MDedge Neurology

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

Use of direct oral anticoagulant drugs (DOACs) appears to be just as effective as warfarin in preventing future thrombotic events in patients with cerebral venous thrombosis (CVT) stroke and are less likely to result in major bleeding, a retrospective study suggests.

The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.

It was also simultaneously published online in Stroke.

“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.

But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.

Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.

Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.

She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.

A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.

A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.

As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.

The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.

The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.

The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.

The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.

The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.

Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.

Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.

When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).

But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).

When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
 

Similar efficacy, better safety

Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”

Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”

“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”

In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”

They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”

They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”

The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.

The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.

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

Use of direct oral anticoagulant drugs (DOACs) appears to be just as effective as warfarin in preventing future thrombotic events in patients with cerebral venous thrombosis (CVT) stroke and are less likely to result in major bleeding, a retrospective study suggests.

The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.

It was also simultaneously published online in Stroke.

“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.

But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.

Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.

Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.

She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.

A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.

A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.

As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.

The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.

The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.

The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.

The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.

The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.

Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.

Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.

When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).

But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).

When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
 

Similar efficacy, better safety

Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”

Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”

“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”

In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”

They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”

They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”

The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.

The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.

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

Use of direct oral anticoagulant drugs (DOACs) appears to be just as effective as warfarin in preventing future thrombotic events in patients with cerebral venous thrombosis (CVT) stroke and are less likely to result in major bleeding, a retrospective study suggests.

The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.

It was also simultaneously published online in Stroke.

“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.

But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.

Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.

Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.

She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.

A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.

A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.

As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.

The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.

The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.

The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.

The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.

The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.

Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.

Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.

When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).

But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).

When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
 

Similar efficacy, better safety

Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”

Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”

“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”

In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”

They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”

They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”

The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.

The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.

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

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

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

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

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

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

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

The insula and frontal cortex are involved in the development of anxiety in adults with Parkinson’s disease, according to imaging data from 108 individuals.

Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.

In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.

Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.

The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.

The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.

The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.

However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.

The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.

The insula and frontal cortex are involved in the development of anxiety in adults with Parkinson’s disease, according to imaging data from 108 individuals.

Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.

In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.

Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.

The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.

The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.

The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.

However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.

The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.

The insula and frontal cortex are involved in the development of anxiety in adults with Parkinson’s disease, according to imaging data from 108 individuals.

Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.

In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.

Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.

The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.

The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.

The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.

However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.

The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.

About 73% of Americans are now immune to the Omicron variant, which could increase to 80% by mid-March, a university health institute says.

About half of eligible Americans have received booster shots, and about 80 million confirmed COVID-19 infections have been reported. Many more infections have occurred but haven’t been officially recorded, The Associated Press reported.

The high percentage of immunity from vaccination and previous infection tends to prevent or shorten new illnesses and reduce the amount of virus circulating overall. Health experts are now discussing whether the number is high enough to stop new waves or reduce the burden on hospitals.

“I am optimistic even if we have a surge in summer, cases will go up, but hospitalizations and deaths will not,” Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington in Seattle, told the AP.

Dr. Mokdad works on COVID-19 forecasting for the university’s Institute for Health Metrics and Evaluation, which has been a reliable model during the pandemic. Dr. Mokdad calculated the 73% number for the AP.

“We have changed,” he said. “We have been exposed to this virus and we know how to deal with it.”

The United States is now reporting about 125,000 new cases per day, according to the data tracker from the New York Times, marking a 68% decrease from the past 2 weeks. Hospitalizations are also down 39%, and about 2,300 new deaths are being reported daily, marking a 13% decline.

There will be more outbreaks as new variants emerge, immunity wanes, and some people remain unvaccinated, Dr. Mokdad said. But the coronavirus is no longer new, and the entire population is no longer “immunologically naive.” Scientists are now trying to understand how long booster protection will last against Omicron and how many people have been infected who had mild or no symptoms that were never reported.

By the end of the Omicron surge, about three out of four people in the United States will have been infected, Shaun Truelove, PhD, an epidemiologist and disease modeler at Johns Hopkins University, told the AP.

“We know it’s a huge proportion of the population,” he said. “This varies a lot by location, and in some areas, we expect the number infected to be closer to one in two.”

That means different regions and groups of people have different levels of protection and risk. In Virginia, for instance, disease modelers estimate that about 45% of residents have the highest level of immunity by being vaccinated and boosted or vaccinated with a recent Omicron infection. Another 47% have immunity that has waned somewhat.

“That’s going to be a nice shield of armor for our population as a whole,” Bryan Lewis, PhD, an epidemiologist who leads the University of Virginia’s COVID-19 modeling team, told the outlet. “If we do get to very low case rates, we certainly can ease back on some of these restrictions.”

About 7% of Virginians are considered the most vulnerable because they were never vaccinated or infected, he noted. Nationwide, about 80 million Americans are still vulnerable, the AP reported.

“The 26% who could still get Omicron right now have to be very careful,” Dr. Mokdad said.

The percentages will continue to change as immunity wanes and new variants circulate in the country. For now, the Institute for Health Metrics and Evaluation model estimates that about 63% to 81% of Americans are protected.

“We’ve reached a much better position for the coming months, but with waning immunity, we shouldn’t take it for granted,” Dr. Mokdad said.

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

About 73% of Americans are now immune to the Omicron variant, which could increase to 80% by mid-March, a university health institute says.

About half of eligible Americans have received booster shots, and about 80 million confirmed COVID-19 infections have been reported. Many more infections have occurred but haven’t been officially recorded, The Associated Press reported.

The high percentage of immunity from vaccination and previous infection tends to prevent or shorten new illnesses and reduce the amount of virus circulating overall. Health experts are now discussing whether the number is high enough to stop new waves or reduce the burden on hospitals.

“I am optimistic even if we have a surge in summer, cases will go up, but hospitalizations and deaths will not,” Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington in Seattle, told the AP.

Dr. Mokdad works on COVID-19 forecasting for the university’s Institute for Health Metrics and Evaluation, which has been a reliable model during the pandemic. Dr. Mokdad calculated the 73% number for the AP.

“We have changed,” he said. “We have been exposed to this virus and we know how to deal with it.”

The United States is now reporting about 125,000 new cases per day, according to the data tracker from the New York Times, marking a 68% decrease from the past 2 weeks. Hospitalizations are also down 39%, and about 2,300 new deaths are being reported daily, marking a 13% decline.

There will be more outbreaks as new variants emerge, immunity wanes, and some people remain unvaccinated, Dr. Mokdad said. But the coronavirus is no longer new, and the entire population is no longer “immunologically naive.” Scientists are now trying to understand how long booster protection will last against Omicron and how many people have been infected who had mild or no symptoms that were never reported.

By the end of the Omicron surge, about three out of four people in the United States will have been infected, Shaun Truelove, PhD, an epidemiologist and disease modeler at Johns Hopkins University, told the AP.

“We know it’s a huge proportion of the population,” he said. “This varies a lot by location, and in some areas, we expect the number infected to be closer to one in two.”

That means different regions and groups of people have different levels of protection and risk. In Virginia, for instance, disease modelers estimate that about 45% of residents have the highest level of immunity by being vaccinated and boosted or vaccinated with a recent Omicron infection. Another 47% have immunity that has waned somewhat.

“That’s going to be a nice shield of armor for our population as a whole,” Bryan Lewis, PhD, an epidemiologist who leads the University of Virginia’s COVID-19 modeling team, told the outlet. “If we do get to very low case rates, we certainly can ease back on some of these restrictions.”

About 7% of Virginians are considered the most vulnerable because they were never vaccinated or infected, he noted. Nationwide, about 80 million Americans are still vulnerable, the AP reported.

“The 26% who could still get Omicron right now have to be very careful,” Dr. Mokdad said.

The percentages will continue to change as immunity wanes and new variants circulate in the country. For now, the Institute for Health Metrics and Evaluation model estimates that about 63% to 81% of Americans are protected.

“We’ve reached a much better position for the coming months, but with waning immunity, we shouldn’t take it for granted,” Dr. Mokdad said.

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

About 73% of Americans are now immune to the Omicron variant, which could increase to 80% by mid-March, a university health institute says.

About half of eligible Americans have received booster shots, and about 80 million confirmed COVID-19 infections have been reported. Many more infections have occurred but haven’t been officially recorded, The Associated Press reported.

The high percentage of immunity from vaccination and previous infection tends to prevent or shorten new illnesses and reduce the amount of virus circulating overall. Health experts are now discussing whether the number is high enough to stop new waves or reduce the burden on hospitals.

“I am optimistic even if we have a surge in summer, cases will go up, but hospitalizations and deaths will not,” Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington in Seattle, told the AP.

Dr. Mokdad works on COVID-19 forecasting for the university’s Institute for Health Metrics and Evaluation, which has been a reliable model during the pandemic. Dr. Mokdad calculated the 73% number for the AP.

“We have changed,” he said. “We have been exposed to this virus and we know how to deal with it.”

The United States is now reporting about 125,000 new cases per day, according to the data tracker from the New York Times, marking a 68% decrease from the past 2 weeks. Hospitalizations are also down 39%, and about 2,300 new deaths are being reported daily, marking a 13% decline.

There will be more outbreaks as new variants emerge, immunity wanes, and some people remain unvaccinated, Dr. Mokdad said. But the coronavirus is no longer new, and the entire population is no longer “immunologically naive.” Scientists are now trying to understand how long booster protection will last against Omicron and how many people have been infected who had mild or no symptoms that were never reported.

By the end of the Omicron surge, about three out of four people in the United States will have been infected, Shaun Truelove, PhD, an epidemiologist and disease modeler at Johns Hopkins University, told the AP.

“We know it’s a huge proportion of the population,” he said. “This varies a lot by location, and in some areas, we expect the number infected to be closer to one in two.”

That means different regions and groups of people have different levels of protection and risk. In Virginia, for instance, disease modelers estimate that about 45% of residents have the highest level of immunity by being vaccinated and boosted or vaccinated with a recent Omicron infection. Another 47% have immunity that has waned somewhat.

“That’s going to be a nice shield of armor for our population as a whole,” Bryan Lewis, PhD, an epidemiologist who leads the University of Virginia’s COVID-19 modeling team, told the outlet. “If we do get to very low case rates, we certainly can ease back on some of these restrictions.”

About 7% of Virginians are considered the most vulnerable because they were never vaccinated or infected, he noted. Nationwide, about 80 million Americans are still vulnerable, the AP reported.

“The 26% who could still get Omicron right now have to be very careful,” Dr. Mokdad said.

The percentages will continue to change as immunity wanes and new variants circulate in the country. For now, the Institute for Health Metrics and Evaluation model estimates that about 63% to 81% of Americans are protected.

“We’ve reached a much better position for the coming months, but with waning immunity, we shouldn’t take it for granted,” Dr. Mokdad said.

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

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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