqualified to analyze the data. Mandrola? Marginal. The other two *might* be qualified in public health/epi, but they clearly either had no clue about #VAERS limitations or didn’t take them seriously enough.” 

Two of the authors, John Mandrola, MD, a cardiac electrophysiologist who is also a columnist for Medscape, and Tracy Beth Hoeg, MD, PhD, an epidemiologist and sports medicine specialist, told this news organization that their estimates are not definitive, owing to the nature of the VAERS database.

“I want to emphasize that our signal is hypothesis-generating,” said Dr. Mandrola. “There’s obviously more research that needs to be done.” 

“I don’t think it should be used to establish a for-certain rate,” said Dr. Hoeg, about the study. “It’s not a perfect way of establishing what the rate of cardiac adverse events was, but it gives you an estimate, and generally with VAERS, it’s a significant underestimate.”

Both Dr. Hoeg and Dr. Mandrola said their analysis showed enough of a signal that it warranted a rush to publish. “We felt that it was super time-sensitive,” Dr. Mandrola said.
 

Vaccine risks versus COVID harm

The authors searched the VAERS system for children aged 12 to 17 years who had received one or two doses of an mRNA vaccine and had symptoms of myocarditis, pericarditis, myopericarditis, or chest pain, and also troponin levels available in the lab data.

Of the 257 patients they examined, 211 had peak troponin values available for analysis. All but one received the Pfizer vaccine. Results were stratified by age and sex.

The authors found that the rates of cardiac adverse events (CAEs) after dose 1 were 12.0 per million for 12- to 15-year-old boys and 8.2 per million for 16- and 17-year-old boys, compared with 0.0 per million and 2.0 per million for girls the same ages.

The estimates for the 12- to 15-year-old boys were 22% to 150% higher than what the CDC had previously reported.

After the second dose, the rate of CAEs for boys 12 to 15 years was 162.2 per million (143% to 280% higher than the CDC estimate) and for boys 16 and 17 years, it was 94.0 per million, or 30% to 40% higher than CDC estimate.

Dr. Mandrola said he and his colleagues found potentially more cases by using slightly broader search terms than those employed by the CDC but agreed with some critics that a limitation was that they did not call the reporting physicians, as is typical with CDC follow-up on VAERS reports.

The authors point to troponin levels as valid indicators of myocardial damage. Peak troponin levels exceeded 2 ng/mL in 71% of the 12- to 15-year-olds and 82% of 16- and 17-year-olds.

The study shows that for boys 12 to 15 years with no comorbidities, the risk for a CAE after the second dose would be 22.8 times higher than the risk for hospitalization for COVID-19 during periods of low disease burden, 6.0 times higher during periods of moderate transmission, and 4.3 times higher during periods of high transmission.

The authors acknowledge in the paper that their analysis “does not take into account any benefits the vaccine provides against transmission to others, long-term COVID-19 disease risk, or protection from nonsevere COVID-19 symptoms.”

Both Dr. Mandrola and Dr. Hoeg told this news organization that they are currently recalculating their estimates because of the rising numbers of pediatric hospitalizations from the Delta variant surge.
 

Paper rejected by journals

Dr. Hoeg said in an interview that the paper went through peer-review at three journals but was rejected by all three, for reasons that were not made clear.

She and the other authors incorporated the reviewers’ feedback at each turn and included all of their suggestions in the paper that was ultimately uploaded to medRxiv, said Dr. Hoeg.

They decided to put it out as a preprint after the U.S. Food and Drug Administration issued its data and then a warning on June 25 about myocarditis with use of the Pfizer vaccine in children 12 to 15 years of age.

The preprint study was picked up by some media outlets, including The Telegraph and The Guardian newspapers, and tweeted out by vaccine skeptics like Robert W. Malone, MD. 

Rep. Marjorie Taylor Greene (R-Georgia), an outspoken vaccine skeptic, tweeted out the Guardian story saying that the findings mean “there is every reason to stop the covid vaccine mandates.”

Dr. Gorski noted in tweets and in a blog post that one of the paper’s coauthors, Josh Stevenson, is part of Rational Ground, a group that supports the Great Barrington Declaration and is against lockdowns and mask mandates.

Mr. Stevenson did not disclose his affiliation in the paper, and Dr. Hoeg said in an interview that she was unaware of the group and Mr. Stevenson’s association with it and that she did not have the impression that he was altering the data to show any bias.

Both Dr. Mandrola and Dr. Hoeg said they are provaccine and that they were dismayed to find their work being used to support any agenda. “It’s very frustrating,” said Dr. Hoeg, adding that she understands that “when you publish research on a controversial topic, people are going to take it and use it for their agendas.”

Some on Twitter blamed the open and free-wheeling nature of preprints.

Harlan Krumholz, MD, SM, the Harold H. Hines, junior professor of medicine and public health at Yale University, New Haven, Conn., which oversees medRxiv, tweeted, “Do you get that the discussion about the preprint is exactly the purpose of #preprints. So that way when someone claims something, you can look at the source and experts can comment.”

But Dr. Ziaeian tweeted back, “Preprints like this one can be weaponized to stir anti-vaccine lies and damage public health.”

In turn, the Yale physician replied, “Unfortunately these days, almost anything can be weaponized, distorted, misunderstood.” Dr. Krumholz added: “There is no question that this preprint is worthy of deep vetting and discussion. But there is a #preprint artifact to examine.”
 

Measured support

Some clinicians signaled their support for open debate and the preprint’s findings.

“I’ve been very critical of preprints that are too quickly disseminated in the media, and this one is no exception,” tweeted Walid Gellad, MD, MPH, associate professor of medicine at the University of Pittsburgh. “On the other hand, I think the vitriol directed at these authors is wrong,” he added.

“Like it or not, the issue of myocarditis in kids is an issue. Other countries have made vaccination decisions because of this issue, not because they’re driven by some ideology,” he tweeted.

Dr. Gellad also notes that the FDA has estimated the risk could be as high as one in 5,000 and that the preprint numbers could actually be underestimates.

In a long thread, Frank Han, MD, an adult congenital and pediatric cardiologist at the University of Illinois, tweets that relying on the VAERS reports might be faulty and that advanced cardiac imaging – guided by strict criteria – is the best way to determine myocarditis. And, he tweeted, “Physician review of VAERS reports really matters.”

Dr. Han concluded that vaccination “trades in a significant risk with a much smaller risk. That’s what counts in the end.”

In a response, Dr. Mandrola called Han’s tweets “reasoned criticism of our analysis.” He adds that his and Dr. Hoeg’s study have limits, but “our point is not to avoid protecting kids, but how to do so most safely.”

Both Dr. Mandrola and Dr. Hoeg said they welcomed critiques, but they felt blindsided by the vehemence of some of the Twitter debate.

“Some of the vitriol was surprising,” Dr. Mandrola said. “I kind of have this naive notion that people would assume that we’re not bad people,” he added.

However, Dr. Mandrola is known on Twitter for sometimes being highly critical of other researchers’ work, referring to some studies as “howlers,” and has in the past called out others for citing those papers.

Dr. Hoeg said she found critiques about weaknesses in the methods to be helpful. But she said many tweets were “attacking us as people, or not really attacking anything about our study, but just attacking the finding,” which does not help anyone “figure out what we should do about the safety signal or how we can research it further.”

Said Dr. Mandrola: “Why would we just ignore that and go forward with two-shot vaccination as a mandate when other countries are looking at other strategies?”

He noted that the United Kingdom has announced that children 12 to 15 years of age should receive just one shot of the mRNA vaccines instead of two because of the risk for myocarditis. Sixteen- to 18-year-olds have already been advised to get only one dose.

A version of this article first appeared on Medscape.com.

A preprint study finding that the Pfizer-BioNTech mRNA COVID vaccine is associated with an increased risk for cardiac adverse events in teenage boys has elicited a firestorm on Twitter. Although some people issued thoughtful critiques, others lobbed insults against the authors, and still others accused them of either being antivaccine or stoking the fires of the vaccine skeptic movement.

The controversy began soon after the study was posted online September 8 on medRxiv. The authors conclude that for boys, the risk for a cardiac adverse event or hospitalization after the second dose of the Pfizer mRNA vaccine was “considerably higher” than the 120-day risk for hospitalization for COVID-19, “even at times of peak disease prevalence.” This was especially true for those aged 12 to 15 years and even those with no underlying health conditions.

The conclusion – as well as the paper’s source, the Vaccine Adverse Event Reporting System (VAERS), and its methodology, modeled after the Centers for Disease Control and Prevention assessment of the database – did not sit well with many.

“Your methodology hugely overestimates risk, which many commentators who are specialists in the field have highlighted,” tweeted Deepti Gurdasani, senior lecturer in epidemiology at Queen Mary University of London. “Why make this claim when you must know it’s wrong?”

“The authors don’t know what they are doing and they are following their own ideology,” tweeted Boback Ziaeian, MD, PhD, assistant professor of medicine at the University of California, Los Angeles, in the cardiology division. Dr. Ziaeian also tweeted, “I believe the CDC is doing honest work and not dredging slop like you are.”

“Holy shit. Truly terrible methods in that paper,” tweeted Michael Mina, MD, PhD, an epidemiologist and immunologist at the Harvard School of Public Health, Boston, more bluntly.

Some pointed out that VAERS is often used by vaccine skeptics to spread misinformation. “‘Dumpster diving’ describes studies using #VAERS by authors (almost always antivaxxers) who don’t understand its limitations,” tweeted David Gorski, MD, PhD, the editor of Science-Based Medicine, who says in his Twitter bio that he “exposes quackery.”

Added Dr. Gorski: “Doctors fell into this trap with their study suggesting #CovidVaccine is more dangerous to children than #COVID19.”

Dr. Gorski said he did not think that the authors were antivaccine. But, he tweeted, “I’d argue that at least one of the authors (Stevenson) is grossly unqualified to analyze the data. Mandrola? Marginal. The other two *might* be qualified in public health/epi, but they clearly either had no clue about #VAERS limitations or didn’t take them seriously enough.” 

Two of the authors, John Mandrola, MD, a cardiac electrophysiologist who is also a columnist for Medscape, and Tracy Beth Hoeg, MD, PhD, an epidemiologist and sports medicine specialist, told this news organization that their estimates are not definitive, owing to the nature of the VAERS database.

“I want to emphasize that our signal is hypothesis-generating,” said Dr. Mandrola. “There’s obviously more research that needs to be done.” 

“I don’t think it should be used to establish a for-certain rate,” said Dr. Hoeg, about the study. “It’s not a perfect way of establishing what the rate of cardiac adverse events was, but it gives you an estimate, and generally with VAERS, it’s a significant underestimate.”

Both Dr. Hoeg and Dr. Mandrola said their analysis showed enough of a signal that it warranted a rush to publish. “We felt that it was super time-sensitive,” Dr. Mandrola said.
 

Vaccine risks versus COVID harm

The authors searched the VAERS system for children aged 12 to 17 years who had received one or two doses of an mRNA vaccine and had symptoms of myocarditis, pericarditis, myopericarditis, or chest pain, and also troponin levels available in the lab data.

Of the 257 patients they examined, 211 had peak troponin values available for analysis. All but one received the Pfizer vaccine. Results were stratified by age and sex.

The authors found that the rates of cardiac adverse events (CAEs) after dose 1 were 12.0 per million for 12- to 15-year-old boys and 8.2 per million for 16- and 17-year-old boys, compared with 0.0 per million and 2.0 per million for girls the same ages.

The estimates for the 12- to 15-year-old boys were 22% to 150% higher than what the CDC had previously reported.

After the second dose, the rate of CAEs for boys 12 to 15 years was 162.2 per million (143% to 280% higher than the CDC estimate) and for boys 16 and 17 years, it was 94.0 per million, or 30% to 40% higher than CDC estimate.

Dr. Mandrola said he and his colleagues found potentially more cases by using slightly broader search terms than those employed by the CDC but agreed with some critics that a limitation was that they did not call the reporting physicians, as is typical with CDC follow-up on VAERS reports.

The authors point to troponin levels as valid indicators of myocardial damage. Peak troponin levels exceeded 2 ng/mL in 71% of the 12- to 15-year-olds and 82% of 16- and 17-year-olds.

The study shows that for boys 12 to 15 years with no comorbidities, the risk for a CAE after the second dose would be 22.8 times higher than the risk for hospitalization for COVID-19 during periods of low disease burden, 6.0 times higher during periods of moderate transmission, and 4.3 times higher during periods of high transmission.

The authors acknowledge in the paper that their analysis “does not take into account any benefits the vaccine provides against transmission to others, long-term COVID-19 disease risk, or protection from nonsevere COVID-19 symptoms.”

Both Dr. Mandrola and Dr. Hoeg told this news organization that they are currently recalculating their estimates because of the rising numbers of pediatric hospitalizations from the Delta variant surge.
 

Paper rejected by journals

Dr. Hoeg said in an interview that the paper went through peer-review at three journals but was rejected by all three, for reasons that were not made clear.

She and the other authors incorporated the reviewers’ feedback at each turn and included all of their suggestions in the paper that was ultimately uploaded to medRxiv, said Dr. Hoeg.

They decided to put it out as a preprint after the U.S. Food and Drug Administration issued its data and then a warning on June 25 about myocarditis with use of the Pfizer vaccine in children 12 to 15 years of age.

The preprint study was picked up by some media outlets, including The Telegraph and The Guardian newspapers, and tweeted out by vaccine skeptics like Robert W. Malone, MD. 

Rep. Marjorie Taylor Greene (R-Georgia), an outspoken vaccine skeptic, tweeted out the Guardian story saying that the findings mean “there is every reason to stop the covid vaccine mandates.”

Dr. Gorski noted in tweets and in a blog post that one of the paper’s coauthors, Josh Stevenson, is part of Rational Ground, a group that supports the Great Barrington Declaration and is against lockdowns and mask mandates.

Mr. Stevenson did not disclose his affiliation in the paper, and Dr. Hoeg said in an interview that she was unaware of the group and Mr. Stevenson’s association with it and that she did not have the impression that he was altering the data to show any bias.

Both Dr. Mandrola and Dr. Hoeg said they are provaccine and that they were dismayed to find their work being used to support any agenda. “It’s very frustrating,” said Dr. Hoeg, adding that she understands that “when you publish research on a controversial topic, people are going to take it and use it for their agendas.”

Some on Twitter blamed the open and free-wheeling nature of preprints.

Harlan Krumholz, MD, SM, the Harold H. Hines, junior professor of medicine and public health at Yale University, New Haven, Conn., which oversees medRxiv, tweeted, “Do you get that the discussion about the preprint is exactly the purpose of #preprints. So that way when someone claims something, you can look at the source and experts can comment.”

But Dr. Ziaeian tweeted back, “Preprints like this one can be weaponized to stir anti-vaccine lies and damage public health.”

In turn, the Yale physician replied, “Unfortunately these days, almost anything can be weaponized, distorted, misunderstood.” Dr. Krumholz added: “There is no question that this preprint is worthy of deep vetting and discussion. But there is a #preprint artifact to examine.”
 

Measured support

Some clinicians signaled their support for open debate and the preprint’s findings.

“I’ve been very critical of preprints that are too quickly disseminated in the media, and this one is no exception,” tweeted Walid Gellad, MD, MPH, associate professor of medicine at the University of Pittsburgh. “On the other hand, I think the vitriol directed at these authors is wrong,” he added.

“Like it or not, the issue of myocarditis in kids is an issue. Other countries have made vaccination decisions because of this issue, not because they’re driven by some ideology,” he tweeted.

Dr. Gellad also notes that the FDA has estimated the risk could be as high as one in 5,000 and that the preprint numbers could actually be underestimates.

In a long thread, Frank Han, MD, an adult congenital and pediatric cardiologist at the University of Illinois, tweets that relying on the VAERS reports might be faulty and that advanced cardiac imaging – guided by strict criteria – is the best way to determine myocarditis. And, he tweeted, “Physician review of VAERS reports really matters.”

Dr. Han concluded that vaccination “trades in a significant risk with a much smaller risk. That’s what counts in the end.”

In a response, Dr. Mandrola called Han’s tweets “reasoned criticism of our analysis.” He adds that his and Dr. Hoeg’s study have limits, but “our point is not to avoid protecting kids, but how to do so most safely.”

Both Dr. Mandrola and Dr. Hoeg said they welcomed critiques, but they felt blindsided by the vehemence of some of the Twitter debate.

“Some of the vitriol was surprising,” Dr. Mandrola said. “I kind of have this naive notion that people would assume that we’re not bad people,” he added.

However, Dr. Mandrola is known on Twitter for sometimes being highly critical of other researchers’ work, referring to some studies as “howlers,” and has in the past called out others for citing those papers.

Dr. Hoeg said she found critiques about weaknesses in the methods to be helpful. But she said many tweets were “attacking us as people, or not really attacking anything about our study, but just attacking the finding,” which does not help anyone “figure out what we should do about the safety signal or how we can research it further.”

Said Dr. Mandrola: “Why would we just ignore that and go forward with two-shot vaccination as a mandate when other countries are looking at other strategies?”

He noted that the United Kingdom has announced that children 12 to 15 years of age should receive just one shot of the mRNA vaccines instead of two because of the risk for myocarditis. Sixteen- to 18-year-olds have already been advised to get only one dose.

A version of this article first appeared on Medscape.com.

A preprint study finding that the Pfizer-BioNTech mRNA COVID vaccine is associated with an increased risk for cardiac adverse events in teenage boys has elicited a firestorm on Twitter. Although some people issued thoughtful critiques, others lobbed insults against the authors, and still others accused them of either being antivaccine or stoking the fires of the vaccine skeptic movement.

The controversy began soon after the study was posted online September 8 on medRxiv. The authors conclude that for boys, the risk for a cardiac adverse event or hospitalization after the second dose of the Pfizer mRNA vaccine was “considerably higher” than the 120-day risk for hospitalization for COVID-19, “even at times of peak disease prevalence.” This was especially true for those aged 12 to 15 years and even those with no underlying health conditions.

The conclusion – as well as the paper’s source, the Vaccine Adverse Event Reporting System (VAERS), and its methodology, modeled after the Centers for Disease Control and Prevention assessment of the database – did not sit well with many.

“Your methodology hugely overestimates risk, which many commentators who are specialists in the field have highlighted,” tweeted Deepti Gurdasani, senior lecturer in epidemiology at Queen Mary University of London. “Why make this claim when you must know it’s wrong?”

“The authors don’t know what they are doing and they are following their own ideology,” tweeted Boback Ziaeian, MD, PhD, assistant professor of medicine at the University of California, Los Angeles, in the cardiology division. Dr. Ziaeian also tweeted, “I believe the CDC is doing honest work and not dredging slop like you are.”

“Holy shit. Truly terrible methods in that paper,” tweeted Michael Mina, MD, PhD, an epidemiologist and immunologist at the Harvard School of Public Health, Boston, more bluntly.

Some pointed out that VAERS is often used by vaccine skeptics to spread misinformation. “‘Dumpster diving’ describes studies using #VAERS by authors (almost always antivaxxers) who don’t understand its limitations,” tweeted David Gorski, MD, PhD, the editor of Science-Based Medicine, who says in his Twitter bio that he “exposes quackery.”

Added Dr. Gorski: “Doctors fell into this trap with their study suggesting #CovidVaccine is more dangerous to children than #COVID19.”

Dr. Gorski said he did not think that the authors were antivaccine. But, he tweeted, “I’d argue that at least one of the authors (Stevenson) is grossly unqualified to analyze the data. Mandrola? Marginal. The other two *might* be qualified in public health/epi, but they clearly either had no clue about #VAERS limitations or didn’t take them seriously enough.” 

Two of the authors, John Mandrola, MD, a cardiac electrophysiologist who is also a columnist for Medscape, and Tracy Beth Hoeg, MD, PhD, an epidemiologist and sports medicine specialist, told this news organization that their estimates are not definitive, owing to the nature of the VAERS database.

“I want to emphasize that our signal is hypothesis-generating,” said Dr. Mandrola. “There’s obviously more research that needs to be done.” 

“I don’t think it should be used to establish a for-certain rate,” said Dr. Hoeg, about the study. “It’s not a perfect way of establishing what the rate of cardiac adverse events was, but it gives you an estimate, and generally with VAERS, it’s a significant underestimate.”

Both Dr. Hoeg and Dr. Mandrola said their analysis showed enough of a signal that it warranted a rush to publish. “We felt that it was super time-sensitive,” Dr. Mandrola said.
 

Vaccine risks versus COVID harm

The authors searched the VAERS system for children aged 12 to 17 years who had received one or two doses of an mRNA vaccine and had symptoms of myocarditis, pericarditis, myopericarditis, or chest pain, and also troponin levels available in the lab data.

Of the 257 patients they examined, 211 had peak troponin values available for analysis. All but one received the Pfizer vaccine. Results were stratified by age and sex.

The authors found that the rates of cardiac adverse events (CAEs) after dose 1 were 12.0 per million for 12- to 15-year-old boys and 8.2 per million for 16- and 17-year-old boys, compared with 0.0 per million and 2.0 per million for girls the same ages.

The estimates for the 12- to 15-year-old boys were 22% to 150% higher than what the CDC had previously reported.

After the second dose, the rate of CAEs for boys 12 to 15 years was 162.2 per million (143% to 280% higher than the CDC estimate) and for boys 16 and 17 years, it was 94.0 per million, or 30% to 40% higher than CDC estimate.

Dr. Mandrola said he and his colleagues found potentially more cases by using slightly broader search terms than those employed by the CDC but agreed with some critics that a limitation was that they did not call the reporting physicians, as is typical with CDC follow-up on VAERS reports.

The authors point to troponin levels as valid indicators of myocardial damage. Peak troponin levels exceeded 2 ng/mL in 71% of the 12- to 15-year-olds and 82% of 16- and 17-year-olds.

The study shows that for boys 12 to 15 years with no comorbidities, the risk for a CAE after the second dose would be 22.8 times higher than the risk for hospitalization for COVID-19 during periods of low disease burden, 6.0 times higher during periods of moderate transmission, and 4.3 times higher during periods of high transmission.

The authors acknowledge in the paper that their analysis “does not take into account any benefits the vaccine provides against transmission to others, long-term COVID-19 disease risk, or protection from nonsevere COVID-19 symptoms.”

Both Dr. Mandrola and Dr. Hoeg told this news organization that they are currently recalculating their estimates because of the rising numbers of pediatric hospitalizations from the Delta variant surge.
 

Paper rejected by journals

Dr. Hoeg said in an interview that the paper went through peer-review at three journals but was rejected by all three, for reasons that were not made clear.

She and the other authors incorporated the reviewers’ feedback at each turn and included all of their suggestions in the paper that was ultimately uploaded to medRxiv, said Dr. Hoeg.

They decided to put it out as a preprint after the U.S. Food and Drug Administration issued its data and then a warning on June 25 about myocarditis with use of the Pfizer vaccine in children 12 to 15 years of age.

The preprint study was picked up by some media outlets, including The Telegraph and The Guardian newspapers, and tweeted out by vaccine skeptics like Robert W. Malone, MD. 

Rep. Marjorie Taylor Greene (R-Georgia), an outspoken vaccine skeptic, tweeted out the Guardian story saying that the findings mean “there is every reason to stop the covid vaccine mandates.”

Dr. Gorski noted in tweets and in a blog post that one of the paper’s coauthors, Josh Stevenson, is part of Rational Ground, a group that supports the Great Barrington Declaration and is against lockdowns and mask mandates.

Mr. Stevenson did not disclose his affiliation in the paper, and Dr. Hoeg said in an interview that she was unaware of the group and Mr. Stevenson’s association with it and that she did not have the impression that he was altering the data to show any bias.

Both Dr. Mandrola and Dr. Hoeg said they are provaccine and that they were dismayed to find their work being used to support any agenda. “It’s very frustrating,” said Dr. Hoeg, adding that she understands that “when you publish research on a controversial topic, people are going to take it and use it for their agendas.”

Some on Twitter blamed the open and free-wheeling nature of preprints.

Harlan Krumholz, MD, SM, the Harold H. Hines, junior professor of medicine and public health at Yale University, New Haven, Conn., which oversees medRxiv, tweeted, “Do you get that the discussion about the preprint is exactly the purpose of #preprints. So that way when someone claims something, you can look at the source and experts can comment.”

But Dr. Ziaeian tweeted back, “Preprints like this one can be weaponized to stir anti-vaccine lies and damage public health.”

In turn, the Yale physician replied, “Unfortunately these days, almost anything can be weaponized, distorted, misunderstood.” Dr. Krumholz added: “There is no question that this preprint is worthy of deep vetting and discussion. But there is a #preprint artifact to examine.”
 

Measured support

Some clinicians signaled their support for open debate and the preprint’s findings.

“I’ve been very critical of preprints that are too quickly disseminated in the media, and this one is no exception,” tweeted Walid Gellad, MD, MPH, associate professor of medicine at the University of Pittsburgh. “On the other hand, I think the vitriol directed at these authors is wrong,” he added.

“Like it or not, the issue of myocarditis in kids is an issue. Other countries have made vaccination decisions because of this issue, not because they’re driven by some ideology,” he tweeted.

Dr. Gellad also notes that the FDA has estimated the risk could be as high as one in 5,000 and that the preprint numbers could actually be underestimates.

In a long thread, Frank Han, MD, an adult congenital and pediatric cardiologist at the University of Illinois, tweets that relying on the VAERS reports might be faulty and that advanced cardiac imaging – guided by strict criteria – is the best way to determine myocarditis. And, he tweeted, “Physician review of VAERS reports really matters.”

Dr. Han concluded that vaccination “trades in a significant risk with a much smaller risk. That’s what counts in the end.”

In a response, Dr. Mandrola called Han’s tweets “reasoned criticism of our analysis.” He adds that his and Dr. Hoeg’s study have limits, but “our point is not to avoid protecting kids, but how to do so most safely.”

Both Dr. Mandrola and Dr. Hoeg said they welcomed critiques, but they felt blindsided by the vehemence of some of the Twitter debate.

“Some of the vitriol was surprising,” Dr. Mandrola said. “I kind of have this naive notion that people would assume that we’re not bad people,” he added.

However, Dr. Mandrola is known on Twitter for sometimes being highly critical of other researchers’ work, referring to some studies as “howlers,” and has in the past called out others for citing those papers.

Dr. Hoeg said she found critiques about weaknesses in the methods to be helpful. But she said many tweets were “attacking us as people, or not really attacking anything about our study, but just attacking the finding,” which does not help anyone “figure out what we should do about the safety signal or how we can research it further.”

Said Dr. Mandrola: “Why would we just ignore that and go forward with two-shot vaccination as a mandate when other countries are looking at other strategies?”

He noted that the United Kingdom has announced that children 12 to 15 years of age should receive just one shot of the mRNA vaccines instead of two because of the risk for myocarditis. Sixteen- to 18-year-olds have already been advised to get only one dose.

A version of this article first appeared on Medscape.com.

Physicians are bracing for upcoming changes in reimbursement that may start within a few months. As doctors gear up for another wave of COVID, payment trends may not be the top priority, but some “uh oh” announcements in the fall of 2021 could have far-reaching implications that could affect your future.

The Centers for Medicare & Medicaid Services issued a proposed rule in the summer covering key aspects of physician payment. Although the rule contained some small bright lights, the most important changes proposed were far from welcome.

Here’s what could be in store:

1. The highly anticipated Medicare Physician Fee Schedule ruling confirmed a sweeping payment cut. The drive to maintain budget neutrality forced the federal agency to reduce Medicare payments, on average, by nearly 4%. Many physicians are outraged at the proposed cut.

2. More bad news for 2022: Sequestration will be back. Sequestration is the mandatory, pesky, negative 2% adjustment on all Medicare payments. It had been put on hold and is set to return at the beginning of 2022.

Essentially, sequestration reduces what Medicare pays its providers for health services, but Medicare beneficiaries bear no responsibility for the cost difference. To prevent further debt, CMS imposes financially on hospitals, physicians, and other health care providers.

The Health Resources and Services Administration has funds remaining to reimburse for all COVID-related testing, treatment, and vaccines provided to uninsured individuals. You can apply and be reimbursed at Medicare rates for these services when COVID is the primary diagnosis (or secondary in the case of pregnancy). Patients need not be American citizens for you to get paid.

3. Down to a nail-biter: The final ruling is expected in early November. The situation smacks of earlier days when physicians clung to a precipice, waiting in anticipation for a legislative body to save them from the dreaded income plunge. Indeed, we are slipping back to the decade-long period when Congress kept coming to the rescue simply to maintain the status quo.

Many anticipate a last-minute Congressional intervention to save the day, particularly in the midst of another COVID spike. The promises of a stable reimbursement system made possible by the Medicare Access and CHIP Reauthorization Act have been far from realized, and there are signs that the payment landscape is in the midst of a fundamental transformation.

Other changes proposed in the 1,747-page ruling include:
 

Positive:

• More telehealth services will be covered by Medicare, including home visits.
• Tele–mental health services got a big boost; many restrictions were removed so that now the patient’s home is considered a permissible originating site. It also allows for audio-only (no visual required) encounters; the audio-only allowance will extend to opioid use disorder treatment services. Phone treatment is covered.
• Permanent adoption of G2252: The 11- to 20-minute virtual check-in code wasn’t just a one-time payment but will be reimbursed in perpetuity.
• Boosts in reimbursement for chronic care and principal care management codes, which range on the basis of service but indicate a commitment to pay for care coordination.
• Clarification of roles and billing opportunities for split/shared visits, which occur if a physician and advanced practice provider see the same patient on a particular day. Prepare for new coding rules to include a modifier. Previously, the rules for billing were muddled, so transparency helps guide payment opportunities.
• Delay of the appropriate use criteria for advanced imaging for 1 (more) year, a welcome postponement of the ruling that carries a significant administrative burden.
• Physician assistants will be able to bill Medicare directly, and referrals to be made to medical nutrition therapy by a nontreating physician.
• A new approach to patient cost-sharing for colorectal cancer screenings will be phased in. This area has caused problems in the past when the physician identifies a need for additional services (for example, polyp removal by a gastroenterologist during routine colonoscopy).
•  

Not positive:

• Which specialties benefit and which get zapped? The anticipated impact by specialty ranges from hits to interventional radiologists (–9%) and vascular surgeons (–8%), to increases for family practitioners, hand surgeons, endocrinologists, and geriatricians, each estimated to gain a modest 2%. (The exception is portable x-ray supplier, with an estimated increase of 10%.) All other specialties fall in between.
• The proposed conversion factor for 2022 is $33.58, a 3.75% drop from the 2021 conversion factor of $34.89.

The proposed ruling also covered the Quality Payment Program, the overarching program of which the Merit-based Incentive Payment System (MIPS) is the main track for participation. The proposal incorporates additional episode-based cost measures as well as updates to quality indicators and improvement activities.

MIPS penalties. The stakes are higher now, with 9% penalties on the table for nonparticipants. The government offers physicians the ability to officially get out of the program in 2021 because of the COVID-19 pandemic, thereby staving off the steep penalty. The option, which is available through the end of the year, requires a simple application that can be completed on behalf of the entire practice. If you want out, now is the time to find and fill out that application.

Exempt from technology requirements. If the proposal is accepted, small practices – defined by CMS as 15 eligible clinicians or fewer – won’t have to file an annual application to reweight the “promoting interoperability” portion of the program. If acknowledged, small practices will automatically be exempt from the program’s technology section. That’s a big plus, as one of the many chief complaints from small practices is the onus of meeting the technology requirements, which include a security risk analysis, bi-directional health information exchange, public health reporting, and patient access to health information. Meeting the requirements is no small feat. That will only affect future years, so be sure to apply in 2021 if applicable for your practice.

Changes in MIPS. MIPS Value Pathways (MVPs) are anticipated for 2023, with the government releasing details about proposed models for heart disease, rheumatology, joint repair, and more. The MVPs are slated to take over the traditional MIPS by 2027.

The program will shift to 30% of your score coming from the “cost” category, which is based on the government’s analysis of a physician’s claims – and, if attributed, the claims of the patients for whom you care. This area is tricky to manage, but recognize that the costs under scrutiny are the expenses paid by Medicare on behalf of its patients.

In essence, Medicare is measuring the cost of your patients as compared with your colleagues’ costs (in the form of specialty-based benchmarks). Therefore, if you’re referring, or ordering, a more costly set of diagnostic tests, assessments, or interventions than your peers, you’ll be dinged.

However, physicians are more likely this year to flat out reject participation in the federal payment program. Payouts have been paltry and dismal to date, and the buzz is that physicians just don’t consider it worth the effort. Of course, clearing the threshold (which is proposed at 70 points next year) is a must to avoid the penalty, but don’t go crazy to get a perfect score as it won’t count for much. 2022 is the final year that there are any monies for exceptional performance.

Considering that the payouts for exceptional performance have been less than 2% for several years now, it’s hard to justify dedicating resources to achieve perfection. Experts believe that even exceptional performance will only be worth pennies in bonus payments.

The fear of the stick, therefore, may be the only motivation. And that is subjective, as physicians weigh the effort required versus just taking the hit on the penalty. But the penalty is substantial, and so even without the incentive, it’s important to participate at least at the threshold.

Fewer cost-sharing waivers. While the federal government’s payment policies have a major impact on reimbursement, other forces may have broader implications. Commercial payers have rolled back cost-sharing waivers, bringing to light the significant financial responsibility that patients have for their health care in the form of deductibles, coinsurance, and so forth.

More than a third of Americans had trouble paying their health care bills before the pandemic; as patients catch up with services that were postponed or delayed because of the pandemic, this may expose challenges for you. Patients with unpaid bills translate into your financial burden.

Virtual-first health plans. Patients may be seeking alternatives to avoid the frustrating cycle of unpaid medical bills. This may be a factor propelling another trend: Lower-cost virtual-first health plans such as Alignment Health have taken hold in the market. As the name implies, insurance coverage features telehealth that extends to in-person services if necessary.

These disruptors may have their hands at least somewhat tied, however. The market may not be able to fully embrace telemedicine until state licensure is addressed. Despite the federal regulatory relaxations, states still control the distribution of medical care through licensure requirements. Many are rolling back their pandemic-based emergency orders and only allowing licensed physicians to see patients in their state, even over telemedicine.

While seemingly frustrating for physicians who want to see patients over state lines, the delays imposed by states may actually have a welcome effect. If licensure migrates to the federal level, there are many implications. For the purposes of this article, the competitive landscape will become incredibly aggressive. You will need to compete with Amazon Care, Walmart, Cigna, and many other well-funded national players that would love nothing more than to launch a campaign to target the entire nation. Investors are eager to capture part of the nearly quarter-trillion-dollar market, with telemedicine at 38 times prepandemic levels and no signs of abating.

Increased competition for insurers. While the proposed drop in Medicare reimbursement is frustrating, keep a pulse on the fact that your patients may soon be lured by vendors like Amazon and others eager to gain access to physician payments. Instead of analyzing Federal Registers in the future, we may be assessing stock prices.

Consider, therefore, how to ensure that your digital front door is at least available, if not wide open, in the meantime. The nature of physician payments is surely changing.

Ms. Woodcock is president of Woodcock & Associates, Atlanta. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Physicians are bracing for upcoming changes in reimbursement that may start within a few months. As doctors gear up for another wave of COVID, payment trends may not be the top priority, but some “uh oh” announcements in the fall of 2021 could have far-reaching implications that could affect your future.

The Centers for Medicare & Medicaid Services issued a proposed rule in the summer covering key aspects of physician payment. Although the rule contained some small bright lights, the most important changes proposed were far from welcome.

Here’s what could be in store:

1. The highly anticipated Medicare Physician Fee Schedule ruling confirmed a sweeping payment cut. The drive to maintain budget neutrality forced the federal agency to reduce Medicare payments, on average, by nearly 4%. Many physicians are outraged at the proposed cut.

2. More bad news for 2022: Sequestration will be back. Sequestration is the mandatory, pesky, negative 2% adjustment on all Medicare payments. It had been put on hold and is set to return at the beginning of 2022.

Essentially, sequestration reduces what Medicare pays its providers for health services, but Medicare beneficiaries bear no responsibility for the cost difference. To prevent further debt, CMS imposes financially on hospitals, physicians, and other health care providers.

The Health Resources and Services Administration has funds remaining to reimburse for all COVID-related testing, treatment, and vaccines provided to uninsured individuals. You can apply and be reimbursed at Medicare rates for these services when COVID is the primary diagnosis (or secondary in the case of pregnancy). Patients need not be American citizens for you to get paid.

3. Down to a nail-biter: The final ruling is expected in early November. The situation smacks of earlier days when physicians clung to a precipice, waiting in anticipation for a legislative body to save them from the dreaded income plunge. Indeed, we are slipping back to the decade-long period when Congress kept coming to the rescue simply to maintain the status quo.

Many anticipate a last-minute Congressional intervention to save the day, particularly in the midst of another COVID spike. The promises of a stable reimbursement system made possible by the Medicare Access and CHIP Reauthorization Act have been far from realized, and there are signs that the payment landscape is in the midst of a fundamental transformation.

Other changes proposed in the 1,747-page ruling include:
 

Positive:

• More telehealth services will be covered by Medicare, including home visits.
• Tele–mental health services got a big boost; many restrictions were removed so that now the patient’s home is considered a permissible originating site. It also allows for audio-only (no visual required) encounters; the audio-only allowance will extend to opioid use disorder treatment services. Phone treatment is covered.
• Permanent adoption of G2252: The 11- to 20-minute virtual check-in code wasn’t just a one-time payment but will be reimbursed in perpetuity.
• Boosts in reimbursement for chronic care and principal care management codes, which range on the basis of service but indicate a commitment to pay for care coordination.
• Clarification of roles and billing opportunities for split/shared visits, which occur if a physician and advanced practice provider see the same patient on a particular day. Prepare for new coding rules to include a modifier. Previously, the rules for billing were muddled, so transparency helps guide payment opportunities.
• Delay of the appropriate use criteria for advanced imaging for 1 (more) year, a welcome postponement of the ruling that carries a significant administrative burden.
• Physician assistants will be able to bill Medicare directly, and referrals to be made to medical nutrition therapy by a nontreating physician.
• A new approach to patient cost-sharing for colorectal cancer screenings will be phased in. This area has caused problems in the past when the physician identifies a need for additional services (for example, polyp removal by a gastroenterologist during routine colonoscopy).
•  

Not positive:

• Which specialties benefit and which get zapped? The anticipated impact by specialty ranges from hits to interventional radiologists (–9%) and vascular surgeons (–8%), to increases for family practitioners, hand surgeons, endocrinologists, and geriatricians, each estimated to gain a modest 2%. (The exception is portable x-ray supplier, with an estimated increase of 10%.) All other specialties fall in between.
• The proposed conversion factor for 2022 is $33.58, a 3.75% drop from the 2021 conversion factor of $34.89.

The proposed ruling also covered the Quality Payment Program, the overarching program of which the Merit-based Incentive Payment System (MIPS) is the main track for participation. The proposal incorporates additional episode-based cost measures as well as updates to quality indicators and improvement activities.

MIPS penalties. The stakes are higher now, with 9% penalties on the table for nonparticipants. The government offers physicians the ability to officially get out of the program in 2021 because of the COVID-19 pandemic, thereby staving off the steep penalty. The option, which is available through the end of the year, requires a simple application that can be completed on behalf of the entire practice. If you want out, now is the time to find and fill out that application.

Exempt from technology requirements. If the proposal is accepted, small practices – defined by CMS as 15 eligible clinicians or fewer – won’t have to file an annual application to reweight the “promoting interoperability” portion of the program. If acknowledged, small practices will automatically be exempt from the program’s technology section. That’s a big plus, as one of the many chief complaints from small practices is the onus of meeting the technology requirements, which include a security risk analysis, bi-directional health information exchange, public health reporting, and patient access to health information. Meeting the requirements is no small feat. That will only affect future years, so be sure to apply in 2021 if applicable for your practice.

Changes in MIPS. MIPS Value Pathways (MVPs) are anticipated for 2023, with the government releasing details about proposed models for heart disease, rheumatology, joint repair, and more. The MVPs are slated to take over the traditional MIPS by 2027.

The program will shift to 30% of your score coming from the “cost” category, which is based on the government’s analysis of a physician’s claims – and, if attributed, the claims of the patients for whom you care. This area is tricky to manage, but recognize that the costs under scrutiny are the expenses paid by Medicare on behalf of its patients.

In essence, Medicare is measuring the cost of your patients as compared with your colleagues’ costs (in the form of specialty-based benchmarks). Therefore, if you’re referring, or ordering, a more costly set of diagnostic tests, assessments, or interventions than your peers, you’ll be dinged.

However, physicians are more likely this year to flat out reject participation in the federal payment program. Payouts have been paltry and dismal to date, and the buzz is that physicians just don’t consider it worth the effort. Of course, clearing the threshold (which is proposed at 70 points next year) is a must to avoid the penalty, but don’t go crazy to get a perfect score as it won’t count for much. 2022 is the final year that there are any monies for exceptional performance.

Considering that the payouts for exceptional performance have been less than 2% for several years now, it’s hard to justify dedicating resources to achieve perfection. Experts believe that even exceptional performance will only be worth pennies in bonus payments.

The fear of the stick, therefore, may be the only motivation. And that is subjective, as physicians weigh the effort required versus just taking the hit on the penalty. But the penalty is substantial, and so even without the incentive, it’s important to participate at least at the threshold.

Fewer cost-sharing waivers. While the federal government’s payment policies have a major impact on reimbursement, other forces may have broader implications. Commercial payers have rolled back cost-sharing waivers, bringing to light the significant financial responsibility that patients have for their health care in the form of deductibles, coinsurance, and so forth.

More than a third of Americans had trouble paying their health care bills before the pandemic; as patients catch up with services that were postponed or delayed because of the pandemic, this may expose challenges for you. Patients with unpaid bills translate into your financial burden.

Virtual-first health plans. Patients may be seeking alternatives to avoid the frustrating cycle of unpaid medical bills. This may be a factor propelling another trend: Lower-cost virtual-first health plans such as Alignment Health have taken hold in the market. As the name implies, insurance coverage features telehealth that extends to in-person services if necessary.

These disruptors may have their hands at least somewhat tied, however. The market may not be able to fully embrace telemedicine until state licensure is addressed. Despite the federal regulatory relaxations, states still control the distribution of medical care through licensure requirements. Many are rolling back their pandemic-based emergency orders and only allowing licensed physicians to see patients in their state, even over telemedicine.

While seemingly frustrating for physicians who want to see patients over state lines, the delays imposed by states may actually have a welcome effect. If licensure migrates to the federal level, there are many implications. For the purposes of this article, the competitive landscape will become incredibly aggressive. You will need to compete with Amazon Care, Walmart, Cigna, and many other well-funded national players that would love nothing more than to launch a campaign to target the entire nation. Investors are eager to capture part of the nearly quarter-trillion-dollar market, with telemedicine at 38 times prepandemic levels and no signs of abating.

Increased competition for insurers. While the proposed drop in Medicare reimbursement is frustrating, keep a pulse on the fact that your patients may soon be lured by vendors like Amazon and others eager to gain access to physician payments. Instead of analyzing Federal Registers in the future, we may be assessing stock prices.

Consider, therefore, how to ensure that your digital front door is at least available, if not wide open, in the meantime. The nature of physician payments is surely changing.

Ms. Woodcock is president of Woodcock & Associates, Atlanta. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Physicians are bracing for upcoming changes in reimbursement that may start within a few months. As doctors gear up for another wave of COVID, payment trends may not be the top priority, but some “uh oh” announcements in the fall of 2021 could have far-reaching implications that could affect your future.

The Centers for Medicare & Medicaid Services issued a proposed rule in the summer covering key aspects of physician payment. Although the rule contained some small bright lights, the most important changes proposed were far from welcome.

Here’s what could be in store:

1. The highly anticipated Medicare Physician Fee Schedule ruling confirmed a sweeping payment cut. The drive to maintain budget neutrality forced the federal agency to reduce Medicare payments, on average, by nearly 4%. Many physicians are outraged at the proposed cut.

2. More bad news for 2022: Sequestration will be back. Sequestration is the mandatory, pesky, negative 2% adjustment on all Medicare payments. It had been put on hold and is set to return at the beginning of 2022.

Essentially, sequestration reduces what Medicare pays its providers for health services, but Medicare beneficiaries bear no responsibility for the cost difference. To prevent further debt, CMS imposes financially on hospitals, physicians, and other health care providers.

The Health Resources and Services Administration has funds remaining to reimburse for all COVID-related testing, treatment, and vaccines provided to uninsured individuals. You can apply and be reimbursed at Medicare rates for these services when COVID is the primary diagnosis (or secondary in the case of pregnancy). Patients need not be American citizens for you to get paid.

3. Down to a nail-biter: The final ruling is expected in early November. The situation smacks of earlier days when physicians clung to a precipice, waiting in anticipation for a legislative body to save them from the dreaded income plunge. Indeed, we are slipping back to the decade-long period when Congress kept coming to the rescue simply to maintain the status quo.

Many anticipate a last-minute Congressional intervention to save the day, particularly in the midst of another COVID spike. The promises of a stable reimbursement system made possible by the Medicare Access and CHIP Reauthorization Act have been far from realized, and there are signs that the payment landscape is in the midst of a fundamental transformation.

Other changes proposed in the 1,747-page ruling include:
 

Positive:

• More telehealth services will be covered by Medicare, including home visits.
• Tele–mental health services got a big boost; many restrictions were removed so that now the patient’s home is considered a permissible originating site. It also allows for audio-only (no visual required) encounters; the audio-only allowance will extend to opioid use disorder treatment services. Phone treatment is covered.
• Permanent adoption of G2252: The 11- to 20-minute virtual check-in code wasn’t just a one-time payment but will be reimbursed in perpetuity.
• Boosts in reimbursement for chronic care and principal care management codes, which range on the basis of service but indicate a commitment to pay for care coordination.
• Clarification of roles and billing opportunities for split/shared visits, which occur if a physician and advanced practice provider see the same patient on a particular day. Prepare for new coding rules to include a modifier. Previously, the rules for billing were muddled, so transparency helps guide payment opportunities.
• Delay of the appropriate use criteria for advanced imaging for 1 (more) year, a welcome postponement of the ruling that carries a significant administrative burden.
• Physician assistants will be able to bill Medicare directly, and referrals to be made to medical nutrition therapy by a nontreating physician.
• A new approach to patient cost-sharing for colorectal cancer screenings will be phased in. This area has caused problems in the past when the physician identifies a need for additional services (for example, polyp removal by a gastroenterologist during routine colonoscopy).
•  

Not positive:

• Which specialties benefit and which get zapped? The anticipated impact by specialty ranges from hits to interventional radiologists (–9%) and vascular surgeons (–8%), to increases for family practitioners, hand surgeons, endocrinologists, and geriatricians, each estimated to gain a modest 2%. (The exception is portable x-ray supplier, with an estimated increase of 10%.) All other specialties fall in between.
• The proposed conversion factor for 2022 is $33.58, a 3.75% drop from the 2021 conversion factor of $34.89.

The proposed ruling also covered the Quality Payment Program, the overarching program of which the Merit-based Incentive Payment System (MIPS) is the main track for participation. The proposal incorporates additional episode-based cost measures as well as updates to quality indicators and improvement activities.

MIPS penalties. The stakes are higher now, with 9% penalties on the table for nonparticipants. The government offers physicians the ability to officially get out of the program in 2021 because of the COVID-19 pandemic, thereby staving off the steep penalty. The option, which is available through the end of the year, requires a simple application that can be completed on behalf of the entire practice. If you want out, now is the time to find and fill out that application.

Exempt from technology requirements. If the proposal is accepted, small practices – defined by CMS as 15 eligible clinicians or fewer – won’t have to file an annual application to reweight the “promoting interoperability” portion of the program. If acknowledged, small practices will automatically be exempt from the program’s technology section. That’s a big plus, as one of the many chief complaints from small practices is the onus of meeting the technology requirements, which include a security risk analysis, bi-directional health information exchange, public health reporting, and patient access to health information. Meeting the requirements is no small feat. That will only affect future years, so be sure to apply in 2021 if applicable for your practice.

Changes in MIPS. MIPS Value Pathways (MVPs) are anticipated for 2023, with the government releasing details about proposed models for heart disease, rheumatology, joint repair, and more. The MVPs are slated to take over the traditional MIPS by 2027.

The program will shift to 30% of your score coming from the “cost” category, which is based on the government’s analysis of a physician’s claims – and, if attributed, the claims of the patients for whom you care. This area is tricky to manage, but recognize that the costs under scrutiny are the expenses paid by Medicare on behalf of its patients.

In essence, Medicare is measuring the cost of your patients as compared with your colleagues’ costs (in the form of specialty-based benchmarks). Therefore, if you’re referring, or ordering, a more costly set of diagnostic tests, assessments, or interventions than your peers, you’ll be dinged.

However, physicians are more likely this year to flat out reject participation in the federal payment program. Payouts have been paltry and dismal to date, and the buzz is that physicians just don’t consider it worth the effort. Of course, clearing the threshold (which is proposed at 70 points next year) is a must to avoid the penalty, but don’t go crazy to get a perfect score as it won’t count for much. 2022 is the final year that there are any monies for exceptional performance.

Considering that the payouts for exceptional performance have been less than 2% for several years now, it’s hard to justify dedicating resources to achieve perfection. Experts believe that even exceptional performance will only be worth pennies in bonus payments.

The fear of the stick, therefore, may be the only motivation. And that is subjective, as physicians weigh the effort required versus just taking the hit on the penalty. But the penalty is substantial, and so even without the incentive, it’s important to participate at least at the threshold.

Fewer cost-sharing waivers. While the federal government’s payment policies have a major impact on reimbursement, other forces may have broader implications. Commercial payers have rolled back cost-sharing waivers, bringing to light the significant financial responsibility that patients have for their health care in the form of deductibles, coinsurance, and so forth.

More than a third of Americans had trouble paying their health care bills before the pandemic; as patients catch up with services that were postponed or delayed because of the pandemic, this may expose challenges for you. Patients with unpaid bills translate into your financial burden.

Virtual-first health plans. Patients may be seeking alternatives to avoid the frustrating cycle of unpaid medical bills. This may be a factor propelling another trend: Lower-cost virtual-first health plans such as Alignment Health have taken hold in the market. As the name implies, insurance coverage features telehealth that extends to in-person services if necessary.

These disruptors may have their hands at least somewhat tied, however. The market may not be able to fully embrace telemedicine until state licensure is addressed. Despite the federal regulatory relaxations, states still control the distribution of medical care through licensure requirements. Many are rolling back their pandemic-based emergency orders and only allowing licensed physicians to see patients in their state, even over telemedicine.

While seemingly frustrating for physicians who want to see patients over state lines, the delays imposed by states may actually have a welcome effect. If licensure migrates to the federal level, there are many implications. For the purposes of this article, the competitive landscape will become incredibly aggressive. You will need to compete with Amazon Care, Walmart, Cigna, and many other well-funded national players that would love nothing more than to launch a campaign to target the entire nation. Investors are eager to capture part of the nearly quarter-trillion-dollar market, with telemedicine at 38 times prepandemic levels and no signs of abating.

Increased competition for insurers. While the proposed drop in Medicare reimbursement is frustrating, keep a pulse on the fact that your patients may soon be lured by vendors like Amazon and others eager to gain access to physician payments. Instead of analyzing Federal Registers in the future, we may be assessing stock prices.

Consider, therefore, how to ensure that your digital front door is at least available, if not wide open, in the meantime. The nature of physician payments is surely changing.

Ms. Woodcock is president of Woodcock & Associates, Atlanta. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.