The Veterans Health Administration (VHA) COVID-19 vaccine allocation plan showcases several lessons for government and health care leaders in planning for future pandemics.¹ Many state governments—underresourced and overwhelmed with other COVID-19 demands—have struggled to get COVID-19 vaccines into the arms of their residents.² In contrast, the VHA was able to mobilize early to identify vaccine allocation guidelines and proactively prepare facilities to vaccinate VHA staff and veterans as soon as vaccines were approved under Emergency Use Authorization by the US Food and Drug Administration.^3,4

In August 2020, VHA formed a COVID-19 Vaccine Integrated Project Team, composed of 6 subgroups: communications, distribution, education, measurement, policy, prioritization, and vaccine safety. The National Center for Ethics in Health Care weighed in on the ethical justification for the developed vaccination risk stratification framework, which was informed by, but not identical to, that recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.⁵

Prioritizing who gets early access to a potentially life-saving vaccine weighs heavily on those leaders charged with making such decisions. The ethics of scarce resource allocation and triage protocols that may be necessary in a pandemic are often in tension with the patient-centered clinical ethics that health care practitioners (HCPs) encounter. HCPs require assistance in appreciating the ethical rationale for this shift in focus from the preference of the individual to the common good. The same is true for the risk stratification criteria required when there is not sufficient vaccine for all those who could benefit from immunization. Decisions must be transparent to ensure widespread acceptance and trust in the vaccination process. The ethical reasoning and values that are the basis for allocation criteria must be clearly, compassionately, and consistently communicated to the public, as outlined below. Ethical questions or concerns involve a conflict between core values: one of the central tasks of ethical analysis is to identify the available ethical options to resolve value conflicts. Several ethical frameworks for vaccine allocation are available—each balances and weighs the primary values of equity, dignity, beneficence, and utility slightly differently.⁶

For example, utilitarian ethics looks to produce the most good and avoid the most harm for the greatest number of people. Within this framework, there can be different notions of “good,” for example, saving the most lives, the most life years, the most quality life years, or the lives of those who have more life “innings” ahead. The approach of the US Department of Veterans Affairs (VA) focuses on saving the most lives in combination with avoiding suffering from serious illness, minimizing contagion, and preserving the essential workforce. Frameworks that give primacy to 1 notion of the good (ie, saving the most lives) may deprioritize other beneficial outcomes, such as allowing earlier return to work, school, and leisure activities that many find integral to human flourishing. Other ethical theories and principles may be used to support various allocation frameworks. For example, a pragmatic ethics approach might emphasize the importance of adapting the approach based on the evolving science and innovation surrounding COVID-19. Having more than 1 ethically defensible approach is common; the goal in ethics work is to be open to diversity of thought and reflect on the strength of one’s reasoning in resolving a core values conflict. We identify 2 central tenets of pandemic ethics that inform vaccine allocation.

1. Pandemic Ethics Requires Proactive Planning and Reevaluation of Continually Evolving Facts

There is an oft quoted saying among bioethicists: “Good ethics begins with good facts.” One obvious challenge during the COVID-19 pandemic has been the difficulty accessing up-to-date facts to inform decision making. If a main goal of a vaccination plan is to minimize the incidence of serious or fatal COVID-19 disease and contagion, myriad data points are needed to identify the best way to do this. For example, if 2 doses of the same vaccine are needed, this impacts the logistics of identifying, inviting, and scheduling eligible individuals and staffing vaccine clinics as well as ensuring that sufficient personal protective equipment and rescue equipment/medication are available to treat allergic reactions. If the adverse effects of vaccines lead to staff absenteeism or vaccine hesitancy, this needs to be factored into logistics.⁷ Tailored messaging is important to reduce appointment no-shows and vaccine nonadopters.⁸ Transportation to vaccination sites is a relevant factor: how a vaccine is stored, thawed, and reconstituted and its shelf life impacts whether it can be transported after thawing and what must be provided on site.

Consideration of the multifaceted factors influencing a successful vaccination campaign requires proactive planning and the readiness to pivot when new information is revealed. For example, vaccine appointment no-shows should be anticipated along with a fair process for allocating unused vaccine that would otherwise be wasted. This is an example of responsible stewardship of a scarce and life-saving resource. A higher than anticipated no-show rate would require revisiting a facility’s approach to ensuring that waste is avoided while the process is perceived to be fair and transparent. Ethical theories and principles cannot do all the work here; mindful attention to detail and proactive, informed planning are critical. Fortunately, the VA is well resourced in this domain, whereas many state health departments floundered in their response, causing unnecessary vaccination delays.⁹

2. Utility: Necessary But Insufficient

Most ethical approaches recognize to some extent that seeking good and minimizing harm is of value. However, a strictly utilitarian approach is insufficient to address the core values in conflict surrounding how best to allocate limited doses of COVID-19 vaccine. For example, some may argue that prioritizing the elderly or those in long-term care facilities like VA’s community living centers because they have the highest COVID-19 mortality rate produces less net benefit than prioritizing younger veterans with comorbidities or certain higher risk essential workers. There are 2 important points to make here.

First, the VHA vaccination plan balances utility with other ethical principles, namely, treating people with equal concern, and addressing health inequities, including a focus on justice and valuing the worth and dignity of each person. Rather than giving everyone an equal chance via lottery, the prioritization plan recognizes that some people have greater need or would stand to better mitigate viral contagion and preserve the essential workforce if they were vaccinated earlier. However, the principle of justice requires that efforts are made to treat like cases the same to avoid perceptions of bias, and to demonstrate respect for the dignity of each individual by way of promoting a fair vaccination process.

This requires transparency, consistency, and delivery of respectful and accurate communication. For example, the VA recognizes that lifetime exposure to social injustice produces health inequities that make Black, Hispanic, and Native American persons more susceptible to contracting COVID-19 and suffering serious or fatal illness. The approach to addressing this inequity is by giving priority to those with higher risk factors. Again, this is an example of blending and balancing ethical principles of utility and justice—that is, recognizing and remedying social injustice is of value both because it will help achieve better outcomes for persons of color and because it is inherently worthwhile to oppose injustice.

However, contrary to some news reports, the VHA approach does not allocate by race/ethnicity alone, as it does by age.^10,11 Doing so would present logistical challenges—for example, race/ethnicity is not an objective classification as is age, and reconciling individuals’ self-reports could create confusion or chaos that is antithetical to a fair, streamlined vaccination program. Putting veterans of color at the front of the vaccination line could backfire by amplifying worries that they are being exposed to vaccine that is not fully tested (a common contributor to vaccine hesitancy, particularly among communities of color familiar with prior exploitation and abuse in the name of science).

Discriminating based on race/ethnicity alone in the spirit of achieving equity would be precedent setting for the VA and would require a strong ethical justification. The decision to prioritize for vaccine based on risk factors strives to achieve this balance of equity and utility, as it encompasses VA staff and veterans of color by way of their status as essential workers or those with comorbidities. However, it is important to address race-based access barriers and vaccine hesitancy to satisfy the equity demands. This effort is underway (eg, engaging community champions and developing tailored educational resources to reach diverse communities).

In addition, pragmatic ethics recognizes that an overly granular, complicated allocation plan would be inefficient to implement. While it might be true that some veterans who are aged < 65 years may be at higher risk from COVID-19 than some elderly veterans, achieving the goals of fairness and transparency requires establishing a vaccine prioritization plan that is both ethically defensible and feasibly implementable (ie, achieves its goal of getting “needles into arms”). For example, veterans aged ≥ 65 years may be invited to schedule their vaccination before younger veterans, but any veteran may be accepted “on-call” for vaccine appointment no-shows via first-come, first-served or by lottery. Flexibility of response is crucial. This played out in adding flexibility around the decision to vaccinate veterans aged ≥ 75 years before those aged 65 to 74 years, after revisiting how this prioritization might affect feasibility and throughput and opting to allow the opportunity to include those aged ≥ 65 years.

There will no doubt be additional modifications to the vaccine allocation plan as more data become available. Since the danger of fueling suspicion and distrust is high (ie, that certain privileged people are jumping the line, as we heard reports of in some non-VA facilities).¹² There is an obvious ethical duty to explain why the chosen approach is ethically defensible. VA facility leaders should be able to answer how their approach achieves the goals of avoiding serious or fatal illness, reducing contagion, and preserving the essential workforce while ensuring a fair, respectful, evidence-based, and transparent process.

The Veterans Health Administration (VHA) COVID-19 vaccine allocation plan showcases several lessons for government and health care leaders in planning for future pandemics.¹ Many state governments—underresourced and overwhelmed with other COVID-19 demands—have struggled to get COVID-19 vaccines into the arms of their residents.² In contrast, the VHA was able to mobilize early to identify vaccine allocation guidelines and proactively prepare facilities to vaccinate VHA staff and veterans as soon as vaccines were approved under Emergency Use Authorization by the US Food and Drug Administration.^3,4

In August 2020, VHA formed a COVID-19 Vaccine Integrated Project Team, composed of 6 subgroups: communications, distribution, education, measurement, policy, prioritization, and vaccine safety. The National Center for Ethics in Health Care weighed in on the ethical justification for the developed vaccination risk stratification framework, which was informed by, but not identical to, that recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.⁵

Prioritizing who gets early access to a potentially life-saving vaccine weighs heavily on those leaders charged with making such decisions. The ethics of scarce resource allocation and triage protocols that may be necessary in a pandemic are often in tension with the patient-centered clinical ethics that health care practitioners (HCPs) encounter. HCPs require assistance in appreciating the ethical rationale for this shift in focus from the preference of the individual to the common good. The same is true for the risk stratification criteria required when there is not sufficient vaccine for all those who could benefit from immunization. Decisions must be transparent to ensure widespread acceptance and trust in the vaccination process. The ethical reasoning and values that are the basis for allocation criteria must be clearly, compassionately, and consistently communicated to the public, as outlined below. Ethical questions or concerns involve a conflict between core values: one of the central tasks of ethical analysis is to identify the available ethical options to resolve value conflicts. Several ethical frameworks for vaccine allocation are available—each balances and weighs the primary values of equity, dignity, beneficence, and utility slightly differently.⁶

For example, utilitarian ethics looks to produce the most good and avoid the most harm for the greatest number of people. Within this framework, there can be different notions of “good,” for example, saving the most lives, the most life years, the most quality life years, or the lives of those who have more life “innings” ahead. The approach of the US Department of Veterans Affairs (VA) focuses on saving the most lives in combination with avoiding suffering from serious illness, minimizing contagion, and preserving the essential workforce. Frameworks that give primacy to 1 notion of the good (ie, saving the most lives) may deprioritize other beneficial outcomes, such as allowing earlier return to work, school, and leisure activities that many find integral to human flourishing. Other ethical theories and principles may be used to support various allocation frameworks. For example, a pragmatic ethics approach might emphasize the importance of adapting the approach based on the evolving science and innovation surrounding COVID-19. Having more than 1 ethically defensible approach is common; the goal in ethics work is to be open to diversity of thought and reflect on the strength of one’s reasoning in resolving a core values conflict. We identify 2 central tenets of pandemic ethics that inform vaccine allocation.

1. Pandemic Ethics Requires Proactive Planning and Reevaluation of Continually Evolving Facts

There is an oft quoted saying among bioethicists: “Good ethics begins with good facts.” One obvious challenge during the COVID-19 pandemic has been the difficulty accessing up-to-date facts to inform decision making. If a main goal of a vaccination plan is to minimize the incidence of serious or fatal COVID-19 disease and contagion, myriad data points are needed to identify the best way to do this. For example, if 2 doses of the same vaccine are needed, this impacts the logistics of identifying, inviting, and scheduling eligible individuals and staffing vaccine clinics as well as ensuring that sufficient personal protective equipment and rescue equipment/medication are available to treat allergic reactions. If the adverse effects of vaccines lead to staff absenteeism or vaccine hesitancy, this needs to be factored into logistics.⁷ Tailored messaging is important to reduce appointment no-shows and vaccine nonadopters.⁸ Transportation to vaccination sites is a relevant factor: how a vaccine is stored, thawed, and reconstituted and its shelf life impacts whether it can be transported after thawing and what must be provided on site.

Consideration of the multifaceted factors influencing a successful vaccination campaign requires proactive planning and the readiness to pivot when new information is revealed. For example, vaccine appointment no-shows should be anticipated along with a fair process for allocating unused vaccine that would otherwise be wasted. This is an example of responsible stewardship of a scarce and life-saving resource. A higher than anticipated no-show rate would require revisiting a facility’s approach to ensuring that waste is avoided while the process is perceived to be fair and transparent. Ethical theories and principles cannot do all the work here; mindful attention to detail and proactive, informed planning are critical. Fortunately, the VA is well resourced in this domain, whereas many state health departments floundered in their response, causing unnecessary vaccination delays.⁹

2. Utility: Necessary But Insufficient

Most ethical approaches recognize to some extent that seeking good and minimizing harm is of value. However, a strictly utilitarian approach is insufficient to address the core values in conflict surrounding how best to allocate limited doses of COVID-19 vaccine. For example, some may argue that prioritizing the elderly or those in long-term care facilities like VA’s community living centers because they have the highest COVID-19 mortality rate produces less net benefit than prioritizing younger veterans with comorbidities or certain higher risk essential workers. There are 2 important points to make here.

First, the VHA vaccination plan balances utility with other ethical principles, namely, treating people with equal concern, and addressing health inequities, including a focus on justice and valuing the worth and dignity of each person. Rather than giving everyone an equal chance via lottery, the prioritization plan recognizes that some people have greater need or would stand to better mitigate viral contagion and preserve the essential workforce if they were vaccinated earlier. However, the principle of justice requires that efforts are made to treat like cases the same to avoid perceptions of bias, and to demonstrate respect for the dignity of each individual by way of promoting a fair vaccination process.

This requires transparency, consistency, and delivery of respectful and accurate communication. For example, the VA recognizes that lifetime exposure to social injustice produces health inequities that make Black, Hispanic, and Native American persons more susceptible to contracting COVID-19 and suffering serious or fatal illness. The approach to addressing this inequity is by giving priority to those with higher risk factors. Again, this is an example of blending and balancing ethical principles of utility and justice—that is, recognizing and remedying social injustice is of value both because it will help achieve better outcomes for persons of color and because it is inherently worthwhile to oppose injustice.

However, contrary to some news reports, the VHA approach does not allocate by race/ethnicity alone, as it does by age.^10,11 Doing so would present logistical challenges—for example, race/ethnicity is not an objective classification as is age, and reconciling individuals’ self-reports could create confusion or chaos that is antithetical to a fair, streamlined vaccination program. Putting veterans of color at the front of the vaccination line could backfire by amplifying worries that they are being exposed to vaccine that is not fully tested (a common contributor to vaccine hesitancy, particularly among communities of color familiar with prior exploitation and abuse in the name of science).

Discriminating based on race/ethnicity alone in the spirit of achieving equity would be precedent setting for the VA and would require a strong ethical justification. The decision to prioritize for vaccine based on risk factors strives to achieve this balance of equity and utility, as it encompasses VA staff and veterans of color by way of their status as essential workers or those with comorbidities. However, it is important to address race-based access barriers and vaccine hesitancy to satisfy the equity demands. This effort is underway (eg, engaging community champions and developing tailored educational resources to reach diverse communities).

In addition, pragmatic ethics recognizes that an overly granular, complicated allocation plan would be inefficient to implement. While it might be true that some veterans who are aged < 65 years may be at higher risk from COVID-19 than some elderly veterans, achieving the goals of fairness and transparency requires establishing a vaccine prioritization plan that is both ethically defensible and feasibly implementable (ie, achieves its goal of getting “needles into arms”). For example, veterans aged ≥ 65 years may be invited to schedule their vaccination before younger veterans, but any veteran may be accepted “on-call” for vaccine appointment no-shows via first-come, first-served or by lottery. Flexibility of response is crucial. This played out in adding flexibility around the decision to vaccinate veterans aged ≥ 75 years before those aged 65 to 74 years, after revisiting how this prioritization might affect feasibility and throughput and opting to allow the opportunity to include those aged ≥ 65 years.

There will no doubt be additional modifications to the vaccine allocation plan as more data become available. Since the danger of fueling suspicion and distrust is high (ie, that certain privileged people are jumping the line, as we heard reports of in some non-VA facilities).¹² There is an obvious ethical duty to explain why the chosen approach is ethically defensible. VA facility leaders should be able to answer how their approach achieves the goals of avoiding serious or fatal illness, reducing contagion, and preserving the essential workforce while ensuring a fair, respectful, evidence-based, and transparent process.

The Veterans Health Administration (VHA) COVID-19 vaccine allocation plan showcases several lessons for government and health care leaders in planning for future pandemics.¹ Many state governments—underresourced and overwhelmed with other COVID-19 demands—have struggled to get COVID-19 vaccines into the arms of their residents.² In contrast, the VHA was able to mobilize early to identify vaccine allocation guidelines and proactively prepare facilities to vaccinate VHA staff and veterans as soon as vaccines were approved under Emergency Use Authorization by the US Food and Drug Administration.^3,4

In August 2020, VHA formed a COVID-19 Vaccine Integrated Project Team, composed of 6 subgroups: communications, distribution, education, measurement, policy, prioritization, and vaccine safety. The National Center for Ethics in Health Care weighed in on the ethical justification for the developed vaccination risk stratification framework, which was informed by, but not identical to, that recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.⁵

Prioritizing who gets early access to a potentially life-saving vaccine weighs heavily on those leaders charged with making such decisions. The ethics of scarce resource allocation and triage protocols that may be necessary in a pandemic are often in tension with the patient-centered clinical ethics that health care practitioners (HCPs) encounter. HCPs require assistance in appreciating the ethical rationale for this shift in focus from the preference of the individual to the common good. The same is true for the risk stratification criteria required when there is not sufficient vaccine for all those who could benefit from immunization. Decisions must be transparent to ensure widespread acceptance and trust in the vaccination process. The ethical reasoning and values that are the basis for allocation criteria must be clearly, compassionately, and consistently communicated to the public, as outlined below. Ethical questions or concerns involve a conflict between core values: one of the central tasks of ethical analysis is to identify the available ethical options to resolve value conflicts. Several ethical frameworks for vaccine allocation are available—each balances and weighs the primary values of equity, dignity, beneficence, and utility slightly differently.⁶

For example, utilitarian ethics looks to produce the most good and avoid the most harm for the greatest number of people. Within this framework, there can be different notions of “good,” for example, saving the most lives, the most life years, the most quality life years, or the lives of those who have more life “innings” ahead. The approach of the US Department of Veterans Affairs (VA) focuses on saving the most lives in combination with avoiding suffering from serious illness, minimizing contagion, and preserving the essential workforce. Frameworks that give primacy to 1 notion of the good (ie, saving the most lives) may deprioritize other beneficial outcomes, such as allowing earlier return to work, school, and leisure activities that many find integral to human flourishing. Other ethical theories and principles may be used to support various allocation frameworks. For example, a pragmatic ethics approach might emphasize the importance of adapting the approach based on the evolving science and innovation surrounding COVID-19. Having more than 1 ethically defensible approach is common; the goal in ethics work is to be open to diversity of thought and reflect on the strength of one’s reasoning in resolving a core values conflict. We identify 2 central tenets of pandemic ethics that inform vaccine allocation.

1. Pandemic Ethics Requires Proactive Planning and Reevaluation of Continually Evolving Facts

There is an oft quoted saying among bioethicists: “Good ethics begins with good facts.” One obvious challenge during the COVID-19 pandemic has been the difficulty accessing up-to-date facts to inform decision making. If a main goal of a vaccination plan is to minimize the incidence of serious or fatal COVID-19 disease and contagion, myriad data points are needed to identify the best way to do this. For example, if 2 doses of the same vaccine are needed, this impacts the logistics of identifying, inviting, and scheduling eligible individuals and staffing vaccine clinics as well as ensuring that sufficient personal protective equipment and rescue equipment/medication are available to treat allergic reactions. If the adverse effects of vaccines lead to staff absenteeism or vaccine hesitancy, this needs to be factored into logistics.⁷ Tailored messaging is important to reduce appointment no-shows and vaccine nonadopters.⁸ Transportation to vaccination sites is a relevant factor: how a vaccine is stored, thawed, and reconstituted and its shelf life impacts whether it can be transported after thawing and what must be provided on site.

Consideration of the multifaceted factors influencing a successful vaccination campaign requires proactive planning and the readiness to pivot when new information is revealed. For example, vaccine appointment no-shows should be anticipated along with a fair process for allocating unused vaccine that would otherwise be wasted. This is an example of responsible stewardship of a scarce and life-saving resource. A higher than anticipated no-show rate would require revisiting a facility’s approach to ensuring that waste is avoided while the process is perceived to be fair and transparent. Ethical theories and principles cannot do all the work here; mindful attention to detail and proactive, informed planning are critical. Fortunately, the VA is well resourced in this domain, whereas many state health departments floundered in their response, causing unnecessary vaccination delays.⁹

2. Utility: Necessary But Insufficient

Most ethical approaches recognize to some extent that seeking good and minimizing harm is of value. However, a strictly utilitarian approach is insufficient to address the core values in conflict surrounding how best to allocate limited doses of COVID-19 vaccine. For example, some may argue that prioritizing the elderly or those in long-term care facilities like VA’s community living centers because they have the highest COVID-19 mortality rate produces less net benefit than prioritizing younger veterans with comorbidities or certain higher risk essential workers. There are 2 important points to make here.

First, the VHA vaccination plan balances utility with other ethical principles, namely, treating people with equal concern, and addressing health inequities, including a focus on justice and valuing the worth and dignity of each person. Rather than giving everyone an equal chance via lottery, the prioritization plan recognizes that some people have greater need or would stand to better mitigate viral contagion and preserve the essential workforce if they were vaccinated earlier. However, the principle of justice requires that efforts are made to treat like cases the same to avoid perceptions of bias, and to demonstrate respect for the dignity of each individual by way of promoting a fair vaccination process.

This requires transparency, consistency, and delivery of respectful and accurate communication. For example, the VA recognizes that lifetime exposure to social injustice produces health inequities that make Black, Hispanic, and Native American persons more susceptible to contracting COVID-19 and suffering serious or fatal illness. The approach to addressing this inequity is by giving priority to those with higher risk factors. Again, this is an example of blending and balancing ethical principles of utility and justice—that is, recognizing and remedying social injustice is of value both because it will help achieve better outcomes for persons of color and because it is inherently worthwhile to oppose injustice.

However, contrary to some news reports, the VHA approach does not allocate by race/ethnicity alone, as it does by age.^10,11 Doing so would present logistical challenges—for example, race/ethnicity is not an objective classification as is age, and reconciling individuals’ self-reports could create confusion or chaos that is antithetical to a fair, streamlined vaccination program. Putting veterans of color at the front of the vaccination line could backfire by amplifying worries that they are being exposed to vaccine that is not fully tested (a common contributor to vaccine hesitancy, particularly among communities of color familiar with prior exploitation and abuse in the name of science).

Discriminating based on race/ethnicity alone in the spirit of achieving equity would be precedent setting for the VA and would require a strong ethical justification. The decision to prioritize for vaccine based on risk factors strives to achieve this balance of equity and utility, as it encompasses VA staff and veterans of color by way of their status as essential workers or those with comorbidities. However, it is important to address race-based access barriers and vaccine hesitancy to satisfy the equity demands. This effort is underway (eg, engaging community champions and developing tailored educational resources to reach diverse communities).

In addition, pragmatic ethics recognizes that an overly granular, complicated allocation plan would be inefficient to implement. While it might be true that some veterans who are aged < 65 years may be at higher risk from COVID-19 than some elderly veterans, achieving the goals of fairness and transparency requires establishing a vaccine prioritization plan that is both ethically defensible and feasibly implementable (ie, achieves its goal of getting “needles into arms”). For example, veterans aged ≥ 65 years may be invited to schedule their vaccination before younger veterans, but any veteran may be accepted “on-call” for vaccine appointment no-shows via first-come, first-served or by lottery. Flexibility of response is crucial. This played out in adding flexibility around the decision to vaccinate veterans aged ≥ 75 years before those aged 65 to 74 years, after revisiting how this prioritization might affect feasibility and throughput and opting to allow the opportunity to include those aged ≥ 65 years.

There will no doubt be additional modifications to the vaccine allocation plan as more data become available. Since the danger of fueling suspicion and distrust is high (ie, that certain privileged people are jumping the line, as we heard reports of in some non-VA facilities).¹² There is an obvious ethical duty to explain why the chosen approach is ethically defensible. VA facility leaders should be able to answer how their approach achieves the goals of avoiding serious or fatal illness, reducing contagion, and preserving the essential workforce while ensuring a fair, respectful, evidence-based, and transparent process.

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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

Little has been known about children sick enough with COVID-19 to require intensive care because such patients are relatively few, but preliminary data analyzed from a nationwide registry indicate that they are more likely to be older, to be Black, and to have asthma.

Gastrointestinal distress is also more common in children with severe COVID-19, according to research by Sandeep Tripathi, MD. Dr. Tripathi, a pediatric intensivist and associate professor at the University of Illinois at Peoria, presented the findings on Feb. 3 at the Society for Critical Care Medicine (SCCM) 2021 Critical Care Congress.
 

Registry data gathered from 49 sites

Results from the SCCM’s VIRUS: COVID-19 Registry, which involved data from 49 sites, included 181 children admitted to an intensive care unit between February and July 2020. Those in the ICU were older than patients who did not receive care in the ICU (10 years vs. 3.67 years; P < .01) and were more likely to be Black (28.8% vs. 17.8%; P = .02).

More of the patients who required intensive care had preexisting conditions (58.2% vs. 44.3%; P = .01), the most common of which was asthma.

For both the ICU patients and the non-ICU group, the most common presenting symptom was fever.

Symptoms that were more common among children needing ICU care included nausea/vomiting (38.4% vs. 22.1%; P < .01), dyspnea (31.8% vs. 17.7%; P < .01), and abdominal pain (25.2% vs. 14.1%; P < .01).

Significantly higher proportions of ICU patients had multisystem inflammatory syndrome of childhood (MIS-C) (44.2% vs. 6.8%; P < .01) and acute kidney injury (9.34% vs. 1.7%; P < .01).

“The children who presented with MIS-C tended to be much sicker than children who present with just COVID,” Dr. Tripathi said in an interview.

In this analysis, among children in ICUs with COVID, the mortality rate was 4%, Dr. Tripathi said.

He said he hopes the information, which will be periodically published with updated data, will raise awareness of which children might be likely to experience progression to severe disease.

“The information may help physicians be more mindful of deterioration in those patients and be more aggressive in their management,” he said. When children are brought to the emergency department with the features this analysis highlights, he said, “physicians should have a low threshold for treating or admitting the patients.”

Another study that was presented on Feb. 3 in parallel with the registry study described patterns of illness among 68 children hospitalized with COVID-19 in a tertiary-care pediatric center.

In that analysis, Meghana Nadiger, MD, a critical care fellow with Nicklaus Children’s Hospital in Miami, found that all patients admitted to the pediatric ICU (n = 17) had either MIS-C or severe illness and COVID-19-related Kawasaki-like disease.

The investigators also found that the patients with serious illness were more commonly adolescents with elevated body mass index (73%). In this study, 83.8% of the hospitalized children were Hispanic. They also found that 88.8% of the children older than 2 years who had been hospitalized with COVID-19 were overweight or obese, with a BMI >25 kg/m².

Jerry Zimmerman, MD, PhD, SCCM’s immediate past president, said in an interview that he found it interesting that in the Nadiger study, “All of the children with severe illness had MIS-C as compared to adults, who typically are critically ill with severe acute respiratory distress syndrome.” Dr. Zimmerman was not involved in either study.

He said that although the high percentage of Hispanic patients in the hospitalized population may reflect the high percentage of Hispanic children in the Miami area, it may also reflect challenges of controlling the disease in the Hispanic community. Such challenges might include shortages of personal protective equipment, poorer access to health care, and difficulty in social distancing.

Dr. Zimmerman pointed out that obesity is an important risk factor for COVID-19 and that according to the Centers for Disease Control and Prevention, childhood obesity is much more common among Hispanics (25.8%) and non-Hispanic Blacks persons (22.0%) compared with non-Hispanic White persons (14.1%).

The VIRUS registry is funded in part by the Gordon and Betty Moore Foundation and Janssen Research and Development. Dr. Tripathi, Dr. Nadiger, and Dr. Zimmerman have disclosed no relevant financial relationships.

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

Little has been known about children sick enough with COVID-19 to require intensive care because such patients are relatively few, but preliminary data analyzed from a nationwide registry indicate that they are more likely to be older, to be Black, and to have asthma.

Gastrointestinal distress is also more common in children with severe COVID-19, according to research by Sandeep Tripathi, MD. Dr. Tripathi, a pediatric intensivist and associate professor at the University of Illinois at Peoria, presented the findings on Feb. 3 at the Society for Critical Care Medicine (SCCM) 2021 Critical Care Congress.
 

Registry data gathered from 49 sites

Results from the SCCM’s VIRUS: COVID-19 Registry, which involved data from 49 sites, included 181 children admitted to an intensive care unit between February and July 2020. Those in the ICU were older than patients who did not receive care in the ICU (10 years vs. 3.67 years; P < .01) and were more likely to be Black (28.8% vs. 17.8%; P = .02).

More of the patients who required intensive care had preexisting conditions (58.2% vs. 44.3%; P = .01), the most common of which was asthma.

For both the ICU patients and the non-ICU group, the most common presenting symptom was fever.

Symptoms that were more common among children needing ICU care included nausea/vomiting (38.4% vs. 22.1%; P < .01), dyspnea (31.8% vs. 17.7%; P < .01), and abdominal pain (25.2% vs. 14.1%; P < .01).

Significantly higher proportions of ICU patients had multisystem inflammatory syndrome of childhood (MIS-C) (44.2% vs. 6.8%; P < .01) and acute kidney injury (9.34% vs. 1.7%; P < .01).

“The children who presented with MIS-C tended to be much sicker than children who present with just COVID,” Dr. Tripathi said in an interview.

In this analysis, among children in ICUs with COVID, the mortality rate was 4%, Dr. Tripathi said.

He said he hopes the information, which will be periodically published with updated data, will raise awareness of which children might be likely to experience progression to severe disease.

“The information may help physicians be more mindful of deterioration in those patients and be more aggressive in their management,” he said. When children are brought to the emergency department with the features this analysis highlights, he said, “physicians should have a low threshold for treating or admitting the patients.”

Another study that was presented on Feb. 3 in parallel with the registry study described patterns of illness among 68 children hospitalized with COVID-19 in a tertiary-care pediatric center.

In that analysis, Meghana Nadiger, MD, a critical care fellow with Nicklaus Children’s Hospital in Miami, found that all patients admitted to the pediatric ICU (n = 17) had either MIS-C or severe illness and COVID-19-related Kawasaki-like disease.

The investigators also found that the patients with serious illness were more commonly adolescents with elevated body mass index (73%). In this study, 83.8% of the hospitalized children were Hispanic. They also found that 88.8% of the children older than 2 years who had been hospitalized with COVID-19 were overweight or obese, with a BMI >25 kg/m².

Jerry Zimmerman, MD, PhD, SCCM’s immediate past president, said in an interview that he found it interesting that in the Nadiger study, “All of the children with severe illness had MIS-C as compared to adults, who typically are critically ill with severe acute respiratory distress syndrome.” Dr. Zimmerman was not involved in either study.

He said that although the high percentage of Hispanic patients in the hospitalized population may reflect the high percentage of Hispanic children in the Miami area, it may also reflect challenges of controlling the disease in the Hispanic community. Such challenges might include shortages of personal protective equipment, poorer access to health care, and difficulty in social distancing.

Dr. Zimmerman pointed out that obesity is an important risk factor for COVID-19 and that according to the Centers for Disease Control and Prevention, childhood obesity is much more common among Hispanics (25.8%) and non-Hispanic Blacks persons (22.0%) compared with non-Hispanic White persons (14.1%).

The VIRUS registry is funded in part by the Gordon and Betty Moore Foundation and Janssen Research and Development. Dr. Tripathi, Dr. Nadiger, and Dr. Zimmerman have disclosed no relevant financial relationships.

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

Little has been known about children sick enough with COVID-19 to require intensive care because such patients are relatively few, but preliminary data analyzed from a nationwide registry indicate that they are more likely to be older, to be Black, and to have asthma.

Gastrointestinal distress is also more common in children with severe COVID-19, according to research by Sandeep Tripathi, MD. Dr. Tripathi, a pediatric intensivist and associate professor at the University of Illinois at Peoria, presented the findings on Feb. 3 at the Society for Critical Care Medicine (SCCM) 2021 Critical Care Congress.
 

Registry data gathered from 49 sites

Results from the SCCM’s VIRUS: COVID-19 Registry, which involved data from 49 sites, included 181 children admitted to an intensive care unit between February and July 2020. Those in the ICU were older than patients who did not receive care in the ICU (10 years vs. 3.67 years; P < .01) and were more likely to be Black (28.8% vs. 17.8%; P = .02).

More of the patients who required intensive care had preexisting conditions (58.2% vs. 44.3%; P = .01), the most common of which was asthma.

For both the ICU patients and the non-ICU group, the most common presenting symptom was fever.

Symptoms that were more common among children needing ICU care included nausea/vomiting (38.4% vs. 22.1%; P < .01), dyspnea (31.8% vs. 17.7%; P < .01), and abdominal pain (25.2% vs. 14.1%; P < .01).

Significantly higher proportions of ICU patients had multisystem inflammatory syndrome of childhood (MIS-C) (44.2% vs. 6.8%; P < .01) and acute kidney injury (9.34% vs. 1.7%; P < .01).

“The children who presented with MIS-C tended to be much sicker than children who present with just COVID,” Dr. Tripathi said in an interview.

In this analysis, among children in ICUs with COVID, the mortality rate was 4%, Dr. Tripathi said.

He said he hopes the information, which will be periodically published with updated data, will raise awareness of which children might be likely to experience progression to severe disease.

“The information may help physicians be more mindful of deterioration in those patients and be more aggressive in their management,” he said. When children are brought to the emergency department with the features this analysis highlights, he said, “physicians should have a low threshold for treating or admitting the patients.”

Another study that was presented on Feb. 3 in parallel with the registry study described patterns of illness among 68 children hospitalized with COVID-19 in a tertiary-care pediatric center.

In that analysis, Meghana Nadiger, MD, a critical care fellow with Nicklaus Children’s Hospital in Miami, found that all patients admitted to the pediatric ICU (n = 17) had either MIS-C or severe illness and COVID-19-related Kawasaki-like disease.

The investigators also found that the patients with serious illness were more commonly adolescents with elevated body mass index (73%). In this study, 83.8% of the hospitalized children were Hispanic. They also found that 88.8% of the children older than 2 years who had been hospitalized with COVID-19 were overweight or obese, with a BMI >25 kg/m².

Jerry Zimmerman, MD, PhD, SCCM’s immediate past president, said in an interview that he found it interesting that in the Nadiger study, “All of the children with severe illness had MIS-C as compared to adults, who typically are critically ill with severe acute respiratory distress syndrome.” Dr. Zimmerman was not involved in either study.

He said that although the high percentage of Hispanic patients in the hospitalized population may reflect the high percentage of Hispanic children in the Miami area, it may also reflect challenges of controlling the disease in the Hispanic community. Such challenges might include shortages of personal protective equipment, poorer access to health care, and difficulty in social distancing.

Dr. Zimmerman pointed out that obesity is an important risk factor for COVID-19 and that according to the Centers for Disease Control and Prevention, childhood obesity is much more common among Hispanics (25.8%) and non-Hispanic Blacks persons (22.0%) compared with non-Hispanic White persons (14.1%).

The VIRUS registry is funded in part by the Gordon and Betty Moore Foundation and Janssen Research and Development. Dr. Tripathi, Dr. Nadiger, and Dr. Zimmerman have disclosed no relevant financial relationships.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

The Food and Drug Administration has revised its emergency use authorization for COVID-19 convalescent plasma on the basis of the latest available data.

The revision states that only high-titer COVID-19 convalescent plasma can be used and only in hospitalized patients who are early in the disease course and those with impaired humoral immunity who cannot produce an adequate antibody response.

The revisions stem from new clinical trial data analyzed or reported since the original EUA was issued in August 2020. The original EUA did not have these restrictions.

“This and other changes to the EUA represent important updates to the use of convalescent plasma for the treatment of COVID-19 patients,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing the revisions.

“COVID-19 convalescent plasma used according to the revised EUA may have efficacy, and its known and potential benefits outweigh its known and potential risks,” the FDA said.

The agency said it revoked use of low-titer COVID-19 convalescent plasma on the basis of new data from clinical trials, including randomized, controlled trials, that have failed to demonstrate that low-titer convalescent plasma may be effective in the treatment of hospitalized patients with COVID-19.

The FDA’s updated fact sheet for health care providers on the use of COVID-19 convalescent plasma also notes that transfusion of COVID-19 convalescent plasma late in the disease course, following respiratory failure requiring intubation and mechanical ventilation, hasn’t been found to have clinical benefit.

The revised EUA also includes several additional tests that can be used to manufacture COVID-19 convalescent plasma.

“With this update, nine tests are now included in the EUA for testing plasma donations for anti-SARS-CoV-2 antibodies as a manufacturing step to determine suitability before release,” the FDA said.

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

The Food and Drug Administration has revised its emergency use authorization for COVID-19 convalescent plasma on the basis of the latest available data.

The revision states that only high-titer COVID-19 convalescent plasma can be used and only in hospitalized patients who are early in the disease course and those with impaired humoral immunity who cannot produce an adequate antibody response.

The revisions stem from new clinical trial data analyzed or reported since the original EUA was issued in August 2020. The original EUA did not have these restrictions.

“This and other changes to the EUA represent important updates to the use of convalescent plasma for the treatment of COVID-19 patients,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing the revisions.

“COVID-19 convalescent plasma used according to the revised EUA may have efficacy, and its known and potential benefits outweigh its known and potential risks,” the FDA said.

The agency said it revoked use of low-titer COVID-19 convalescent plasma on the basis of new data from clinical trials, including randomized, controlled trials, that have failed to demonstrate that low-titer convalescent plasma may be effective in the treatment of hospitalized patients with COVID-19.

The FDA’s updated fact sheet for health care providers on the use of COVID-19 convalescent plasma also notes that transfusion of COVID-19 convalescent plasma late in the disease course, following respiratory failure requiring intubation and mechanical ventilation, hasn’t been found to have clinical benefit.

The revised EUA also includes several additional tests that can be used to manufacture COVID-19 convalescent plasma.

“With this update, nine tests are now included in the EUA for testing plasma donations for anti-SARS-CoV-2 antibodies as a manufacturing step to determine suitability before release,” the FDA said.

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

The Food and Drug Administration has revised its emergency use authorization for COVID-19 convalescent plasma on the basis of the latest available data.

The revision states that only high-titer COVID-19 convalescent plasma can be used and only in hospitalized patients who are early in the disease course and those with impaired humoral immunity who cannot produce an adequate antibody response.

The revisions stem from new clinical trial data analyzed or reported since the original EUA was issued in August 2020. The original EUA did not have these restrictions.

“This and other changes to the EUA represent important updates to the use of convalescent plasma for the treatment of COVID-19 patients,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing the revisions.

“COVID-19 convalescent plasma used according to the revised EUA may have efficacy, and its known and potential benefits outweigh its known and potential risks,” the FDA said.

The agency said it revoked use of low-titer COVID-19 convalescent plasma on the basis of new data from clinical trials, including randomized, controlled trials, that have failed to demonstrate that low-titer convalescent plasma may be effective in the treatment of hospitalized patients with COVID-19.

The FDA’s updated fact sheet for health care providers on the use of COVID-19 convalescent plasma also notes that transfusion of COVID-19 convalescent plasma late in the disease course, following respiratory failure requiring intubation and mechanical ventilation, hasn’t been found to have clinical benefit.

The revised EUA also includes several additional tests that can be used to manufacture COVID-19 convalescent plasma.

“With this update, nine tests are now included in the EUA for testing plasma donations for anti-SARS-CoV-2 antibodies as a manufacturing step to determine suitability before release,” the FDA said.

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

As of January 10, 2021, a reported 4,041,396 first doses of Moderna’s COVID-19 vaccine had been administered in the US. Reports of 1,266 (0.03%) adverse effects (AEs) after receipt of the vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS), according to researchers from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Team and Food and Drug Administration in a Morbidity and Mortality Weekly Report early release.

The researchers screened VAERS reports that described suspected severe allergic reactions and anaphylaxis and collected information from medical records and outreach to healthcare facilities, providers, and recipients. They identified 108 reports for further review as possible severe allergic reaction, including anaphylaxis, a rare vaccination reaction. Ten cases were determined to be anaphylaxis—or a rate of 2.5 cases per million vaccine doses administered. Nine of the cases were people with a documented history of allergies or allergic reactions; 5 had a history of anaphylaxis.

The median interval from vaccine receipt to symptom onset was 7.5 minutes. Eight people had follow-up information available; all had recovered or were discharged. Of the case reports that were determined not to be anaphylaxis, 47 were assessed as nonanaphylactic allergic reactions and 47 were considered nonallergic adverse events. Four cases lacked enough information to be determined.

Based on those preliminary findings, it appears anaphylaxis is rare after the Moderna vaccination, but the researchers note that comparisons with other non–COVID-19 vaccines are constrained due to the limited information available this early in the vaccination program. They did cite an analysis of the Pfizer-BioNTech COVID-19 vaccine, also an mRNA vaccine, which estimated an initial rate of 11.1 cases per million doses after the first shot.

The researchers found a “strong female predominance” of anaphylaxis for both vaccines. All 10 anaphylaxis cases reported with the Moderna vaccine were in women. However, during the analytic period, 61% of first doses were given to women, vs 36% to men. Similarly, two thirds of first doses of the Pfizer-BioNTech vaccine were administered to women, and women were more affected.

Postvaccine COVID-19 Infections

But patients shouldn’t be too hasty to assume that symptoms after the vaccination are vaccine related, researchers at Israel’s Sheba Medical Center warn. The mere availability of a vaccine may lead to a certain laxity of precautions and a consequent rise in COVID-19 cases. “Thus, almost every physical complaint after vaccination poses a true diagnostic dilemma,” they point out, “as to whether an adverse reaction or a new COVID-19 infection is the cause.”

They studied 4,081 healthcare workers given the Pfizer-BioNTech vaccine. Of the vaccinated healthcare workers, 22 (0.54%) later had laboratory-confirmed COVID-19. Thirteen were tested because they had symptoms, usually an influenza-like illness that included fever, chills, cough, headache, myalgia, and sore throat. The median time between the first dose of vaccine and first symptoms was 3.5 days (one HCW had symptoms before immunization).

The vaccine, BNT162b2, is not likely to protect against clinical disease during the first days after receipt of the first dose, the researchers say. Efficacy was 52% a week after the first dose and positive COVID-19 cases were described among vaccinees even early after the second dose.

Clinicians should have a high level of suspicion of reported symptoms, the researchers advise, and avoid dismissing complaints as vaccine related until true infection is ruled out and the vaccine recipient is tested.

As of January 10, 2021, a reported 4,041,396 first doses of Moderna’s COVID-19 vaccine had been administered in the US. Reports of 1,266 (0.03%) adverse effects (AEs) after receipt of the vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS), according to researchers from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Team and Food and Drug Administration in a Morbidity and Mortality Weekly Report early release.

The researchers screened VAERS reports that described suspected severe allergic reactions and anaphylaxis and collected information from medical records and outreach to healthcare facilities, providers, and recipients. They identified 108 reports for further review as possible severe allergic reaction, including anaphylaxis, a rare vaccination reaction. Ten cases were determined to be anaphylaxis—or a rate of 2.5 cases per million vaccine doses administered. Nine of the cases were people with a documented history of allergies or allergic reactions; 5 had a history of anaphylaxis.

The median interval from vaccine receipt to symptom onset was 7.5 minutes. Eight people had follow-up information available; all had recovered or were discharged. Of the case reports that were determined not to be anaphylaxis, 47 were assessed as nonanaphylactic allergic reactions and 47 were considered nonallergic adverse events. Four cases lacked enough information to be determined.

Based on those preliminary findings, it appears anaphylaxis is rare after the Moderna vaccination, but the researchers note that comparisons with other non–COVID-19 vaccines are constrained due to the limited information available this early in the vaccination program. They did cite an analysis of the Pfizer-BioNTech COVID-19 vaccine, also an mRNA vaccine, which estimated an initial rate of 11.1 cases per million doses after the first shot.

The researchers found a “strong female predominance” of anaphylaxis for both vaccines. All 10 anaphylaxis cases reported with the Moderna vaccine were in women. However, during the analytic period, 61% of first doses were given to women, vs 36% to men. Similarly, two thirds of first doses of the Pfizer-BioNTech vaccine were administered to women, and women were more affected.

Postvaccine COVID-19 Infections

But patients shouldn’t be too hasty to assume that symptoms after the vaccination are vaccine related, researchers at Israel’s Sheba Medical Center warn. The mere availability of a vaccine may lead to a certain laxity of precautions and a consequent rise in COVID-19 cases. “Thus, almost every physical complaint after vaccination poses a true diagnostic dilemma,” they point out, “as to whether an adverse reaction or a new COVID-19 infection is the cause.”

They studied 4,081 healthcare workers given the Pfizer-BioNTech vaccine. Of the vaccinated healthcare workers, 22 (0.54%) later had laboratory-confirmed COVID-19. Thirteen were tested because they had symptoms, usually an influenza-like illness that included fever, chills, cough, headache, myalgia, and sore throat. The median time between the first dose of vaccine and first symptoms was 3.5 days (one HCW had symptoms before immunization).

The vaccine, BNT162b2, is not likely to protect against clinical disease during the first days after receipt of the first dose, the researchers say. Efficacy was 52% a week after the first dose and positive COVID-19 cases were described among vaccinees even early after the second dose.

Clinicians should have a high level of suspicion of reported symptoms, the researchers advise, and avoid dismissing complaints as vaccine related until true infection is ruled out and the vaccine recipient is tested.

As of January 10, 2021, a reported 4,041,396 first doses of Moderna’s COVID-19 vaccine had been administered in the US. Reports of 1,266 (0.03%) adverse effects (AEs) after receipt of the vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS), according to researchers from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Team and Food and Drug Administration in a Morbidity and Mortality Weekly Report early release.

The researchers screened VAERS reports that described suspected severe allergic reactions and anaphylaxis and collected information from medical records and outreach to healthcare facilities, providers, and recipients. They identified 108 reports for further review as possible severe allergic reaction, including anaphylaxis, a rare vaccination reaction. Ten cases were determined to be anaphylaxis—or a rate of 2.5 cases per million vaccine doses administered. Nine of the cases were people with a documented history of allergies or allergic reactions; 5 had a history of anaphylaxis.

The median interval from vaccine receipt to symptom onset was 7.5 minutes. Eight people had follow-up information available; all had recovered or were discharged. Of the case reports that were determined not to be anaphylaxis, 47 were assessed as nonanaphylactic allergic reactions and 47 were considered nonallergic adverse events. Four cases lacked enough information to be determined.

Based on those preliminary findings, it appears anaphylaxis is rare after the Moderna vaccination, but the researchers note that comparisons with other non–COVID-19 vaccines are constrained due to the limited information available this early in the vaccination program. They did cite an analysis of the Pfizer-BioNTech COVID-19 vaccine, also an mRNA vaccine, which estimated an initial rate of 11.1 cases per million doses after the first shot.

The researchers found a “strong female predominance” of anaphylaxis for both vaccines. All 10 anaphylaxis cases reported with the Moderna vaccine were in women. However, during the analytic period, 61% of first doses were given to women, vs 36% to men. Similarly, two thirds of first doses of the Pfizer-BioNTech vaccine were administered to women, and women were more affected.

Postvaccine COVID-19 Infections

But patients shouldn’t be too hasty to assume that symptoms after the vaccination are vaccine related, researchers at Israel’s Sheba Medical Center warn. The mere availability of a vaccine may lead to a certain laxity of precautions and a consequent rise in COVID-19 cases. “Thus, almost every physical complaint after vaccination poses a true diagnostic dilemma,” they point out, “as to whether an adverse reaction or a new COVID-19 infection is the cause.”

They studied 4,081 healthcare workers given the Pfizer-BioNTech vaccine. Of the vaccinated healthcare workers, 22 (0.54%) later had laboratory-confirmed COVID-19. Thirteen were tested because they had symptoms, usually an influenza-like illness that included fever, chills, cough, headache, myalgia, and sore throat. The median time between the first dose of vaccine and first symptoms was 3.5 days (one HCW had symptoms before immunization).

The vaccine, BNT162b2, is not likely to protect against clinical disease during the first days after receipt of the first dose, the researchers say. Efficacy was 52% a week after the first dose and positive COVID-19 cases were described among vaccinees even early after the second dose.

Clinicians should have a high level of suspicion of reported symptoms, the researchers advise, and avoid dismissing complaints as vaccine related until true infection is ruled out and the vaccine recipient is tested.

COVID-19 did not discriminate when it came to the impact it imposed on our hospitalist community. As the nomenclature moves away from the negative connotations of ‘burnout’ to ‘wellbeing,’ the pandemic has taught us something important about being intentional about our personal health: we must secure our own oxygen masks before helping others.

In February 2020, the Society of Hospital Medicine’s Wellbeing Taskforce efforts quickly changed focus from addressing general wellbeing, to wellbeing during COVID-19. Our Taskforce was commissioned by SHM’s Board with a new charge: Address immediate and ongoing needs of well-being and resiliency support for hospitalists during the COVID-19 pandemic. In this essay, I will discuss how our SHM Wellbeing Taskforce approached the overall topic of wellbeing for hospitalists during the COVID-19 pandemic, including some of our Taskforce group experiences.

The Taskforce started with a framework to aide in cultivating open and authentic conversations within hospital medicine groups. Creating spaces for honest sharing around how providers are doing is a crucial first step to reducing stigma, building mutual support within a group, and elevating issues of wellbeing to the level where structural change can take place. The Taskforce established two objectives for normalizing and mitigating stressors we face as hospitalists during the COVID-19 pandemic:

• Provide a framework for hospitalists to take their own emotional pulse
• Provide an approach to reduce stigma of hospitalists who are suffering from pandemic stress

While a more typical approach to fix stress and burnout is using formal institutional interventions, we used the value and insight provided by SHM’s 7 Drivers of Burnout in Hospital Medicine to help guide the creation of SHM resources in addressing the severe emotional strain being felt across the country by hospitalists. The 7 Drivers support the idea that the social role peers and hospital leaders can make a crucial difference in mitigating stress and burnout. Two examples of social support come to mind from the Wellbeing Taskforce experience:

• Participate in your meetings. One example comes from a member of our group who had underestimated the “healing power” that our group meetings had provided to his psyche. The simple act of participating in our Taskforce meeting and being in the presence of our group had provided such a positive impact that he was better able to face the “death and misery” in his unit with a smile on his face.
• Share what is stressful. The second example of social support comes from an hour of Zoom-based facilitation meetings between the SHM’s Wellbeing Taskforce members and Chapter Leaders in late October. During our Taskforce debrief after the meeting, we came to realize the enormous burden of grief our peers were carrying as one hospitalist had lost a group colleague the previous week due to suicide. Our member who led this meeting was moved – as were we – at how this had impacted his small team, and he was reminded he was not alone.

To form meaningful relationships that foster support, there needs to be a space where people can safely come together at times that initially might feel awkward. After taking steps toward your peers, these conversations can become normalized and contribute to meaningful relationships, providing the opportunity for healthy exchanges on vulnerable topics like emotional and psychological wellbeing. A printable guide for this specific purpose (“HM COVID-19 Check-In Guide for Self and Peers”) was designed to help hospitalists move into safe and supportive conversations with each other. While it is difficult to place a value on the importance these types of conversations have on individual wellbeing, it is known that the quality of a positive work environment where people feel supported can moderate stress, morale, and depression. In other words, hospitalist groups can positively contribute to their social environment during stressful times by sharing meaningful and difficult experiences with one another.

Second, the Taskforce created a social media campaign to provide a public social space for sharing hospitalists’ COVID-19 experiences. We believed that sharing collective experiences with the theme of #YouAreNotAlone and a complementary social media campaign, SHM Cares, on SHM’s social media channels, would further connect the national hospitalist community and provide a different communication pathway to decrease a sense of isolation. This idea came from the second social support idea mentioned earlier to share what is stressful with others in a safe space. We understood that some hospitalists would be more comfortable sharing publicly their comments, photos, and videos in achieving a sense of hospitalist unity.

Using our shared experiences, we identified three pillars for the final structure of the HM COVID-19 Check-In Guide for Self and Peers:

• Pillar 1. Recognize your issues. Recall our oxygen mask metaphor and this is what we mean by recognizing symptoms of new stressors (e.g., sleeplessness, irritability, forgetfulness).
• Pillar 2. Know what to say. A simple open-ended question about how the other person is working through the pandemic is an easy way to start a connection. We learned from a mental health perspective that it is unlikely that you could say anything to make a situation worse by offering a listening ear.
• Pillar 3. Check in with others. Listen to others without trying to fix the person or the situation. When appropriate, offer humorous reflections without diminishing the problem. Be a partner and commit to check in regularly with the other person.

Cultivating human connections outside of your immediate peer group can be valuable and offer additional perspective to stressful situations. For instance, one of my roles as a hospitalist administrator has been offering support by regularly listening as my physicians ‘talk out’ their day confidentially for as long as they needed. Offering open conversation in a safe and confidential way can have a healing effect. As one of my former hospitalists used to say, if issues are not addressed, they will “ooze out somewhere else.”

The HM COVID-19 Check-In Guide for Self and Peers and the SHM Cares social media campaign was the result of the Taskforce’s collective observations to help others normalize the feeling that ‘it’s OK not to be OK.’ Using the pandemic as context, the 7 Drivers of Hospitalist Burnout reminded us that the increased burnout issues we face will require continued attention past the pandemic. The value in cultivating human connections has never been more important. The SHM Wellbeing Taskforce is committed to provide continued resources. Checking in with others and listening to peers are all part of a personal wellbeing and resilience strategy. On behalf of the SHM Wellbeing Taskforce, we hope the information in this article will highlight the importance of continued attention to personal wellbeing during and after the pandemic.

Dr. Robinson received her PhD in organizational learning, performance and change from Colorado State University in 2019. Her dissertation topic was exploring hospitalist burnout, engagement, and social support. She is administrative director of inpatient medicine at St. Mary’s Medical Center in Grand Junction, Colo., a part of SCL Health. She has volunteered in numerous SHM committees, and currently serves on the SHM Wellbeing Taskforce.

COVID-19 did not discriminate when it came to the impact it imposed on our hospitalist community. As the nomenclature moves away from the negative connotations of ‘burnout’ to ‘wellbeing,’ the pandemic has taught us something important about being intentional about our personal health: we must secure our own oxygen masks before helping others.

In February 2020, the Society of Hospital Medicine’s Wellbeing Taskforce efforts quickly changed focus from addressing general wellbeing, to wellbeing during COVID-19. Our Taskforce was commissioned by SHM’s Board with a new charge: Address immediate and ongoing needs of well-being and resiliency support for hospitalists during the COVID-19 pandemic. In this essay, I will discuss how our SHM Wellbeing Taskforce approached the overall topic of wellbeing for hospitalists during the COVID-19 pandemic, including some of our Taskforce group experiences.

The Taskforce started with a framework to aide in cultivating open and authentic conversations within hospital medicine groups. Creating spaces for honest sharing around how providers are doing is a crucial first step to reducing stigma, building mutual support within a group, and elevating issues of wellbeing to the level where structural change can take place. The Taskforce established two objectives for normalizing and mitigating stressors we face as hospitalists during the COVID-19 pandemic:

• Provide a framework for hospitalists to take their own emotional pulse
• Provide an approach to reduce stigma of hospitalists who are suffering from pandemic stress

While a more typical approach to fix stress and burnout is using formal institutional interventions, we used the value and insight provided by SHM’s 7 Drivers of Burnout in Hospital Medicine to help guide the creation of SHM resources in addressing the severe emotional strain being felt across the country by hospitalists. The 7 Drivers support the idea that the social role peers and hospital leaders can make a crucial difference in mitigating stress and burnout. Two examples of social support come to mind from the Wellbeing Taskforce experience:

• Participate in your meetings. One example comes from a member of our group who had underestimated the “healing power” that our group meetings had provided to his psyche. The simple act of participating in our Taskforce meeting and being in the presence of our group had provided such a positive impact that he was better able to face the “death and misery” in his unit with a smile on his face.
• Share what is stressful. The second example of social support comes from an hour of Zoom-based facilitation meetings between the SHM’s Wellbeing Taskforce members and Chapter Leaders in late October. During our Taskforce debrief after the meeting, we came to realize the enormous burden of grief our peers were carrying as one hospitalist had lost a group colleague the previous week due to suicide. Our member who led this meeting was moved – as were we – at how this had impacted his small team, and he was reminded he was not alone.

To form meaningful relationships that foster support, there needs to be a space where people can safely come together at times that initially might feel awkward. After taking steps toward your peers, these conversations can become normalized and contribute to meaningful relationships, providing the opportunity for healthy exchanges on vulnerable topics like emotional and psychological wellbeing. A printable guide for this specific purpose (“HM COVID-19 Check-In Guide for Self and Peers”) was designed to help hospitalists move into safe and supportive conversations with each other. While it is difficult to place a value on the importance these types of conversations have on individual wellbeing, it is known that the quality of a positive work environment where people feel supported can moderate stress, morale, and depression. In other words, hospitalist groups can positively contribute to their social environment during stressful times by sharing meaningful and difficult experiences with one another.

Second, the Taskforce created a social media campaign to provide a public social space for sharing hospitalists’ COVID-19 experiences. We believed that sharing collective experiences with the theme of #YouAreNotAlone and a complementary social media campaign, SHM Cares, on SHM’s social media channels, would further connect the national hospitalist community and provide a different communication pathway to decrease a sense of isolation. This idea came from the second social support idea mentioned earlier to share what is stressful with others in a safe space. We understood that some hospitalists would be more comfortable sharing publicly their comments, photos, and videos in achieving a sense of hospitalist unity.

Using our shared experiences, we identified three pillars for the final structure of the HM COVID-19 Check-In Guide for Self and Peers:

• Pillar 1. Recognize your issues. Recall our oxygen mask metaphor and this is what we mean by recognizing symptoms of new stressors (e.g., sleeplessness, irritability, forgetfulness).
• Pillar 2. Know what to say. A simple open-ended question about how the other person is working through the pandemic is an easy way to start a connection. We learned from a mental health perspective that it is unlikely that you could say anything to make a situation worse by offering a listening ear.
• Pillar 3. Check in with others. Listen to others without trying to fix the person or the situation. When appropriate, offer humorous reflections without diminishing the problem. Be a partner and commit to check in regularly with the other person.

Cultivating human connections outside of your immediate peer group can be valuable and offer additional perspective to stressful situations. For instance, one of my roles as a hospitalist administrator has been offering support by regularly listening as my physicians ‘talk out’ their day confidentially for as long as they needed. Offering open conversation in a safe and confidential way can have a healing effect. As one of my former hospitalists used to say, if issues are not addressed, they will “ooze out somewhere else.”

The HM COVID-19 Check-In Guide for Self and Peers and the SHM Cares social media campaign was the result of the Taskforce’s collective observations to help others normalize the feeling that ‘it’s OK not to be OK.’ Using the pandemic as context, the 7 Drivers of Hospitalist Burnout reminded us that the increased burnout issues we face will require continued attention past the pandemic. The value in cultivating human connections has never been more important. The SHM Wellbeing Taskforce is committed to provide continued resources. Checking in with others and listening to peers are all part of a personal wellbeing and resilience strategy. On behalf of the SHM Wellbeing Taskforce, we hope the information in this article will highlight the importance of continued attention to personal wellbeing during and after the pandemic.

Dr. Robinson received her PhD in organizational learning, performance and change from Colorado State University in 2019. Her dissertation topic was exploring hospitalist burnout, engagement, and social support. She is administrative director of inpatient medicine at St. Mary’s Medical Center in Grand Junction, Colo., a part of SCL Health. She has volunteered in numerous SHM committees, and currently serves on the SHM Wellbeing Taskforce.

COVID-19 did not discriminate when it came to the impact it imposed on our hospitalist community. As the nomenclature moves away from the negative connotations of ‘burnout’ to ‘wellbeing,’ the pandemic has taught us something important about being intentional about our personal health: we must secure our own oxygen masks before helping others.

In February 2020, the Society of Hospital Medicine’s Wellbeing Taskforce efforts quickly changed focus from addressing general wellbeing, to wellbeing during COVID-19. Our Taskforce was commissioned by SHM’s Board with a new charge: Address immediate and ongoing needs of well-being and resiliency support for hospitalists during the COVID-19 pandemic. In this essay, I will discuss how our SHM Wellbeing Taskforce approached the overall topic of wellbeing for hospitalists during the COVID-19 pandemic, including some of our Taskforce group experiences.

The Taskforce started with a framework to aide in cultivating open and authentic conversations within hospital medicine groups. Creating spaces for honest sharing around how providers are doing is a crucial first step to reducing stigma, building mutual support within a group, and elevating issues of wellbeing to the level where structural change can take place. The Taskforce established two objectives for normalizing and mitigating stressors we face as hospitalists during the COVID-19 pandemic:

• Provide a framework for hospitalists to take their own emotional pulse
• Provide an approach to reduce stigma of hospitalists who are suffering from pandemic stress

While a more typical approach to fix stress and burnout is using formal institutional interventions, we used the value and insight provided by SHM’s 7 Drivers of Burnout in Hospital Medicine to help guide the creation of SHM resources in addressing the severe emotional strain being felt across the country by hospitalists. The 7 Drivers support the idea that the social role peers and hospital leaders can make a crucial difference in mitigating stress and burnout. Two examples of social support come to mind from the Wellbeing Taskforce experience:

• Participate in your meetings. One example comes from a member of our group who had underestimated the “healing power” that our group meetings had provided to his psyche. The simple act of participating in our Taskforce meeting and being in the presence of our group had provided such a positive impact that he was better able to face the “death and misery” in his unit with a smile on his face.
• Share what is stressful. The second example of social support comes from an hour of Zoom-based facilitation meetings between the SHM’s Wellbeing Taskforce members and Chapter Leaders in late October. During our Taskforce debrief after the meeting, we came to realize the enormous burden of grief our peers were carrying as one hospitalist had lost a group colleague the previous week due to suicide. Our member who led this meeting was moved – as were we – at how this had impacted his small team, and he was reminded he was not alone.

To form meaningful relationships that foster support, there needs to be a space where people can safely come together at times that initially might feel awkward. After taking steps toward your peers, these conversations can become normalized and contribute to meaningful relationships, providing the opportunity for healthy exchanges on vulnerable topics like emotional and psychological wellbeing. A printable guide for this specific purpose (“HM COVID-19 Check-In Guide for Self and Peers”) was designed to help hospitalists move into safe and supportive conversations with each other. While it is difficult to place a value on the importance these types of conversations have on individual wellbeing, it is known that the quality of a positive work environment where people feel supported can moderate stress, morale, and depression. In other words, hospitalist groups can positively contribute to their social environment during stressful times by sharing meaningful and difficult experiences with one another.

Second, the Taskforce created a social media campaign to provide a public social space for sharing hospitalists’ COVID-19 experiences. We believed that sharing collective experiences with the theme of #YouAreNotAlone and a complementary social media campaign, SHM Cares, on SHM’s social media channels, would further connect the national hospitalist community and provide a different communication pathway to decrease a sense of isolation. This idea came from the second social support idea mentioned earlier to share what is stressful with others in a safe space. We understood that some hospitalists would be more comfortable sharing publicly their comments, photos, and videos in achieving a sense of hospitalist unity.

Using our shared experiences, we identified three pillars for the final structure of the HM COVID-19 Check-In Guide for Self and Peers:

• Pillar 1. Recognize your issues. Recall our oxygen mask metaphor and this is what we mean by recognizing symptoms of new stressors (e.g., sleeplessness, irritability, forgetfulness).
• Pillar 2. Know what to say. A simple open-ended question about how the other person is working through the pandemic is an easy way to start a connection. We learned from a mental health perspective that it is unlikely that you could say anything to make a situation worse by offering a listening ear.
• Pillar 3. Check in with others. Listen to others without trying to fix the person or the situation. When appropriate, offer humorous reflections without diminishing the problem. Be a partner and commit to check in regularly with the other person.

Cultivating human connections outside of your immediate peer group can be valuable and offer additional perspective to stressful situations. For instance, one of my roles as a hospitalist administrator has been offering support by regularly listening as my physicians ‘talk out’ their day confidentially for as long as they needed. Offering open conversation in a safe and confidential way can have a healing effect. As one of my former hospitalists used to say, if issues are not addressed, they will “ooze out somewhere else.”

The HM COVID-19 Check-In Guide for Self and Peers and the SHM Cares social media campaign was the result of the Taskforce’s collective observations to help others normalize the feeling that ‘it’s OK not to be OK.’ Using the pandemic as context, the 7 Drivers of Hospitalist Burnout reminded us that the increased burnout issues we face will require continued attention past the pandemic. The value in cultivating human connections has never been more important. The SHM Wellbeing Taskforce is committed to provide continued resources. Checking in with others and listening to peers are all part of a personal wellbeing and resilience strategy. On behalf of the SHM Wellbeing Taskforce, we hope the information in this article will highlight the importance of continued attention to personal wellbeing during and after the pandemic.

Dr. Robinson received her PhD in organizational learning, performance and change from Colorado State University in 2019. Her dissertation topic was exploring hospitalist burnout, engagement, and social support. She is administrative director of inpatient medicine at St. Mary’s Medical Center in Grand Junction, Colo., a part of SCL Health. She has volunteered in numerous SHM committees, and currently serves on the SHM Wellbeing Taskforce.

Monoclonal antibodies (mAbs) to treat COVID-19 are in ample supply, but scant evidence on their effectiveness, paltry reimbursement, and a lack of a planned infrastructure to administer them has led to major underutilization of these potentially useful therapies, according to a new report from The National Academies of Sciences, Engineering, and Medicine.

The 35-page report described missed opportunities to work with states and hospitals to establish trust with clinicians and patients and to set up an infusion infrastructure to funnel patients to sites. Though the therapies still need more study, they should be an option for the right patient at the right time, said the National Academies experts in their report, Rapid Expert Consultation on Allocating COVID-19 Monoclonal Antibody Therapies and Other Novel Therapeutics.

“No potentially eligible patient should be left uninformed, and no eligible patient should be denied access, if there are doses available and the patient and doctor agree it is a reasonable course,” they concluded. The report also noted that underuse, and in particular underuse by members of vulnerable and underserved communities “raises concerns about exacerbating already dramatic health disparities.”

The federal government has spent $375 million on Eli Lilly’s bamlanivimab and $450 million on Regeneron’s casirivimab plus imdevimab cocktail, and agreed last month to spend as much as $2.6 billion more on up to 1.25 million additional doses.

Some 785,000 doses of the two therapeutics have been produced and about a half million have been distributed to states. But about three quarters have gone unused. The U.S. Department of Health & Human Services has launched an online treatment locater to try to spur interest in the therapies.

But the federal government hasn’t addressed some of the basic barriers to use of the monoclonals, said the National Academies experts.

“Lack of awareness, interest, and confidence in COVID-19 mAb therapies among patients and providers are major issues,” they said in the report. Patients who have tested positive might not want to travel to an infusion site, while others might not have access to health care or only seek such treatments when it’s too late. Some who are eligible might not have the time, resources, or transportation to go to a site and sit through a 2-hour treatment.

In addition, “the supply and availability of infusion centers and personnel was identified as a greater constraint than the supply of COVID-19 mAbs,” said the report.
 

Cost a big impediment

While the federal government has covered the cost of the therapies, hospitals and patients inevitably incur related costs.

“The fragmented payment system in the United States has not provided adequate support to cover the spectrum of costs associated with COVID-19 mAb therapies,” said the report. That is compounded by chronic underfunding and restrictions on federally qualified health centers for community health, the report said.

Patients may have to pay for testing, office visits, follow-up appointments, transportation to and from the infusion site, and potentially a copay for the administration of the drug.

While Medicare pays hospitals $309 per infusion, that might not be enough, especially if a hospital or other site had to build out a new infusion center, the report shows. For clinicians, the administrative payment under Medicare Part B does “not cover the total practice cost to furnish infusion services, resulting in a substantial cost-reimbursement disparity,” the report states.

In addition, there are no specific codes for observing patients during the 2-hour procedure.

“The established Medicare payment rate for furnishing COVID-19 mAb therapies does not cover the cost associated with coordinating care for those patients, nor does it justify the risk and opportunity costs associated with investing in infrastructure modifications to safely integrate COVID-19 patients into existing facilities or building temporary infusion capacity,” the report concluded.
 

More data needed

The U.S. Food and Drug Administration issued emergency-use authorizations (EUAs) for the two monoclonal therapies based on phase 2 trial data, and that leaves a lot of uncertainty, noted the National Academies.

In trials, both therapies reduced COVID-19-related hospitalizations and emergency room visits within 28 days after treatment among patients at high risk of progression, compared with those who received placebo.

But clinicians aren’t certain about who should use the monoclonals, said the report. The underuse has in turn led to trouble collecting data – either through ongoing trials or in starting new trials.

The National Academies recommended allocating the monoclonal antibodies in a way that would give rise to better data collection to inform clinicians. Payers could support the development of a core data platform or registry, or Medicare could develop pilot trials, said the report.

Lilly and UnitedHealth Group are collaborating on a study in high-risk Medicare patients, according to Reuters. Patients who test positive will be given bamlanivimab at home.

“Building infusion capacity and developing the evidence base about the impact of COVID-19 mAbs on clinical outcomes other than hospitalization, including mortality, are the most promising strategies for increasing effective utilization moving forward,” stated the National Academies report.

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

Monoclonal antibodies (mAbs) to treat COVID-19 are in ample supply, but scant evidence on their effectiveness, paltry reimbursement, and a lack of a planned infrastructure to administer them has led to major underutilization of these potentially useful therapies, according to a new report from The National Academies of Sciences, Engineering, and Medicine.

The 35-page report described missed opportunities to work with states and hospitals to establish trust with clinicians and patients and to set up an infusion infrastructure to funnel patients to sites. Though the therapies still need more study, they should be an option for the right patient at the right time, said the National Academies experts in their report, Rapid Expert Consultation on Allocating COVID-19 Monoclonal Antibody Therapies and Other Novel Therapeutics.

“No potentially eligible patient should be left uninformed, and no eligible patient should be denied access, if there are doses available and the patient and doctor agree it is a reasonable course,” they concluded. The report also noted that underuse, and in particular underuse by members of vulnerable and underserved communities “raises concerns about exacerbating already dramatic health disparities.”

The federal government has spent $375 million on Eli Lilly’s bamlanivimab and $450 million on Regeneron’s casirivimab plus imdevimab cocktail, and agreed last month to spend as much as $2.6 billion more on up to 1.25 million additional doses.

Some 785,000 doses of the two therapeutics have been produced and about a half million have been distributed to states. But about three quarters have gone unused. The U.S. Department of Health & Human Services has launched an online treatment locater to try to spur interest in the therapies.

But the federal government hasn’t addressed some of the basic barriers to use of the monoclonals, said the National Academies experts.

“Lack of awareness, interest, and confidence in COVID-19 mAb therapies among patients and providers are major issues,” they said in the report. Patients who have tested positive might not want to travel to an infusion site, while others might not have access to health care or only seek such treatments when it’s too late. Some who are eligible might not have the time, resources, or transportation to go to a site and sit through a 2-hour treatment.

In addition, “the supply and availability of infusion centers and personnel was identified as a greater constraint than the supply of COVID-19 mAbs,” said the report.
 

Cost a big impediment

While the federal government has covered the cost of the therapies, hospitals and patients inevitably incur related costs.

“The fragmented payment system in the United States has not provided adequate support to cover the spectrum of costs associated with COVID-19 mAb therapies,” said the report. That is compounded by chronic underfunding and restrictions on federally qualified health centers for community health, the report said.

Patients may have to pay for testing, office visits, follow-up appointments, transportation to and from the infusion site, and potentially a copay for the administration of the drug.

While Medicare pays hospitals $309 per infusion, that might not be enough, especially if a hospital or other site had to build out a new infusion center, the report shows. For clinicians, the administrative payment under Medicare Part B does “not cover the total practice cost to furnish infusion services, resulting in a substantial cost-reimbursement disparity,” the report states.

In addition, there are no specific codes for observing patients during the 2-hour procedure.

“The established Medicare payment rate for furnishing COVID-19 mAb therapies does not cover the cost associated with coordinating care for those patients, nor does it justify the risk and opportunity costs associated with investing in infrastructure modifications to safely integrate COVID-19 patients into existing facilities or building temporary infusion capacity,” the report concluded.
 

More data needed

The U.S. Food and Drug Administration issued emergency-use authorizations (EUAs) for the two monoclonal therapies based on phase 2 trial data, and that leaves a lot of uncertainty, noted the National Academies.

In trials, both therapies reduced COVID-19-related hospitalizations and emergency room visits within 28 days after treatment among patients at high risk of progression, compared with those who received placebo.

But clinicians aren’t certain about who should use the monoclonals, said the report. The underuse has in turn led to trouble collecting data – either through ongoing trials or in starting new trials.

The National Academies recommended allocating the monoclonal antibodies in a way that would give rise to better data collection to inform clinicians. Payers could support the development of a core data platform or registry, or Medicare could develop pilot trials, said the report.

Lilly and UnitedHealth Group are collaborating on a study in high-risk Medicare patients, according to Reuters. Patients who test positive will be given bamlanivimab at home.

“Building infusion capacity and developing the evidence base about the impact of COVID-19 mAbs on clinical outcomes other than hospitalization, including mortality, are the most promising strategies for increasing effective utilization moving forward,” stated the National Academies report.

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

Monoclonal antibodies (mAbs) to treat COVID-19 are in ample supply, but scant evidence on their effectiveness, paltry reimbursement, and a lack of a planned infrastructure to administer them has led to major underutilization of these potentially useful therapies, according to a new report from The National Academies of Sciences, Engineering, and Medicine.

The 35-page report described missed opportunities to work with states and hospitals to establish trust with clinicians and patients and to set up an infusion infrastructure to funnel patients to sites. Though the therapies still need more study, they should be an option for the right patient at the right time, said the National Academies experts in their report, Rapid Expert Consultation on Allocating COVID-19 Monoclonal Antibody Therapies and Other Novel Therapeutics.

“No potentially eligible patient should be left uninformed, and no eligible patient should be denied access, if there are doses available and the patient and doctor agree it is a reasonable course,” they concluded. The report also noted that underuse, and in particular underuse by members of vulnerable and underserved communities “raises concerns about exacerbating already dramatic health disparities.”

The federal government has spent $375 million on Eli Lilly’s bamlanivimab and $450 million on Regeneron’s casirivimab plus imdevimab cocktail, and agreed last month to spend as much as $2.6 billion more on up to 1.25 million additional doses.

Some 785,000 doses of the two therapeutics have been produced and about a half million have been distributed to states. But about three quarters have gone unused. The U.S. Department of Health & Human Services has launched an online treatment locater to try to spur interest in the therapies.

But the federal government hasn’t addressed some of the basic barriers to use of the monoclonals, said the National Academies experts.

“Lack of awareness, interest, and confidence in COVID-19 mAb therapies among patients and providers are major issues,” they said in the report. Patients who have tested positive might not want to travel to an infusion site, while others might not have access to health care or only seek such treatments when it’s too late. Some who are eligible might not have the time, resources, or transportation to go to a site and sit through a 2-hour treatment.

In addition, “the supply and availability of infusion centers and personnel was identified as a greater constraint than the supply of COVID-19 mAbs,” said the report.
 

Cost a big impediment

While the federal government has covered the cost of the therapies, hospitals and patients inevitably incur related costs.

“The fragmented payment system in the United States has not provided adequate support to cover the spectrum of costs associated with COVID-19 mAb therapies,” said the report. That is compounded by chronic underfunding and restrictions on federally qualified health centers for community health, the report said.

Patients may have to pay for testing, office visits, follow-up appointments, transportation to and from the infusion site, and potentially a copay for the administration of the drug.

While Medicare pays hospitals $309 per infusion, that might not be enough, especially if a hospital or other site had to build out a new infusion center, the report shows. For clinicians, the administrative payment under Medicare Part B does “not cover the total practice cost to furnish infusion services, resulting in a substantial cost-reimbursement disparity,” the report states.

In addition, there are no specific codes for observing patients during the 2-hour procedure.

“The established Medicare payment rate for furnishing COVID-19 mAb therapies does not cover the cost associated with coordinating care for those patients, nor does it justify the risk and opportunity costs associated with investing in infrastructure modifications to safely integrate COVID-19 patients into existing facilities or building temporary infusion capacity,” the report concluded.
 

More data needed

The U.S. Food and Drug Administration issued emergency-use authorizations (EUAs) for the two monoclonal therapies based on phase 2 trial data, and that leaves a lot of uncertainty, noted the National Academies.

In trials, both therapies reduced COVID-19-related hospitalizations and emergency room visits within 28 days after treatment among patients at high risk of progression, compared with those who received placebo.

But clinicians aren’t certain about who should use the monoclonals, said the report. The underuse has in turn led to trouble collecting data – either through ongoing trials or in starting new trials.

The National Academies recommended allocating the monoclonal antibodies in a way that would give rise to better data collection to inform clinicians. Payers could support the development of a core data platform or registry, or Medicare could develop pilot trials, said the report.

Lilly and UnitedHealth Group are collaborating on a study in high-risk Medicare patients, according to Reuters. Patients who test positive will be given bamlanivimab at home.

“Building infusion capacity and developing the evidence base about the impact of COVID-19 mAbs on clinical outcomes other than hospitalization, including mortality, are the most promising strategies for increasing effective utilization moving forward,” stated the National Academies report.

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

Among critically ill patients pulseless after planned withdrawal of life-sustaining therapies, cardiac activity restarted in 14% of cases, research shows.

Reassuringly, most resumption of heart activity happened in the first 1-2 minutes and most lasted 1 or 2 seconds.

“The reason we wanted to look at death determination specifically is we know that the stories persist about people coming back to life following death, and that’s not just in the public, it’s in the medical community as well,” lead author Sonny Dhanani, MD, of Children’s Hospital of Eastern Ontario, Ottawa, said in an interview.

“We thought that if we provided scientific evidence of whether this happened or not, we might dispel some myths and misunderstanding, which would hopefully promote organ donation.”

About 70% of organ donations occur after brain death, but an increasing number follow circulatory determination of death, he noted. Most protocols recommend 5 minutes of apnea and pulselessness by arterial catheter monitor before declaring death. But practices vary from 10 minutes in some European countries to 75 seconds in infant heart donors at one Colorado hospital.

Reports of patients recovering 10 minutes after pulselessness have raised concerns about the Lazarus phenomenon, or autoresuscitation, but are based in patients after cardiopulmonary resuscitation was terminated.

The present study, known as Death Prediction and Physiology after Removal of Therapy (DePParRT), enrolled patients at 20 intensive care sites in Canada, the Czech Republic, and the Netherlands, only if surrogate decision-makers agreed on withdrawal of life-sustaining measures without CPR and imminent death was anticipated.

As reported Jan. 28 in the New England Journal of Medicine, physicians observed resumption of circulation or cardiac activity prospectively in 1% of 631 patients based on bedside ECG, arterial pressure catheter monitors, palpated arterial pulse, breaths, or physical movements.

A retrospective review of data from 480 patients with complete ECG and arterial waveforms and at least 5 minutes of continuous waveform monitoring after pulselessness showed resumption of cardiac activity in 14% of patients.

The longest period of pulselessness before the heart showed signs of activity again was 4 minutes and 20 seconds. “So that was a reassuring number, because that’s within our 5-minute window that we currently use,” Dr. Dhanani said.

Importantly, “nobody woke up, nobody ended up being resuscitated, and all of these individuals died. And I think that’s going to be very helpful in this context,” he added.

In all, there were 77 cessations and resumptions in 67 of the 480 patients. The median duration of resumed cardiac activity was 3.9 seconds but, notably, ranged from 1 second to 13 minutes and 14 seconds.

“Though surprising, I think maybe not unreasonable,” observed Dr. Dhanani. “The heart is a very robust organ, and we maybe should anticipate these things happening, where at the end of life the heart may restart for minutes.”

In this situation, it’s important to wait the 13 minutes for the heart to stop again and then “wait another 5 minutes to make sure it doesn’t restart before determining death,” he said. “I think that’s where this study is going to now inform policy makers and guidelines, especially in the context of donations.”

The findings will be taken as strong support for the 5-minute window, said Robert Truog, MD, director of the Harvard Medical School Center for Bioethics and the Frances Glessner Lee Professor of Medical Ethics, Anaesthesia, and Pediatrics, Boston.

“I think it’s a safe point, I think people will refer to it, and it will be used to support the 5-minute window, and that’s probably reasonable,” he told this news organization. “Certainly, if it’s read in Europe it will cut the time from 10 minutes to 5 minutes, and that’s a good thing because 10 minutes is a very long time to wait.”

He noted that the 5-minute window provides reasonable assurance to the public and, with new technologies, permits most organs to be usable for donation after cardiac death. That said, there’s nothing magical about the number.

“In some ways I see this paper as providing interesting data but not actually providing an answer, because from the patient’s perspective and from the recipient’s perspective, waiting until the heart has made its last squeeze may not be the most relevant ethical question,” Dr. Truog said. “It may be, once we know this patient is not going to have return of cardiorespiratory function, is not going to wake up, that’s the point at which we ought to focus on organ preservation and organ retrieval, and that can be much sooner than 5 minutes.”

Dr. Dhanani and colleagues note that the generalizability of the results might be limited because patients without arterial pressure catheters were excluded, and 24% of enrolled patients could not be included in the retrospective waveform analysis owing to incomplete data.

“Our study definition of cardiac activity used an arbitrary threshold of pulse pressure (less than 5 mm Hg) that does not imply meaningful circulation,” they add. “This conservative consensus definition may have been partially responsible for the ostensibly high incidence (14%) of transient resumptions of cardiac activity identified through waveform adjudication.”

The study was supported by the Canadian Institutes for Health Research as part of the Canadian Donation and Transplantation Research Program, CHEO Research Institute, and Karel Pavlík Foundation. Dr. Dhanani has consulted for Canadian Blood Services. Dr. Truog reports no relevant conflicts of interest.

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

Among critically ill patients pulseless after planned withdrawal of life-sustaining therapies, cardiac activity restarted in 14% of cases, research shows.

Reassuringly, most resumption of heart activity happened in the first 1-2 minutes and most lasted 1 or 2 seconds.

“The reason we wanted to look at death determination specifically is we know that the stories persist about people coming back to life following death, and that’s not just in the public, it’s in the medical community as well,” lead author Sonny Dhanani, MD, of Children’s Hospital of Eastern Ontario, Ottawa, said in an interview.

“We thought that if we provided scientific evidence of whether this happened or not, we might dispel some myths and misunderstanding, which would hopefully promote organ donation.”

About 70% of organ donations occur after brain death, but an increasing number follow circulatory determination of death, he noted. Most protocols recommend 5 minutes of apnea and pulselessness by arterial catheter monitor before declaring death. But practices vary from 10 minutes in some European countries to 75 seconds in infant heart donors at one Colorado hospital.

Reports of patients recovering 10 minutes after pulselessness have raised concerns about the Lazarus phenomenon, or autoresuscitation, but are based in patients after cardiopulmonary resuscitation was terminated.

The present study, known as Death Prediction and Physiology after Removal of Therapy (DePParRT), enrolled patients at 20 intensive care sites in Canada, the Czech Republic, and the Netherlands, only if surrogate decision-makers agreed on withdrawal of life-sustaining measures without CPR and imminent death was anticipated.

As reported Jan. 28 in the New England Journal of Medicine, physicians observed resumption of circulation or cardiac activity prospectively in 1% of 631 patients based on bedside ECG, arterial pressure catheter monitors, palpated arterial pulse, breaths, or physical movements.

A retrospective review of data from 480 patients with complete ECG and arterial waveforms and at least 5 minutes of continuous waveform monitoring after pulselessness showed resumption of cardiac activity in 14% of patients.

The longest period of pulselessness before the heart showed signs of activity again was 4 minutes and 20 seconds. “So that was a reassuring number, because that’s within our 5-minute window that we currently use,” Dr. Dhanani said.

Importantly, “nobody woke up, nobody ended up being resuscitated, and all of these individuals died. And I think that’s going to be very helpful in this context,” he added.

In all, there were 77 cessations and resumptions in 67 of the 480 patients. The median duration of resumed cardiac activity was 3.9 seconds but, notably, ranged from 1 second to 13 minutes and 14 seconds.

“Though surprising, I think maybe not unreasonable,” observed Dr. Dhanani. “The heart is a very robust organ, and we maybe should anticipate these things happening, where at the end of life the heart may restart for minutes.”

In this situation, it’s important to wait the 13 minutes for the heart to stop again and then “wait another 5 minutes to make sure it doesn’t restart before determining death,” he said. “I think that’s where this study is going to now inform policy makers and guidelines, especially in the context of donations.”

The findings will be taken as strong support for the 5-minute window, said Robert Truog, MD, director of the Harvard Medical School Center for Bioethics and the Frances Glessner Lee Professor of Medical Ethics, Anaesthesia, and Pediatrics, Boston.

“I think it’s a safe point, I think people will refer to it, and it will be used to support the 5-minute window, and that’s probably reasonable,” he told this news organization. “Certainly, if it’s read in Europe it will cut the time from 10 minutes to 5 minutes, and that’s a good thing because 10 minutes is a very long time to wait.”

He noted that the 5-minute window provides reasonable assurance to the public and, with new technologies, permits most organs to be usable for donation after cardiac death. That said, there’s nothing magical about the number.

“In some ways I see this paper as providing interesting data but not actually providing an answer, because from the patient’s perspective and from the recipient’s perspective, waiting until the heart has made its last squeeze may not be the most relevant ethical question,” Dr. Truog said. “It may be, once we know this patient is not going to have return of cardiorespiratory function, is not going to wake up, that’s the point at which we ought to focus on organ preservation and organ retrieval, and that can be much sooner than 5 minutes.”

Dr. Dhanani and colleagues note that the generalizability of the results might be limited because patients without arterial pressure catheters were excluded, and 24% of enrolled patients could not be included in the retrospective waveform analysis owing to incomplete data.

“Our study definition of cardiac activity used an arbitrary threshold of pulse pressure (less than 5 mm Hg) that does not imply meaningful circulation,” they add. “This conservative consensus definition may have been partially responsible for the ostensibly high incidence (14%) of transient resumptions of cardiac activity identified through waveform adjudication.”

The study was supported by the Canadian Institutes for Health Research as part of the Canadian Donation and Transplantation Research Program, CHEO Research Institute, and Karel Pavlík Foundation. Dr. Dhanani has consulted for Canadian Blood Services. Dr. Truog reports no relevant conflicts of interest.

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

Among critically ill patients pulseless after planned withdrawal of life-sustaining therapies, cardiac activity restarted in 14% of cases, research shows.

Reassuringly, most resumption of heart activity happened in the first 1-2 minutes and most lasted 1 or 2 seconds.

“The reason we wanted to look at death determination specifically is we know that the stories persist about people coming back to life following death, and that’s not just in the public, it’s in the medical community as well,” lead author Sonny Dhanani, MD, of Children’s Hospital of Eastern Ontario, Ottawa, said in an interview.

“We thought that if we provided scientific evidence of whether this happened or not, we might dispel some myths and misunderstanding, which would hopefully promote organ donation.”

About 70% of organ donations occur after brain death, but an increasing number follow circulatory determination of death, he noted. Most protocols recommend 5 minutes of apnea and pulselessness by arterial catheter monitor before declaring death. But practices vary from 10 minutes in some European countries to 75 seconds in infant heart donors at one Colorado hospital.

Reports of patients recovering 10 minutes after pulselessness have raised concerns about the Lazarus phenomenon, or autoresuscitation, but are based in patients after cardiopulmonary resuscitation was terminated.

The present study, known as Death Prediction and Physiology after Removal of Therapy (DePParRT), enrolled patients at 20 intensive care sites in Canada, the Czech Republic, and the Netherlands, only if surrogate decision-makers agreed on withdrawal of life-sustaining measures without CPR and imminent death was anticipated.

As reported Jan. 28 in the New England Journal of Medicine, physicians observed resumption of circulation or cardiac activity prospectively in 1% of 631 patients based on bedside ECG, arterial pressure catheter monitors, palpated arterial pulse, breaths, or physical movements.

A retrospective review of data from 480 patients with complete ECG and arterial waveforms and at least 5 minutes of continuous waveform monitoring after pulselessness showed resumption of cardiac activity in 14% of patients.

The longest period of pulselessness before the heart showed signs of activity again was 4 minutes and 20 seconds. “So that was a reassuring number, because that’s within our 5-minute window that we currently use,” Dr. Dhanani said.

Importantly, “nobody woke up, nobody ended up being resuscitated, and all of these individuals died. And I think that’s going to be very helpful in this context,” he added.

In all, there were 77 cessations and resumptions in 67 of the 480 patients. The median duration of resumed cardiac activity was 3.9 seconds but, notably, ranged from 1 second to 13 minutes and 14 seconds.

“Though surprising, I think maybe not unreasonable,” observed Dr. Dhanani. “The heart is a very robust organ, and we maybe should anticipate these things happening, where at the end of life the heart may restart for minutes.”

In this situation, it’s important to wait the 13 minutes for the heart to stop again and then “wait another 5 minutes to make sure it doesn’t restart before determining death,” he said. “I think that’s where this study is going to now inform policy makers and guidelines, especially in the context of donations.”

The findings will be taken as strong support for the 5-minute window, said Robert Truog, MD, director of the Harvard Medical School Center for Bioethics and the Frances Glessner Lee Professor of Medical Ethics, Anaesthesia, and Pediatrics, Boston.

“I think it’s a safe point, I think people will refer to it, and it will be used to support the 5-minute window, and that’s probably reasonable,” he told this news organization. “Certainly, if it’s read in Europe it will cut the time from 10 minutes to 5 minutes, and that’s a good thing because 10 minutes is a very long time to wait.”

He noted that the 5-minute window provides reasonable assurance to the public and, with new technologies, permits most organs to be usable for donation after cardiac death. That said, there’s nothing magical about the number.

“In some ways I see this paper as providing interesting data but not actually providing an answer, because from the patient’s perspective and from the recipient’s perspective, waiting until the heart has made its last squeeze may not be the most relevant ethical question,” Dr. Truog said. “It may be, once we know this patient is not going to have return of cardiorespiratory function, is not going to wake up, that’s the point at which we ought to focus on organ preservation and organ retrieval, and that can be much sooner than 5 minutes.”

Dr. Dhanani and colleagues note that the generalizability of the results might be limited because patients without arterial pressure catheters were excluded, and 24% of enrolled patients could not be included in the retrospective waveform analysis owing to incomplete data.

“Our study definition of cardiac activity used an arbitrary threshold of pulse pressure (less than 5 mm Hg) that does not imply meaningful circulation,” they add. “This conservative consensus definition may have been partially responsible for the ostensibly high incidence (14%) of transient resumptions of cardiac activity identified through waveform adjudication.”

The study was supported by the Canadian Institutes for Health Research as part of the Canadian Donation and Transplantation Research Program, CHEO Research Institute, and Karel Pavlík Foundation. Dr. Dhanani has consulted for Canadian Blood Services. Dr. Truog reports no relevant conflicts of interest.

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

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

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

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

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

A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.

Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.

Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.

To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.

Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.

Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.

Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
 

A welcome option

The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.

“This is definitely – from what we can tell – a more effective method than the pill,” she said.

Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.

The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.

“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.

Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
 

One pregnancy

The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.

Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.

The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.

One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”

“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.

The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.

“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.

The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.

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