A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

This time, it didn’t take much persuading for Mary Murphy to embrace home hospice. When her mother was dying from Alzheimer’s disease in 2020, she had been reluctant until she saw what a help it was. So when her husband, Willie, neared the end of his life, she embraced hospice again.

The Murphys’ house in a leafy Nashville, Tenn., neighborhood is their happy place – full of their treasures.

“He’s good to me – buys me anything I want,” she said, as she pulled a milky glass vase out of a floor-to-ceiling cabinet with mirrored shelves.

Willie bought Mary the display case to help her to show off the trinkets she picks up at estate sales.

Down the hall, Willie was lying in their bed, now unable to speak. His heart was giving out.

“You gonna wake up for a minute?” she asked, cradling his head. She patted his back while he cleared his throat. “Cough it out.”

Mary had been the primary caregiver for her husband, but she gets help from a new hospice agency in Nashville focused on increasing the use of end-of-life comfort care by Black families. Heart and Soul Hospice is owned and operated by people who share the same cultural background as the patients they aim to serve.

In their application to obtain a certificate of need in Tennessee, the hospice owners made it clear they are Black and intend to serve everyone but will focus on African Americans, who are currently underserved. Tennessee data shows that in Nashville just 19% of hospice patients are Black, although they make up 27% of the capital city’s population.

Though the area already had numerous hospice agencies, regulators granted Heart and Soul permission to operate, based primarily on the value of educating an underserved group.

In Ms. Murphy’s first hospice experience, her mother had been living with dementia for decades. Still, Ms. Murphy had concerns about transitioning her mother to hospice. She felt as if she was giving up on her mom.

“My first thought was death,” she said.

National data shows that Black Medicare patients and their families are not making the move to comfort care as often as white patients are. Roughly 41% of Black Medicare beneficiaries who died in 2019 were enrolled in hospice, compared with 54% of White patients, according to data compiled annually by the National Hospice and Palliative Care Organization.

Ms. Murphy’s mother survived nearly 3 years on hospice. The benefit is meant for those in the final 6 months of life, but predicting when the end will come is difficult, especially in cases of dementia. Hospice provides palliative care for the dying and support for caregivers for a long as the process lasts.

Ms. Murphy did most of the caregiving – which can be overwhelming – but hospice helped with a few baths a week, medication in the mail and any medical equipment they needed.

And most important to Ms. Murphy was the emotional support, which came mostly from her hospice nurse.

“Wasn’t no doctor going to come here, hold my hand, stay here until the funeral home came for her,” she said about the day her mother died.

Last year, on the day after Thanksgiving, Willie Murphy died. And the same hospice nurse was at the Murphy home within minutes. She’d already stopped by that morning to check on him and returned as soon as Mary called and told her he wasn’t breathing.

“If you don’t feel like: ‘Oh my God, thank God I have hospice,’ if you can’t say that, then we’re doing something wrong,” said Keisha Mason, Heart and Soul’s director of nursing.

Ms. Mason, like Ms. Murphy, is Black and said that in her view there’s nothing fundamental keeping Black patients from using hospice except learning what the service can offer and that it’s basically free to patients – paid for by Medicare, Medicaid, and most private health plans.

“I say to them, ‘If you see a bill, then call us, because you should not,’” she said.

As Ms. Mason helped launch this new hospice agency, she began using new language, calling hospice more than a Medicare benefit. She describes it as an entitlement.

“Just as you are entitled to unemployment, as you are entitled to Social Security, you are entitled to a hospice benefit,” she said.

The investors in Heart and Soul include David Turner, owner of CNS Hospice in Detroit; Nashville pastor the Rev. Sandy McClain; and André Lee, a former hospital administrator on the campus of Meharry Medical College, a historically Black institution in Nashville.

Mr. Lee and Mr. Turner also started a Black-focused hospice agency in Michigan and have plans to replicate the model in other states.

More families need to consider home hospice as an alternative for end-of-life care, Mr. Lee said. Nursing homes are pricey. And even with Medicare, a hospital bill can be hefty.

“You’ll go in there and they’ll eat you alive,” he said. “I hate to say [something] bad about hospitals, but it’s true.”

Hospice research hasn’t come up with clear reasons to explain the gap between White and Black families’ use of the benefit. Some experts speculate it’s related to spiritual beliefs and widespread mistrust in the medical system because of decades of discrimination.

The hospice industry’s national trade group, the National Hospice and Palliative Care Organization, released a diversity and inclusion toolkit and a guide to reaching more Black patients. It recommends connecting with influential DJs, partnering with Black pastors and simply hiring more Black nurses.

Bridging the gap is not overly complicated, Mr. Lee said.

“A lot of hospices don’t employ enough Black people,” he said. “We all feel comfortable when you see someone over there that looks like you.”

Well-established hospice agencies have attempted to minimize barriers with their own diversity initiatives. Michelle Drayton of Visiting Nurse Service of New York said her large agency has met with ministers who counsel families dealing with failing health.

“Many of them did not fully understand what hospice was,” she said. “They had many of the same sort of misperceptions.”

Every hospice company, whether it’s an upstart or one of the nation’s oldest, can promote end-of-life education and ease care disparities, Ms. Drayton said. “We’re not just handing out a brochure,” she added.

This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This time, it didn’t take much persuading for Mary Murphy to embrace home hospice. When her mother was dying from Alzheimer’s disease in 2020, she had been reluctant until she saw what a help it was. So when her husband, Willie, neared the end of his life, she embraced hospice again.

The Murphys’ house in a leafy Nashville, Tenn., neighborhood is their happy place – full of their treasures.

“He’s good to me – buys me anything I want,” she said, as she pulled a milky glass vase out of a floor-to-ceiling cabinet with mirrored shelves.

Willie bought Mary the display case to help her to show off the trinkets she picks up at estate sales.

Down the hall, Willie was lying in their bed, now unable to speak. His heart was giving out.

“You gonna wake up for a minute?” she asked, cradling his head. She patted his back while he cleared his throat. “Cough it out.”

Mary had been the primary caregiver for her husband, but she gets help from a new hospice agency in Nashville focused on increasing the use of end-of-life comfort care by Black families. Heart and Soul Hospice is owned and operated by people who share the same cultural background as the patients they aim to serve.

In their application to obtain a certificate of need in Tennessee, the hospice owners made it clear they are Black and intend to serve everyone but will focus on African Americans, who are currently underserved. Tennessee data shows that in Nashville just 19% of hospice patients are Black, although they make up 27% of the capital city’s population.

Though the area already had numerous hospice agencies, regulators granted Heart and Soul permission to operate, based primarily on the value of educating an underserved group.

In Ms. Murphy’s first hospice experience, her mother had been living with dementia for decades. Still, Ms. Murphy had concerns about transitioning her mother to hospice. She felt as if she was giving up on her mom.

“My first thought was death,” she said.

National data shows that Black Medicare patients and their families are not making the move to comfort care as often as white patients are. Roughly 41% of Black Medicare beneficiaries who died in 2019 were enrolled in hospice, compared with 54% of White patients, according to data compiled annually by the National Hospice and Palliative Care Organization.

Ms. Murphy’s mother survived nearly 3 years on hospice. The benefit is meant for those in the final 6 months of life, but predicting when the end will come is difficult, especially in cases of dementia. Hospice provides palliative care for the dying and support for caregivers for a long as the process lasts.

Ms. Murphy did most of the caregiving – which can be overwhelming – but hospice helped with a few baths a week, medication in the mail and any medical equipment they needed.

And most important to Ms. Murphy was the emotional support, which came mostly from her hospice nurse.

“Wasn’t no doctor going to come here, hold my hand, stay here until the funeral home came for her,” she said about the day her mother died.

Last year, on the day after Thanksgiving, Willie Murphy died. And the same hospice nurse was at the Murphy home within minutes. She’d already stopped by that morning to check on him and returned as soon as Mary called and told her he wasn’t breathing.

“If you don’t feel like: ‘Oh my God, thank God I have hospice,’ if you can’t say that, then we’re doing something wrong,” said Keisha Mason, Heart and Soul’s director of nursing.

Ms. Mason, like Ms. Murphy, is Black and said that in her view there’s nothing fundamental keeping Black patients from using hospice except learning what the service can offer and that it’s basically free to patients – paid for by Medicare, Medicaid, and most private health plans.

“I say to them, ‘If you see a bill, then call us, because you should not,’” she said.

As Ms. Mason helped launch this new hospice agency, she began using new language, calling hospice more than a Medicare benefit. She describes it as an entitlement.

“Just as you are entitled to unemployment, as you are entitled to Social Security, you are entitled to a hospice benefit,” she said.

The investors in Heart and Soul include David Turner, owner of CNS Hospice in Detroit; Nashville pastor the Rev. Sandy McClain; and André Lee, a former hospital administrator on the campus of Meharry Medical College, a historically Black institution in Nashville.

Mr. Lee and Mr. Turner also started a Black-focused hospice agency in Michigan and have plans to replicate the model in other states.

More families need to consider home hospice as an alternative for end-of-life care, Mr. Lee said. Nursing homes are pricey. And even with Medicare, a hospital bill can be hefty.

“You’ll go in there and they’ll eat you alive,” he said. “I hate to say [something] bad about hospitals, but it’s true.”

Hospice research hasn’t come up with clear reasons to explain the gap between White and Black families’ use of the benefit. Some experts speculate it’s related to spiritual beliefs and widespread mistrust in the medical system because of decades of discrimination.

The hospice industry’s national trade group, the National Hospice and Palliative Care Organization, released a diversity and inclusion toolkit and a guide to reaching more Black patients. It recommends connecting with influential DJs, partnering with Black pastors and simply hiring more Black nurses.

Bridging the gap is not overly complicated, Mr. Lee said.

“A lot of hospices don’t employ enough Black people,” he said. “We all feel comfortable when you see someone over there that looks like you.”

Well-established hospice agencies have attempted to minimize barriers with their own diversity initiatives. Michelle Drayton of Visiting Nurse Service of New York said her large agency has met with ministers who counsel families dealing with failing health.

“Many of them did not fully understand what hospice was,” she said. “They had many of the same sort of misperceptions.”

Every hospice company, whether it’s an upstart or one of the nation’s oldest, can promote end-of-life education and ease care disparities, Ms. Drayton said. “We’re not just handing out a brochure,” she added.

This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This time, it didn’t take much persuading for Mary Murphy to embrace home hospice. When her mother was dying from Alzheimer’s disease in 2020, she had been reluctant until she saw what a help it was. So when her husband, Willie, neared the end of his life, she embraced hospice again.

The Murphys’ house in a leafy Nashville, Tenn., neighborhood is their happy place – full of their treasures.

“He’s good to me – buys me anything I want,” she said, as she pulled a milky glass vase out of a floor-to-ceiling cabinet with mirrored shelves.

Willie bought Mary the display case to help her to show off the trinkets she picks up at estate sales.

Down the hall, Willie was lying in their bed, now unable to speak. His heart was giving out.

“You gonna wake up for a minute?” she asked, cradling his head. She patted his back while he cleared his throat. “Cough it out.”

Mary had been the primary caregiver for her husband, but she gets help from a new hospice agency in Nashville focused on increasing the use of end-of-life comfort care by Black families. Heart and Soul Hospice is owned and operated by people who share the same cultural background as the patients they aim to serve.

In their application to obtain a certificate of need in Tennessee, the hospice owners made it clear they are Black and intend to serve everyone but will focus on African Americans, who are currently underserved. Tennessee data shows that in Nashville just 19% of hospice patients are Black, although they make up 27% of the capital city’s population.

Though the area already had numerous hospice agencies, regulators granted Heart and Soul permission to operate, based primarily on the value of educating an underserved group.

In Ms. Murphy’s first hospice experience, her mother had been living with dementia for decades. Still, Ms. Murphy had concerns about transitioning her mother to hospice. She felt as if she was giving up on her mom.

“My first thought was death,” she said.

National data shows that Black Medicare patients and their families are not making the move to comfort care as often as white patients are. Roughly 41% of Black Medicare beneficiaries who died in 2019 were enrolled in hospice, compared with 54% of White patients, according to data compiled annually by the National Hospice and Palliative Care Organization.

Ms. Murphy’s mother survived nearly 3 years on hospice. The benefit is meant for those in the final 6 months of life, but predicting when the end will come is difficult, especially in cases of dementia. Hospice provides palliative care for the dying and support for caregivers for a long as the process lasts.

Ms. Murphy did most of the caregiving – which can be overwhelming – but hospice helped with a few baths a week, medication in the mail and any medical equipment they needed.

And most important to Ms. Murphy was the emotional support, which came mostly from her hospice nurse.

“Wasn’t no doctor going to come here, hold my hand, stay here until the funeral home came for her,” she said about the day her mother died.

Last year, on the day after Thanksgiving, Willie Murphy died. And the same hospice nurse was at the Murphy home within minutes. She’d already stopped by that morning to check on him and returned as soon as Mary called and told her he wasn’t breathing.

“If you don’t feel like: ‘Oh my God, thank God I have hospice,’ if you can’t say that, then we’re doing something wrong,” said Keisha Mason, Heart and Soul’s director of nursing.

Ms. Mason, like Ms. Murphy, is Black and said that in her view there’s nothing fundamental keeping Black patients from using hospice except learning what the service can offer and that it’s basically free to patients – paid for by Medicare, Medicaid, and most private health plans.

“I say to them, ‘If you see a bill, then call us, because you should not,’” she said.

As Ms. Mason helped launch this new hospice agency, she began using new language, calling hospice more than a Medicare benefit. She describes it as an entitlement.

“Just as you are entitled to unemployment, as you are entitled to Social Security, you are entitled to a hospice benefit,” she said.

The investors in Heart and Soul include David Turner, owner of CNS Hospice in Detroit; Nashville pastor the Rev. Sandy McClain; and André Lee, a former hospital administrator on the campus of Meharry Medical College, a historically Black institution in Nashville.

Mr. Lee and Mr. Turner also started a Black-focused hospice agency in Michigan and have plans to replicate the model in other states.

More families need to consider home hospice as an alternative for end-of-life care, Mr. Lee said. Nursing homes are pricey. And even with Medicare, a hospital bill can be hefty.

“You’ll go in there and they’ll eat you alive,” he said. “I hate to say [something] bad about hospitals, but it’s true.”

Hospice research hasn’t come up with clear reasons to explain the gap between White and Black families’ use of the benefit. Some experts speculate it’s related to spiritual beliefs and widespread mistrust in the medical system because of decades of discrimination.

The hospice industry’s national trade group, the National Hospice and Palliative Care Organization, released a diversity and inclusion toolkit and a guide to reaching more Black patients. It recommends connecting with influential DJs, partnering with Black pastors and simply hiring more Black nurses.

Bridging the gap is not overly complicated, Mr. Lee said.

“A lot of hospices don’t employ enough Black people,” he said. “We all feel comfortable when you see someone over there that looks like you.”

Well-established hospice agencies have attempted to minimize barriers with their own diversity initiatives. Michelle Drayton of Visiting Nurse Service of New York said her large agency has met with ministers who counsel families dealing with failing health.

“Many of them did not fully understand what hospice was,” she said. “They had many of the same sort of misperceptions.”

Every hospice company, whether it’s an upstart or one of the nation’s oldest, can promote end-of-life education and ease care disparities, Ms. Drayton said. “We’re not just handing out a brochure,” she added.

This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

The patient is empirically diagnosed with AD complicated by bacterial infection. A skin swab culture is positive for Staphylococcus aureus and Streptococcus pyogenes. 

AD is a common chronic inflammatory skin disease characterized by pruritus, eczematous lesions, xerosis, and lichenification. Individuals of all ages may be affected by AD, although it normally begins in infancy. Studies suggest that as many as 17.1% of adults and 22.6% of children are affected by AD. The disease is associated with diminished quality of life, sleep disturbance, depression, and anxiety. To further complicate matters, patients with AD have a significantly increased risk for recurrent skin infections, including bacterial, viral, and fungal infections. 

The underlying mechanisms of bacterial infection in AD are multifactorial and involve both host and bacterial factors. Factors implicated in the increased risk for infection in patients with AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, and cutaneous dysbiosis. Up to 90% of patients with AD are colonized with S aureus. It has been theorized that the host skin microbiota may play a role in protecting against S aureus colonization and infection in patients with AD. Additionally, bacterial virulence factors, such as the superantigens, proteases, and cytolytic phenol‐soluble modulins secreted by S aureus, trigger skin inflammation and may also contribute to bacterial persistence and/or epithelial penetration and infection.

Overt bacterial infection in patients with AD can be recognized by the presence of weeping lesions, honey‐colored crusts, and pustules. However, cutaneous erythema and warmth, oozing associated with edema, and regional lymphadenopathy are seen in both AD exacerbations and in patients with infection, making clinical diagnosis challenging. In addition, anatomical site‐ and skin type-specific features may disguise signs of infection, and the high frequency of S aureus colonization in AD makes positive skin swab culture of suspected infection an unreliable diagnostic tool. 

S pyogenes is the second most common cause of skin and soft tissue infections in AD (S aureus is the leading cause, although data suggest that pediatric patients are not likely to be affected by superinfections caused by methicillin-resistant S aureus [MRSA]). S pyogenes may cause infections in patients with AD alone or in combination with S aureus. Patients with these skin infections usually present with pustules or impetigo. The lesions may appear as punched-out erosions with scalloped borders that mimic eczema herpeticum or eczema coxsackium. According to guidelines from the American Academy of Dermatology, the presence of purulent exudate and pustules on skin examination may suggest a diagnosis of secondary bacterial infection over inflammation from dermatitis.
 
The use of systemic antibiotics in the treatment of noninfected AD is not recommended; however, systemic antibiotics can be recommended for patients with clinical evidence of bacterial infection, in addition to standard treatment for AD, including the concurrent application of topical steroids. For patients with AD who have signs and symptoms of systemic illness, hospitalization and empirical intravenous antibiotics are recommended. The antibiotic regimen should provide coverage against S aureus because this is the most frequently identified bacterial pathogen in AD. 

When treating critically ill patients, treatment that provides coverage for both MRSA and methicillin-susceptible S aureus (MSSA) with vancomycin and an antistaphylococcal beta-lactam is appropriate. In patients with severe but non–life-threatening infections, vancomycin may be used alone as empirical therapy, pending culture results. Clindamycin can also be considered, particularly if there is no concern for an endovascular infection and the local incidence of clindamycin resistance is less than 15%. 

Bacteremia triggered by S aureus initially requires the use of a bactericidal intravenous agent. For MRSA, vancomycin is the first-line agent. Cefazolin and nafcillin are both acceptable first-line agents for MSSA, although nafcillin can cause venous irritation and phlebitis when administered peripherally. Among children with S aureus bacteremia, an oral agent to which the isolate is susceptible is appropriate, as long as there are no concerns for ongoing bacteremia or endovascular complications. Duration of therapy should be determined by the clinical response; 7-14 days is usually recommended. 

For patients with AD with uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be appropriate pending clinical response or culture and considering local epidemiology and resistance patterns. In patients who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, consideration of coverage for MRSA is recommended. Acceptable oral options for MRSA skin infections in both children and adults include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Finally, topical mupirocin ointment for 5-10 days is an appropriate treatment for patients with AD with minor, localized skin infections such as impetigo. 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier
 

The patient is empirically diagnosed with AD complicated by bacterial infection. A skin swab culture is positive for Staphylococcus aureus and Streptococcus pyogenes. 

AD is a common chronic inflammatory skin disease characterized by pruritus, eczematous lesions, xerosis, and lichenification. Individuals of all ages may be affected by AD, although it normally begins in infancy. Studies suggest that as many as 17.1% of adults and 22.6% of children are affected by AD. The disease is associated with diminished quality of life, sleep disturbance, depression, and anxiety. To further complicate matters, patients with AD have a significantly increased risk for recurrent skin infections, including bacterial, viral, and fungal infections. 

The underlying mechanisms of bacterial infection in AD are multifactorial and involve both host and bacterial factors. Factors implicated in the increased risk for infection in patients with AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, and cutaneous dysbiosis. Up to 90% of patients with AD are colonized with S aureus. It has been theorized that the host skin microbiota may play a role in protecting against S aureus colonization and infection in patients with AD. Additionally, bacterial virulence factors, such as the superantigens, proteases, and cytolytic phenol‐soluble modulins secreted by S aureus, trigger skin inflammation and may also contribute to bacterial persistence and/or epithelial penetration and infection.

Overt bacterial infection in patients with AD can be recognized by the presence of weeping lesions, honey‐colored crusts, and pustules. However, cutaneous erythema and warmth, oozing associated with edema, and regional lymphadenopathy are seen in both AD exacerbations and in patients with infection, making clinical diagnosis challenging. In addition, anatomical site‐ and skin type-specific features may disguise signs of infection, and the high frequency of S aureus colonization in AD makes positive skin swab culture of suspected infection an unreliable diagnostic tool. 

S pyogenes is the second most common cause of skin and soft tissue infections in AD (S aureus is the leading cause, although data suggest that pediatric patients are not likely to be affected by superinfections caused by methicillin-resistant S aureus [MRSA]). S pyogenes may cause infections in patients with AD alone or in combination with S aureus. Patients with these skin infections usually present with pustules or impetigo. The lesions may appear as punched-out erosions with scalloped borders that mimic eczema herpeticum or eczema coxsackium. According to guidelines from the American Academy of Dermatology, the presence of purulent exudate and pustules on skin examination may suggest a diagnosis of secondary bacterial infection over inflammation from dermatitis.
 
The use of systemic antibiotics in the treatment of noninfected AD is not recommended; however, systemic antibiotics can be recommended for patients with clinical evidence of bacterial infection, in addition to standard treatment for AD, including the concurrent application of topical steroids. For patients with AD who have signs and symptoms of systemic illness, hospitalization and empirical intravenous antibiotics are recommended. The antibiotic regimen should provide coverage against S aureus because this is the most frequently identified bacterial pathogen in AD. 

When treating critically ill patients, treatment that provides coverage for both MRSA and methicillin-susceptible S aureus (MSSA) with vancomycin and an antistaphylococcal beta-lactam is appropriate. In patients with severe but non–life-threatening infections, vancomycin may be used alone as empirical therapy, pending culture results. Clindamycin can also be considered, particularly if there is no concern for an endovascular infection and the local incidence of clindamycin resistance is less than 15%. 

Bacteremia triggered by S aureus initially requires the use of a bactericidal intravenous agent. For MRSA, vancomycin is the first-line agent. Cefazolin and nafcillin are both acceptable first-line agents for MSSA, although nafcillin can cause venous irritation and phlebitis when administered peripherally. Among children with S aureus bacteremia, an oral agent to which the isolate is susceptible is appropriate, as long as there are no concerns for ongoing bacteremia or endovascular complications. Duration of therapy should be determined by the clinical response; 7-14 days is usually recommended. 

For patients with AD with uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be appropriate pending clinical response or culture and considering local epidemiology and resistance patterns. In patients who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, consideration of coverage for MRSA is recommended. Acceptable oral options for MRSA skin infections in both children and adults include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Finally, topical mupirocin ointment for 5-10 days is an appropriate treatment for patients with AD with minor, localized skin infections such as impetigo. 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier
 

The patient is empirically diagnosed with AD complicated by bacterial infection. A skin swab culture is positive for Staphylococcus aureus and Streptococcus pyogenes. 

AD is a common chronic inflammatory skin disease characterized by pruritus, eczematous lesions, xerosis, and lichenification. Individuals of all ages may be affected by AD, although it normally begins in infancy. Studies suggest that as many as 17.1% of adults and 22.6% of children are affected by AD. The disease is associated with diminished quality of life, sleep disturbance, depression, and anxiety. To further complicate matters, patients with AD have a significantly increased risk for recurrent skin infections, including bacterial, viral, and fungal infections. 

The underlying mechanisms of bacterial infection in AD are multifactorial and involve both host and bacterial factors. Factors implicated in the increased risk for infection in patients with AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, and cutaneous dysbiosis. Up to 90% of patients with AD are colonized with S aureus. It has been theorized that the host skin microbiota may play a role in protecting against S aureus colonization and infection in patients with AD. Additionally, bacterial virulence factors, such as the superantigens, proteases, and cytolytic phenol‐soluble modulins secreted by S aureus, trigger skin inflammation and may also contribute to bacterial persistence and/or epithelial penetration and infection.

Overt bacterial infection in patients with AD can be recognized by the presence of weeping lesions, honey‐colored crusts, and pustules. However, cutaneous erythema and warmth, oozing associated with edema, and regional lymphadenopathy are seen in both AD exacerbations and in patients with infection, making clinical diagnosis challenging. In addition, anatomical site‐ and skin type-specific features may disguise signs of infection, and the high frequency of S aureus colonization in AD makes positive skin swab culture of suspected infection an unreliable diagnostic tool. 

S pyogenes is the second most common cause of skin and soft tissue infections in AD (S aureus is the leading cause, although data suggest that pediatric patients are not likely to be affected by superinfections caused by methicillin-resistant S aureus [MRSA]). S pyogenes may cause infections in patients with AD alone or in combination with S aureus. Patients with these skin infections usually present with pustules or impetigo. The lesions may appear as punched-out erosions with scalloped borders that mimic eczema herpeticum or eczema coxsackium. According to guidelines from the American Academy of Dermatology, the presence of purulent exudate and pustules on skin examination may suggest a diagnosis of secondary bacterial infection over inflammation from dermatitis.
 
The use of systemic antibiotics in the treatment of noninfected AD is not recommended; however, systemic antibiotics can be recommended for patients with clinical evidence of bacterial infection, in addition to standard treatment for AD, including the concurrent application of topical steroids. For patients with AD who have signs and symptoms of systemic illness, hospitalization and empirical intravenous antibiotics are recommended. The antibiotic regimen should provide coverage against S aureus because this is the most frequently identified bacterial pathogen in AD. 

When treating critically ill patients, treatment that provides coverage for both MRSA and methicillin-susceptible S aureus (MSSA) with vancomycin and an antistaphylococcal beta-lactam is appropriate. In patients with severe but non–life-threatening infections, vancomycin may be used alone as empirical therapy, pending culture results. Clindamycin can also be considered, particularly if there is no concern for an endovascular infection and the local incidence of clindamycin resistance is less than 15%. 

Bacteremia triggered by S aureus initially requires the use of a bactericidal intravenous agent. For MRSA, vancomycin is the first-line agent. Cefazolin and nafcillin are both acceptable first-line agents for MSSA, although nafcillin can cause venous irritation and phlebitis when administered peripherally. Among children with S aureus bacteremia, an oral agent to which the isolate is susceptible is appropriate, as long as there are no concerns for ongoing bacteremia or endovascular complications. Duration of therapy should be determined by the clinical response; 7-14 days is usually recommended. 

For patients with AD with uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be appropriate pending clinical response or culture and considering local epidemiology and resistance patterns. In patients who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, consideration of coverage for MRSA is recommended. Acceptable oral options for MRSA skin infections in both children and adults include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Finally, topical mupirocin ointment for 5-10 days is an appropriate treatment for patients with AD with minor, localized skin infections such as impetigo. 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier
 

Preeclampsia complicates 3% to 8% of pregnancies.^1-3 The incidence of preeclampsia is influenced by the clinical characteristics of the pregnant population, including the prevalence of overweight, obesity, chronic hypertension, diabetes, nulliparity, advanced maternal age, multiple gestations, kidney disease, and a history of preeclampsia in a prior pregnancy.⁴

Magnesium treatment reduces the rate of eclampsia among patients with preeclampsia

For patients with preeclampsia, magnesium treatment reduces the risk of seizure. In the Magpie trial, 9,992 pregnant patients were treated for 24 hours with magnesium or placebo.⁵ The magnesium treatment regimen was either a 4-g IV bolus over 10 to 15 minutes followed by a continuous infusion of 1 g/hr or an intramuscular regimen (10-g intramuscular loading dose followed by 5 g IM every 4 hours). Eclamptic seizures occurred in 0.8% and 1.9% of patients treated with magnesium or placebo, respectively (relative risk [RR], 0.42; 95% confidence interval [CI], 0.29 to 0.60). Among patients with a multiple gestation, the rate of eclampsia was 2% and 6% in the patients treated with magnesium or placebo, respectively. The number of patients who needed to be treated to prevent one eclamptic event was 63 and 109 for patients with preeclampsia with and without severe features, respectively. Intrapartum treatment with magnesium also reduced the risk of placental abruption from 3.2% for the patients receiving placebo to 2.0% among the patients treated with magnesium (RR, 0.67; 99% CI, 0.45- 0.89). Maternal death was reduced with magnesium treatment compared with placebo (0.2% vs 0.4%), but the difference was not statistically significant.

In the Magpie trial, side effects were reported by 24% and 5% of patients treated with magnesium and placebo, respectively. The most common side effects were flushing, nausea, vomiting, and muscle weakness. Of note, magnesium treatment is contraindicated in patients with myasthenia gravis because it can cause muscle weakness and hypoventilation.⁶ For patients with preeclampsia and myasthenia gravis, levetiracetam may be utilized to reduce the risk of seizure.⁶

Duration of postpartum magnesium treatment

There are no studies with a sufficient number of participants to definitively determine the optimal duration of postpartum magnesium therapy. A properly powered study would likely require more than 16,000 to 20,000 participants to identify clinically meaningful differences in the rate of postpartum eclampsia among patients treated with magnesium for 12 or 24 hours.^7,8 It is unlikely that such a study will be completed. Hence, the duration of postpartum magnesium must be based on clinical judgment, balancing the risks and benefits of treatment.

The American College of Obstetricians and Gynecologists (ACOG) recommends continuing magnesium treatment for 24 hours postpartum. They advise, “For patients requiring cesarean delivery (before the onset of labor), the infusion should ideally begin before surgery and continue during surgery, as well as 24 hours afterwards. For patients who deliver vaginally, the infusion should continue for 24 hours after delivery.”⁹

Multiple randomized trials have reported on the outcomes associated with 12 hours versus 24 hours of postpartum magnesium therapy (TABLE). Because the rate of postpartum eclamptic seizure is very low, none of the studies were sufficiently powered to provide a definitive answer to the benefits and harms of the shorter versus longer time frame of magnesium therapy.^10-15

Continue to: The harms of prolonged postpartum magnesium infusion...

The harms of prolonging treatment with postpartum magnesium infusion are generally not emphasized in the medical literature. However, side effects that can occur are flushing, nausea, vomiting, and muscle weakness, delayed early ambulation, delayed return to full diet, delayed discontinuation of a bladder catheter, and delayed initiation of breastfeeding.^5,15 In one large clinical trial, 1,113 patients with preeclampsia with severe features who received intrapartum magnesium for ≥8 hours were randomized after birth to immediate discontinuation of magnesium or continuation of magnesium for 24 hours.¹⁵ There was 1 seizure in the group of 555 patients who received 24 hours of postpartum magnesium and 2 seizures in the group of 558 patients who received no magnesium after birth. In this trial, continuation of magnesium postpartum resulted in delayed initiation of breastfeeding and delayed ambulation.¹⁵

Balancing the benefits and harms of postpartum magnesium infusion

An important clinical point is that magnesium treatment will not prevent all seizures associated with preeclampsia; in the Magpie trial, among the 5,055 patients with preeclampsia treated with magnesium there were 40 (0.8%) seizures.⁵ Magnesium treatment will reduce but not eliminate the risk of seizure. Clinicians should have a plan to treat seizures that occur while a woman is being treated with magnesium.

In the absence of high-quality data to guide the duration of postpartum magnesium therapy it is best to use clinical parameters to balance the benefits and harms of postpartum magnesium treatment.^16-18 Patients may want to participate in the decision about the duration of postpartum magnesium treatment after receiving counseling about the benefits and harms.

For patients with preeclampsia without severe features, many clinicians are no longer ordering intrapartum magnesium for prevention of seizures because they believe the risk of seizure in patients without severe disease is very low. Hence, these patients will not receive postpartum magnesium treatment unless they evolve to preeclampsia with severe features or develop a “red flag” warning postpartum (see below).

For patients with preeclampsia without severe features who received intrapartum magnesium, after birth, the magnesium infusion could be stopped immediately or within 12 hours of birth. For patients with preeclampsia without severe features, early termination of the magnesium infusion best balances the benefit of seizure reduction with the harms of delayed early ambulation, return to full diet, discontinuation of the bladder catheter, and initiation of breastfeeding.

For patients with preeclampsia with severe features, 24 hours of magnesium may best balance the benefits and harms of treatment. However, if the patient continues to have “red flag” findings, continued magnesium treatment beyond 24 hours may be warranted.

Red flag findings include: an eclamptic seizure before or after birth, ongoing or recurring severe headaches, visual scotomata, nausea, vomiting, epigastric pain, severe hypertension, oliguria, rising creatinine, or liver transaminases and declining platelet count.

The hypertensive diseases of pregnancy, including preeclampsia often appear suddenly and may evolve rapidly, threatening the health of both mother and fetus. A high level of suspicion that a hypertensive disease might be the cause of vague symptoms such as epigastric discomfort or headache may accelerate early diagnosis. Rapid treatment of severe hypertension with intravenous labetalol and hydralazine, and intrapartum plus postpartum administration of magnesium to prevent placental abruption and eclampsia will optimize patient outcomes. No patient, patient’s family members, or clinician, wants to experience the grief of a preventable maternal, fetal, or newborn death due to hypertension.¹⁹ Obstetricians, midwives, labor nurses, obstetrical anesthesiologists and doulas play key roles in preventing maternal, fetal, and newborn morbidity and death from hypertensive diseases of pregnancy. As a team we are the last line of defense protecting the health of our patients. ●

Preeclampsia complicates 3% to 8% of pregnancies.^1-3 The incidence of preeclampsia is influenced by the clinical characteristics of the pregnant population, including the prevalence of overweight, obesity, chronic hypertension, diabetes, nulliparity, advanced maternal age, multiple gestations, kidney disease, and a history of preeclampsia in a prior pregnancy.⁴

Magnesium treatment reduces the rate of eclampsia among patients with preeclampsia

For patients with preeclampsia, magnesium treatment reduces the risk of seizure. In the Magpie trial, 9,992 pregnant patients were treated for 24 hours with magnesium or placebo.⁵ The magnesium treatment regimen was either a 4-g IV bolus over 10 to 15 minutes followed by a continuous infusion of 1 g/hr or an intramuscular regimen (10-g intramuscular loading dose followed by 5 g IM every 4 hours). Eclamptic seizures occurred in 0.8% and 1.9% of patients treated with magnesium or placebo, respectively (relative risk [RR], 0.42; 95% confidence interval [CI], 0.29 to 0.60). Among patients with a multiple gestation, the rate of eclampsia was 2% and 6% in the patients treated with magnesium or placebo, respectively. The number of patients who needed to be treated to prevent one eclamptic event was 63 and 109 for patients with preeclampsia with and without severe features, respectively. Intrapartum treatment with magnesium also reduced the risk of placental abruption from 3.2% for the patients receiving placebo to 2.0% among the patients treated with magnesium (RR, 0.67; 99% CI, 0.45- 0.89). Maternal death was reduced with magnesium treatment compared with placebo (0.2% vs 0.4%), but the difference was not statistically significant.

In the Magpie trial, side effects were reported by 24% and 5% of patients treated with magnesium and placebo, respectively. The most common side effects were flushing, nausea, vomiting, and muscle weakness. Of note, magnesium treatment is contraindicated in patients with myasthenia gravis because it can cause muscle weakness and hypoventilation.⁶ For patients with preeclampsia and myasthenia gravis, levetiracetam may be utilized to reduce the risk of seizure.⁶

Duration of postpartum magnesium treatment

There are no studies with a sufficient number of participants to definitively determine the optimal duration of postpartum magnesium therapy. A properly powered study would likely require more than 16,000 to 20,000 participants to identify clinically meaningful differences in the rate of postpartum eclampsia among patients treated with magnesium for 12 or 24 hours.^7,8 It is unlikely that such a study will be completed. Hence, the duration of postpartum magnesium must be based on clinical judgment, balancing the risks and benefits of treatment.

The American College of Obstetricians and Gynecologists (ACOG) recommends continuing magnesium treatment for 24 hours postpartum. They advise, “For patients requiring cesarean delivery (before the onset of labor), the infusion should ideally begin before surgery and continue during surgery, as well as 24 hours afterwards. For patients who deliver vaginally, the infusion should continue for 24 hours after delivery.”⁹

Multiple randomized trials have reported on the outcomes associated with 12 hours versus 24 hours of postpartum magnesium therapy (TABLE). Because the rate of postpartum eclamptic seizure is very low, none of the studies were sufficiently powered to provide a definitive answer to the benefits and harms of the shorter versus longer time frame of magnesium therapy.^10-15

Continue to: The harms of prolonged postpartum magnesium infusion...

The harms of prolonging treatment with postpartum magnesium infusion are generally not emphasized in the medical literature. However, side effects that can occur are flushing, nausea, vomiting, and muscle weakness, delayed early ambulation, delayed return to full diet, delayed discontinuation of a bladder catheter, and delayed initiation of breastfeeding.^5,15 In one large clinical trial, 1,113 patients with preeclampsia with severe features who received intrapartum magnesium for ≥8 hours were randomized after birth to immediate discontinuation of magnesium or continuation of magnesium for 24 hours.¹⁵ There was 1 seizure in the group of 555 patients who received 24 hours of postpartum magnesium and 2 seizures in the group of 558 patients who received no magnesium after birth. In this trial, continuation of magnesium postpartum resulted in delayed initiation of breastfeeding and delayed ambulation.¹⁵

Balancing the benefits and harms of postpartum magnesium infusion

An important clinical point is that magnesium treatment will not prevent all seizures associated with preeclampsia; in the Magpie trial, among the 5,055 patients with preeclampsia treated with magnesium there were 40 (0.8%) seizures.⁵ Magnesium treatment will reduce but not eliminate the risk of seizure. Clinicians should have a plan to treat seizures that occur while a woman is being treated with magnesium.

In the absence of high-quality data to guide the duration of postpartum magnesium therapy it is best to use clinical parameters to balance the benefits and harms of postpartum magnesium treatment.^16-18 Patients may want to participate in the decision about the duration of postpartum magnesium treatment after receiving counseling about the benefits and harms.

For patients with preeclampsia without severe features, many clinicians are no longer ordering intrapartum magnesium for prevention of seizures because they believe the risk of seizure in patients without severe disease is very low. Hence, these patients will not receive postpartum magnesium treatment unless they evolve to preeclampsia with severe features or develop a “red flag” warning postpartum (see below).

For patients with preeclampsia without severe features who received intrapartum magnesium, after birth, the magnesium infusion could be stopped immediately or within 12 hours of birth. For patients with preeclampsia without severe features, early termination of the magnesium infusion best balances the benefit of seizure reduction with the harms of delayed early ambulation, return to full diet, discontinuation of the bladder catheter, and initiation of breastfeeding.

For patients with preeclampsia with severe features, 24 hours of magnesium may best balance the benefits and harms of treatment. However, if the patient continues to have “red flag” findings, continued magnesium treatment beyond 24 hours may be warranted.

Red flag findings include: an eclamptic seizure before or after birth, ongoing or recurring severe headaches, visual scotomata, nausea, vomiting, epigastric pain, severe hypertension, oliguria, rising creatinine, or liver transaminases and declining platelet count.

The hypertensive diseases of pregnancy, including preeclampsia often appear suddenly and may evolve rapidly, threatening the health of both mother and fetus. A high level of suspicion that a hypertensive disease might be the cause of vague symptoms such as epigastric discomfort or headache may accelerate early diagnosis. Rapid treatment of severe hypertension with intravenous labetalol and hydralazine, and intrapartum plus postpartum administration of magnesium to prevent placental abruption and eclampsia will optimize patient outcomes. No patient, patient’s family members, or clinician, wants to experience the grief of a preventable maternal, fetal, or newborn death due to hypertension.¹⁹ Obstetricians, midwives, labor nurses, obstetrical anesthesiologists and doulas play key roles in preventing maternal, fetal, and newborn morbidity and death from hypertensive diseases of pregnancy. As a team we are the last line of defense protecting the health of our patients. ●

Preeclampsia complicates 3% to 8% of pregnancies.^1-3 The incidence of preeclampsia is influenced by the clinical characteristics of the pregnant population, including the prevalence of overweight, obesity, chronic hypertension, diabetes, nulliparity, advanced maternal age, multiple gestations, kidney disease, and a history of preeclampsia in a prior pregnancy.⁴

Magnesium treatment reduces the rate of eclampsia among patients with preeclampsia

For patients with preeclampsia, magnesium treatment reduces the risk of seizure. In the Magpie trial, 9,992 pregnant patients were treated for 24 hours with magnesium or placebo.⁵ The magnesium treatment regimen was either a 4-g IV bolus over 10 to 15 minutes followed by a continuous infusion of 1 g/hr or an intramuscular regimen (10-g intramuscular loading dose followed by 5 g IM every 4 hours). Eclamptic seizures occurred in 0.8% and 1.9% of patients treated with magnesium or placebo, respectively (relative risk [RR], 0.42; 95% confidence interval [CI], 0.29 to 0.60). Among patients with a multiple gestation, the rate of eclampsia was 2% and 6% in the patients treated with magnesium or placebo, respectively. The number of patients who needed to be treated to prevent one eclamptic event was 63 and 109 for patients with preeclampsia with and without severe features, respectively. Intrapartum treatment with magnesium also reduced the risk of placental abruption from 3.2% for the patients receiving placebo to 2.0% among the patients treated with magnesium (RR, 0.67; 99% CI, 0.45- 0.89). Maternal death was reduced with magnesium treatment compared with placebo (0.2% vs 0.4%), but the difference was not statistically significant.

In the Magpie trial, side effects were reported by 24% and 5% of patients treated with magnesium and placebo, respectively. The most common side effects were flushing, nausea, vomiting, and muscle weakness. Of note, magnesium treatment is contraindicated in patients with myasthenia gravis because it can cause muscle weakness and hypoventilation.⁶ For patients with preeclampsia and myasthenia gravis, levetiracetam may be utilized to reduce the risk of seizure.⁶

Duration of postpartum magnesium treatment

There are no studies with a sufficient number of participants to definitively determine the optimal duration of postpartum magnesium therapy. A properly powered study would likely require more than 16,000 to 20,000 participants to identify clinically meaningful differences in the rate of postpartum eclampsia among patients treated with magnesium for 12 or 24 hours.^7,8 It is unlikely that such a study will be completed. Hence, the duration of postpartum magnesium must be based on clinical judgment, balancing the risks and benefits of treatment.

The American College of Obstetricians and Gynecologists (ACOG) recommends continuing magnesium treatment for 24 hours postpartum. They advise, “For patients requiring cesarean delivery (before the onset of labor), the infusion should ideally begin before surgery and continue during surgery, as well as 24 hours afterwards. For patients who deliver vaginally, the infusion should continue for 24 hours after delivery.”⁹

Multiple randomized trials have reported on the outcomes associated with 12 hours versus 24 hours of postpartum magnesium therapy (TABLE). Because the rate of postpartum eclamptic seizure is very low, none of the studies were sufficiently powered to provide a definitive answer to the benefits and harms of the shorter versus longer time frame of magnesium therapy.^10-15

Continue to: The harms of prolonged postpartum magnesium infusion...

The harms of prolonging treatment with postpartum magnesium infusion are generally not emphasized in the medical literature. However, side effects that can occur are flushing, nausea, vomiting, and muscle weakness, delayed early ambulation, delayed return to full diet, delayed discontinuation of a bladder catheter, and delayed initiation of breastfeeding.^5,15 In one large clinical trial, 1,113 patients with preeclampsia with severe features who received intrapartum magnesium for ≥8 hours were randomized after birth to immediate discontinuation of magnesium or continuation of magnesium for 24 hours.¹⁵ There was 1 seizure in the group of 555 patients who received 24 hours of postpartum magnesium and 2 seizures in the group of 558 patients who received no magnesium after birth. In this trial, continuation of magnesium postpartum resulted in delayed initiation of breastfeeding and delayed ambulation.¹⁵

Balancing the benefits and harms of postpartum magnesium infusion

An important clinical point is that magnesium treatment will not prevent all seizures associated with preeclampsia; in the Magpie trial, among the 5,055 patients with preeclampsia treated with magnesium there were 40 (0.8%) seizures.⁵ Magnesium treatment will reduce but not eliminate the risk of seizure. Clinicians should have a plan to treat seizures that occur while a woman is being treated with magnesium.

In the absence of high-quality data to guide the duration of postpartum magnesium therapy it is best to use clinical parameters to balance the benefits and harms of postpartum magnesium treatment.^16-18 Patients may want to participate in the decision about the duration of postpartum magnesium treatment after receiving counseling about the benefits and harms.

For patients with preeclampsia without severe features, many clinicians are no longer ordering intrapartum magnesium for prevention of seizures because they believe the risk of seizure in patients without severe disease is very low. Hence, these patients will not receive postpartum magnesium treatment unless they evolve to preeclampsia with severe features or develop a “red flag” warning postpartum (see below).

For patients with preeclampsia without severe features who received intrapartum magnesium, after birth, the magnesium infusion could be stopped immediately or within 12 hours of birth. For patients with preeclampsia without severe features, early termination of the magnesium infusion best balances the benefit of seizure reduction with the harms of delayed early ambulation, return to full diet, discontinuation of the bladder catheter, and initiation of breastfeeding.

For patients with preeclampsia with severe features, 24 hours of magnesium may best balance the benefits and harms of treatment. However, if the patient continues to have “red flag” findings, continued magnesium treatment beyond 24 hours may be warranted.

Red flag findings include: an eclamptic seizure before or after birth, ongoing or recurring severe headaches, visual scotomata, nausea, vomiting, epigastric pain, severe hypertension, oliguria, rising creatinine, or liver transaminases and declining platelet count.

The hypertensive diseases of pregnancy, including preeclampsia often appear suddenly and may evolve rapidly, threatening the health of both mother and fetus. A high level of suspicion that a hypertensive disease might be the cause of vague symptoms such as epigastric discomfort or headache may accelerate early diagnosis. Rapid treatment of severe hypertension with intravenous labetalol and hydralazine, and intrapartum plus postpartum administration of magnesium to prevent placental abruption and eclampsia will optimize patient outcomes. No patient, patient’s family members, or clinician, wants to experience the grief of a preventable maternal, fetal, or newborn death due to hypertension.¹⁹ Obstetricians, midwives, labor nurses, obstetrical anesthesiologists and doulas play key roles in preventing maternal, fetal, and newborn morbidity and death from hypertensive diseases of pregnancy. As a team we are the last line of defense protecting the health of our patients. ●

Lack of a high school education is a predictor of whether a person will be resistant to getting the COVID-19 vaccine, a new study shows.

Researchers from the University of North Carolina looked at vaccination rates in 3,142 counties in the U.S. They compared them to population characteristics based on the CDC Social Vulnerability Index.

They found that more than half of the unvaccinated adults in the U.S. with strong vaccine hesitancy had a high school education or less. Vaccine hesitancy was defined as refusal to be vaccinated even if the COVID-19 vaccine was available.

The other main predictor for vaccine hesitancy was concern about vaccine availability and distribution, the researchers said.

“Our study suggests that low education levels are a major contributor to vaccine hesitancy and ultimately vaccination levels,” the authors wrote. The study was published in the American Journal of Infection Control. “Specifically, low vaccination levels were found in communities with a less educated population and with more concern about vaccine uptake capacity, suggesting that education is an ongoing challenge.”

“Our findings suggest that policy makers and community leaders should tailor vaccine information and efforts to those with limited education and specifically address knowledge concerns that are prevalent and likely more modifiable.”

The study was based on data gathered months ago. It says that as of May 9, 2021, 34.7% of the U.S. population was fully vaccinated and that 8% reported a strong unwillingness to get vaccinated.

At press time, the Centers for Disease Control and Prevention’s COVID Data Tracker showed that 62.5% of the U.S. population was fully vaccinated.

According to the study, other consistent characteristics of people who are vaccine hesitant are that they belong to a racial minority, are 65 or older, live in a household with children 18 or younger, or are unemployed.

When asked why they were vaccine hesitant, people gave these reasons: Lack of trust in COVID-19 vaccines (55%), concerns about side effects (48%), and lack of trust in government (46%).

Lack of access to vaccines, often cited in previous studies about resistance to other vaccines, was not cited as a reason for not getting the COVID-19 vaccine.

“COVID-19 vaccine hesitancy is a public health threat,” the researchers concluded. “Since education levels are not easily modifiable, our results suggest that policymakers would be best served by closing knowledge gaps to overcome negative perceptions of the vaccine through tailored interventions.”

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

Lack of a high school education is a predictor of whether a person will be resistant to getting the COVID-19 vaccine, a new study shows.

Researchers from the University of North Carolina looked at vaccination rates in 3,142 counties in the U.S. They compared them to population characteristics based on the CDC Social Vulnerability Index.

They found that more than half of the unvaccinated adults in the U.S. with strong vaccine hesitancy had a high school education or less. Vaccine hesitancy was defined as refusal to be vaccinated even if the COVID-19 vaccine was available.

The other main predictor for vaccine hesitancy was concern about vaccine availability and distribution, the researchers said.

“Our study suggests that low education levels are a major contributor to vaccine hesitancy and ultimately vaccination levels,” the authors wrote. The study was published in the American Journal of Infection Control. “Specifically, low vaccination levels were found in communities with a less educated population and with more concern about vaccine uptake capacity, suggesting that education is an ongoing challenge.”

“Our findings suggest that policy makers and community leaders should tailor vaccine information and efforts to those with limited education and specifically address knowledge concerns that are prevalent and likely more modifiable.”

The study was based on data gathered months ago. It says that as of May 9, 2021, 34.7% of the U.S. population was fully vaccinated and that 8% reported a strong unwillingness to get vaccinated.

At press time, the Centers for Disease Control and Prevention’s COVID Data Tracker showed that 62.5% of the U.S. population was fully vaccinated.

According to the study, other consistent characteristics of people who are vaccine hesitant are that they belong to a racial minority, are 65 or older, live in a household with children 18 or younger, or are unemployed.

When asked why they were vaccine hesitant, people gave these reasons: Lack of trust in COVID-19 vaccines (55%), concerns about side effects (48%), and lack of trust in government (46%).

Lack of access to vaccines, often cited in previous studies about resistance to other vaccines, was not cited as a reason for not getting the COVID-19 vaccine.

“COVID-19 vaccine hesitancy is a public health threat,” the researchers concluded. “Since education levels are not easily modifiable, our results suggest that policymakers would be best served by closing knowledge gaps to overcome negative perceptions of the vaccine through tailored interventions.”

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

Lack of a high school education is a predictor of whether a person will be resistant to getting the COVID-19 vaccine, a new study shows.

Researchers from the University of North Carolina looked at vaccination rates in 3,142 counties in the U.S. They compared them to population characteristics based on the CDC Social Vulnerability Index.

They found that more than half of the unvaccinated adults in the U.S. with strong vaccine hesitancy had a high school education or less. Vaccine hesitancy was defined as refusal to be vaccinated even if the COVID-19 vaccine was available.

The other main predictor for vaccine hesitancy was concern about vaccine availability and distribution, the researchers said.

“Our study suggests that low education levels are a major contributor to vaccine hesitancy and ultimately vaccination levels,” the authors wrote. The study was published in the American Journal of Infection Control. “Specifically, low vaccination levels were found in communities with a less educated population and with more concern about vaccine uptake capacity, suggesting that education is an ongoing challenge.”

“Our findings suggest that policy makers and community leaders should tailor vaccine information and efforts to those with limited education and specifically address knowledge concerns that are prevalent and likely more modifiable.”

The study was based on data gathered months ago. It says that as of May 9, 2021, 34.7% of the U.S. population was fully vaccinated and that 8% reported a strong unwillingness to get vaccinated.

At press time, the Centers for Disease Control and Prevention’s COVID Data Tracker showed that 62.5% of the U.S. population was fully vaccinated.

According to the study, other consistent characteristics of people who are vaccine hesitant are that they belong to a racial minority, are 65 or older, live in a household with children 18 or younger, or are unemployed.

When asked why they were vaccine hesitant, people gave these reasons: Lack of trust in COVID-19 vaccines (55%), concerns about side effects (48%), and lack of trust in government (46%).

Lack of access to vaccines, often cited in previous studies about resistance to other vaccines, was not cited as a reason for not getting the COVID-19 vaccine.

“COVID-19 vaccine hesitancy is a public health threat,” the researchers concluded. “Since education levels are not easily modifiable, our results suggest that policymakers would be best served by closing knowledge gaps to overcome negative perceptions of the vaccine through tailored interventions.”

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