Stepping onto a busy coronavirus disease (COVID-19) unit for the first time can elicit trepidation for any medical provider. For a group of deployed pediatric residents at a New York City hospital in the spring of 2020, it was also the first time caring for adults since medical school. Imagine a pediatrician receiving this handoff: “77-year-old female with a history of diabetes, peripheral vascular disease, and COPD admitted with COVID-19 pneumonia, now intubated and proned with O2 saturations in the 80s. To do: DNR discussion.” General anxiety around COVID-19 was compounded by the discomfort of being thrust into adult medicine. But the doctoring instinct we have been honing throughout training kicked in, and we acted.

As the COVID-19 crisis escalated in New York City, it became evident that staff from other specialties would be essential to manage the surge of patients. Hospital administrators selected a group of trainees for deployment based on their clinical experiences and willingness to volunteer. Almost overnight, a group of senior pediatric residents became adult providers, honoring the oath we each took to “remain a member of society with special obligations to all . . . fellow human beings.”¹

This health crisis brought different clinical disciplines together like never before. Entire wings of the hospital were converted into new COVID-19–dedicated wards and intensive care units (ICUs), and teams were built to optimize providers’ skills and capabilities. For example, one third-year pediatric resident was grouped with an outpatient endocrinologist—who had not practiced inpatient medicine in a decade—and a medicine intern. Hospitalists provided crucial support and guidance to these ward teams of deployed providers who were eager and willing to work but often not very knowledgeable about inpatient adult medicine.² In new ad hoc COVID-19 ICUs housed in other ICUs, where most pediatric residents were deployed, critical care attendings and neurointensivists led teams that also included anesthesiology, radiology, and neurosurgery residents, as well as nurses and advanced practice providers trained in various subspecialties of adult medicine.

Although we wanted to help in any way we could, the prospect of entering this new world was incredibly daunting. We had not treated adults in several years, and during that time, our clinical experience with pediatric medicine greatly surpassed our adult training from medical school. We dug out materials on adult diseases, watched impromptu lectures on COVID-19 given by our critical care attendings, taught ourselves ventilator management in adults, and reviewed advanced cardiac life support (ACLS) protocols. But putting this all into practice was entirely different. Nothing can truly prepare you for arriving at the bedside of a hemodynamically unstable patient suffering from a virus that no one really understands.

When we arrived and introduced ourselves, we occasionally encountered surprise and curiosity from other providers. We felt that there was a perception that pediatricians do not often take care of critically ill or complex patients. Some of us were reluctant to disclose our specialty, lest it cloud perceptions of our capabilities. However, sick patients awaited us, so we got to work.

There was a steep learning curve over the first few days, from adjusting insulin for type 2 diabetes to troubleshooting renal replacement therapy issues. Accustomed to pediatric weight-based dosing, we were very anxious about ordering medications. The adult providers on our teams oriented us and helped us with many of these concerns. But the mystery of COVID-19 was a great equalizing force, leaving providers of every background with questions: Should we anticoagulate? How about steroids? Could this clinical change be another effect of the virus or a new infection?

We were pleasantly surprised that many aspects of our pediatric training proved beneficial in caring for adults. The focus on family-centered rounds and shared decision-making in pediatrics had imprinted on us the paramount importance of good communication. We were very cognizant of involving loved ones in discussions, now conducted by telephone or video call because infection-prevention guidelines precluded visitors. Family members were thankful for frequent updates, and as a result, largely embraced us as the doctors treating their loved ones. On one occasion, an internist, whose mother was a patient, was delighted to learn that the provider was a pediatric resident, saying, “I know you’ll take such good care of her.”

With the hospital inundated with sick adults, colleagues were grateful for our help. More so, they seemed appreciative of our compassion and ability to maintain a sense of humanity during the pandemonium of the pandemic despite feeling vulnerable, scared, and often powerless against COVID-19. In pediatrics, we do our best to truly engage with patients, from playing games with a 6-year-old with perforated appendicitis to holding and soothing a newborn in the neonatal ICU. We carried those skills over to the adult side. The team appreciated when a pediatric resident, with the help of an occupational therapist, used a letter board to communicate and receive assent for a tracheostomy from a nonsedated, intubated patient, directly answering the patient’s questions and addressing concerns rather than relying solely on a family member’s consent. And, though we had not previously led end-of-life discussions, we found that we were capable of doing so with the compassion instilled in us from our pediatric training. It had prepared us to face the universal challenge of communication in times of grief.

Besides grappling with our insecurity in treating adults, we, like all medical providers, had to balance our desire to provide care while keeping ourselves safe from COVID-19. To reduce our risk of exposure and preserve the dwindling supply of personal protective equipment (PPE), the flow of rounding, bedside care, and interventions was adapted to better cluster examinations, blood draws, and bedside tasks. Although efficient, this meant we did not enter rooms as frequently, creating an unfamiliar distance between provider and patient.³ We feared missing moments of clinical decompensation, and for pediatricians who value close patient contact, this made for a deeply uncomfortable reality.

We considered every plausible treatment for critically ill patients, sometimes unsure if they were beneficial or instead complicating the course further. Was lack of improvement a treatment failure or just the natural progression of this new illness? Unfortunately, most of the time, treatments were to no avail. Watching the respiratory, cardiovascular, renal, and neurologic devastation of COVID-19 on so many patients was horrifying. Seeing patients die without their loved ones beside them and at an alarmingly fast rate was simply crushing, as other trainees have similarly described.⁴ It was unlike anything we had ever experienced in pediatrics. Though we had begun to see a few pediatric COVID-19 patients in the hospital, their disease course was less severe. And, in the rare cases when pediatric patients die, they are almost invariably surrounded by family. One pediatric resident, who had never performed a single death examination before, did three in 1 week. It was emotionally trying, yet we had little time to mourn, as deathbeds were only briefly empty before the next gravely ill patients filled them.

Deployment took a toll on our bodies as well. We padded our faces to alleviate skin breakdown from 12-hour shifts spent entirely in N95 masks. We sanitized and washed our hands constantly, developing cracked skin and dermatitis, and showered meticulously after every shift. We isolated ourselves from our families and loved ones to protect them from the virus.

Despite these challenges, positive moments emerged. We worked with many wonderful colleagues from different disciplines we likely never would have met, let alone work alongside. We valued each other’s skills, talents, and knowledge. On an overnight shift in one of the ICUs, among the “ragtag team of deployees,” as one pediatric resident phrased it, each presented a topic from his or her respective specialty that might interest others. The pediatrician presented Kawasaki disease, as adult colleagues were beginning to ask questions about its cousin, the emerging multisystem inflammatory syndrome in children (MIS-C). This collegiality promoted a culture of collaboration and respect for other specialties that will hopefully continue.

A strong drive toward teamwork and shared responsibility flourished during deployment. No one was above any task. Residents and even fellows performed typical frontline tasks, such as ordering laboratory work and coordinating imaging. We all helped the proning team turn patients. Everyone shared insights, perspectives, and information gleaned from friends in different wards and hospitals and the ever-evolving literature. As we grappled with unpredictable disease courses, the traditional hierarchical roles of medicine—attending, fellow, resident—often blurred. We felt like we were all in this together.

Patient triumphs were celebrated. We danced with an 80-year-old patient admitted for almost 2 weeks when she was informed of her discharge and gave a standing ovation for a 91-year-old woman as she headed home. Music played over the hospital loudspeaker for every patient discharge. We also tried to create moments of lightheartedness. In the ICUs, we ate donated meals together and posed for pictures to express our gratitude to restaurants. Camaraderie blossomed during deployment.

Answering the call to help during the COVID-19 surge in New York City indelibly shaped our experiences as trainees and physicians. We will carry with us the lessons that we learned, both in the short term for the possible resurgence of cases and in the long term for ongoing patient care for the rest of our careers. For those residents who may be called upon next, the experience will be challenging, but rewarding. Each trainee has a foundation of knowledge, abilities, and instincts that will be useful, so trust in your training. Do not be afraid to ask questions or for help. You may be leaving your comfort zone, but you will not be alone, and families and other clinicians will be grateful to have you there. You are resilient, and you will make a difference.

The authors have nothing to disclose.

Stepping onto a busy coronavirus disease (COVID-19) unit for the first time can elicit trepidation for any medical provider. For a group of deployed pediatric residents at a New York City hospital in the spring of 2020, it was also the first time caring for adults since medical school. Imagine a pediatrician receiving this handoff: “77-year-old female with a history of diabetes, peripheral vascular disease, and COPD admitted with COVID-19 pneumonia, now intubated and proned with O2 saturations in the 80s. To do: DNR discussion.” General anxiety around COVID-19 was compounded by the discomfort of being thrust into adult medicine. But the doctoring instinct we have been honing throughout training kicked in, and we acted.

As the COVID-19 crisis escalated in New York City, it became evident that staff from other specialties would be essential to manage the surge of patients. Hospital administrators selected a group of trainees for deployment based on their clinical experiences and willingness to volunteer. Almost overnight, a group of senior pediatric residents became adult providers, honoring the oath we each took to “remain a member of society with special obligations to all . . . fellow human beings.”¹

This health crisis brought different clinical disciplines together like never before. Entire wings of the hospital were converted into new COVID-19–dedicated wards and intensive care units (ICUs), and teams were built to optimize providers’ skills and capabilities. For example, one third-year pediatric resident was grouped with an outpatient endocrinologist—who had not practiced inpatient medicine in a decade—and a medicine intern. Hospitalists provided crucial support and guidance to these ward teams of deployed providers who were eager and willing to work but often not very knowledgeable about inpatient adult medicine.² In new ad hoc COVID-19 ICUs housed in other ICUs, where most pediatric residents were deployed, critical care attendings and neurointensivists led teams that also included anesthesiology, radiology, and neurosurgery residents, as well as nurses and advanced practice providers trained in various subspecialties of adult medicine.

Although we wanted to help in any way we could, the prospect of entering this new world was incredibly daunting. We had not treated adults in several years, and during that time, our clinical experience with pediatric medicine greatly surpassed our adult training from medical school. We dug out materials on adult diseases, watched impromptu lectures on COVID-19 given by our critical care attendings, taught ourselves ventilator management in adults, and reviewed advanced cardiac life support (ACLS) protocols. But putting this all into practice was entirely different. Nothing can truly prepare you for arriving at the bedside of a hemodynamically unstable patient suffering from a virus that no one really understands.

When we arrived and introduced ourselves, we occasionally encountered surprise and curiosity from other providers. We felt that there was a perception that pediatricians do not often take care of critically ill or complex patients. Some of us were reluctant to disclose our specialty, lest it cloud perceptions of our capabilities. However, sick patients awaited us, so we got to work.

There was a steep learning curve over the first few days, from adjusting insulin for type 2 diabetes to troubleshooting renal replacement therapy issues. Accustomed to pediatric weight-based dosing, we were very anxious about ordering medications. The adult providers on our teams oriented us and helped us with many of these concerns. But the mystery of COVID-19 was a great equalizing force, leaving providers of every background with questions: Should we anticoagulate? How about steroids? Could this clinical change be another effect of the virus or a new infection?

We were pleasantly surprised that many aspects of our pediatric training proved beneficial in caring for adults. The focus on family-centered rounds and shared decision-making in pediatrics had imprinted on us the paramount importance of good communication. We were very cognizant of involving loved ones in discussions, now conducted by telephone or video call because infection-prevention guidelines precluded visitors. Family members were thankful for frequent updates, and as a result, largely embraced us as the doctors treating their loved ones. On one occasion, an internist, whose mother was a patient, was delighted to learn that the provider was a pediatric resident, saying, “I know you’ll take such good care of her.”

With the hospital inundated with sick adults, colleagues were grateful for our help. More so, they seemed appreciative of our compassion and ability to maintain a sense of humanity during the pandemonium of the pandemic despite feeling vulnerable, scared, and often powerless against COVID-19. In pediatrics, we do our best to truly engage with patients, from playing games with a 6-year-old with perforated appendicitis to holding and soothing a newborn in the neonatal ICU. We carried those skills over to the adult side. The team appreciated when a pediatric resident, with the help of an occupational therapist, used a letter board to communicate and receive assent for a tracheostomy from a nonsedated, intubated patient, directly answering the patient’s questions and addressing concerns rather than relying solely on a family member’s consent. And, though we had not previously led end-of-life discussions, we found that we were capable of doing so with the compassion instilled in us from our pediatric training. It had prepared us to face the universal challenge of communication in times of grief.

Besides grappling with our insecurity in treating adults, we, like all medical providers, had to balance our desire to provide care while keeping ourselves safe from COVID-19. To reduce our risk of exposure and preserve the dwindling supply of personal protective equipment (PPE), the flow of rounding, bedside care, and interventions was adapted to better cluster examinations, blood draws, and bedside tasks. Although efficient, this meant we did not enter rooms as frequently, creating an unfamiliar distance between provider and patient.³ We feared missing moments of clinical decompensation, and for pediatricians who value close patient contact, this made for a deeply uncomfortable reality.

We considered every plausible treatment for critically ill patients, sometimes unsure if they were beneficial or instead complicating the course further. Was lack of improvement a treatment failure or just the natural progression of this new illness? Unfortunately, most of the time, treatments were to no avail. Watching the respiratory, cardiovascular, renal, and neurologic devastation of COVID-19 on so many patients was horrifying. Seeing patients die without their loved ones beside them and at an alarmingly fast rate was simply crushing, as other trainees have similarly described.⁴ It was unlike anything we had ever experienced in pediatrics. Though we had begun to see a few pediatric COVID-19 patients in the hospital, their disease course was less severe. And, in the rare cases when pediatric patients die, they are almost invariably surrounded by family. One pediatric resident, who had never performed a single death examination before, did three in 1 week. It was emotionally trying, yet we had little time to mourn, as deathbeds were only briefly empty before the next gravely ill patients filled them.

Deployment took a toll on our bodies as well. We padded our faces to alleviate skin breakdown from 12-hour shifts spent entirely in N95 masks. We sanitized and washed our hands constantly, developing cracked skin and dermatitis, and showered meticulously after every shift. We isolated ourselves from our families and loved ones to protect them from the virus.

Despite these challenges, positive moments emerged. We worked with many wonderful colleagues from different disciplines we likely never would have met, let alone work alongside. We valued each other’s skills, talents, and knowledge. On an overnight shift in one of the ICUs, among the “ragtag team of deployees,” as one pediatric resident phrased it, each presented a topic from his or her respective specialty that might interest others. The pediatrician presented Kawasaki disease, as adult colleagues were beginning to ask questions about its cousin, the emerging multisystem inflammatory syndrome in children (MIS-C). This collegiality promoted a culture of collaboration and respect for other specialties that will hopefully continue.

A strong drive toward teamwork and shared responsibility flourished during deployment. No one was above any task. Residents and even fellows performed typical frontline tasks, such as ordering laboratory work and coordinating imaging. We all helped the proning team turn patients. Everyone shared insights, perspectives, and information gleaned from friends in different wards and hospitals and the ever-evolving literature. As we grappled with unpredictable disease courses, the traditional hierarchical roles of medicine—attending, fellow, resident—often blurred. We felt like we were all in this together.

Patient triumphs were celebrated. We danced with an 80-year-old patient admitted for almost 2 weeks when she was informed of her discharge and gave a standing ovation for a 91-year-old woman as she headed home. Music played over the hospital loudspeaker for every patient discharge. We also tried to create moments of lightheartedness. In the ICUs, we ate donated meals together and posed for pictures to express our gratitude to restaurants. Camaraderie blossomed during deployment.

Answering the call to help during the COVID-19 surge in New York City indelibly shaped our experiences as trainees and physicians. We will carry with us the lessons that we learned, both in the short term for the possible resurgence of cases and in the long term for ongoing patient care for the rest of our careers. For those residents who may be called upon next, the experience will be challenging, but rewarding. Each trainee has a foundation of knowledge, abilities, and instincts that will be useful, so trust in your training. Do not be afraid to ask questions or for help. You may be leaving your comfort zone, but you will not be alone, and families and other clinicians will be grateful to have you there. You are resilient, and you will make a difference.

The authors have nothing to disclose.

Stepping onto a busy coronavirus disease (COVID-19) unit for the first time can elicit trepidation for any medical provider. For a group of deployed pediatric residents at a New York City hospital in the spring of 2020, it was also the first time caring for adults since medical school. Imagine a pediatrician receiving this handoff: “77-year-old female with a history of diabetes, peripheral vascular disease, and COPD admitted with COVID-19 pneumonia, now intubated and proned with O2 saturations in the 80s. To do: DNR discussion.” General anxiety around COVID-19 was compounded by the discomfort of being thrust into adult medicine. But the doctoring instinct we have been honing throughout training kicked in, and we acted.

As the COVID-19 crisis escalated in New York City, it became evident that staff from other specialties would be essential to manage the surge of patients. Hospital administrators selected a group of trainees for deployment based on their clinical experiences and willingness to volunteer. Almost overnight, a group of senior pediatric residents became adult providers, honoring the oath we each took to “remain a member of society with special obligations to all . . . fellow human beings.”¹

This health crisis brought different clinical disciplines together like never before. Entire wings of the hospital were converted into new COVID-19–dedicated wards and intensive care units (ICUs), and teams were built to optimize providers’ skills and capabilities. For example, one third-year pediatric resident was grouped with an outpatient endocrinologist—who had not practiced inpatient medicine in a decade—and a medicine intern. Hospitalists provided crucial support and guidance to these ward teams of deployed providers who were eager and willing to work but often not very knowledgeable about inpatient adult medicine.² In new ad hoc COVID-19 ICUs housed in other ICUs, where most pediatric residents were deployed, critical care attendings and neurointensivists led teams that also included anesthesiology, radiology, and neurosurgery residents, as well as nurses and advanced practice providers trained in various subspecialties of adult medicine.

Although we wanted to help in any way we could, the prospect of entering this new world was incredibly daunting. We had not treated adults in several years, and during that time, our clinical experience with pediatric medicine greatly surpassed our adult training from medical school. We dug out materials on adult diseases, watched impromptu lectures on COVID-19 given by our critical care attendings, taught ourselves ventilator management in adults, and reviewed advanced cardiac life support (ACLS) protocols. But putting this all into practice was entirely different. Nothing can truly prepare you for arriving at the bedside of a hemodynamically unstable patient suffering from a virus that no one really understands.

When we arrived and introduced ourselves, we occasionally encountered surprise and curiosity from other providers. We felt that there was a perception that pediatricians do not often take care of critically ill or complex patients. Some of us were reluctant to disclose our specialty, lest it cloud perceptions of our capabilities. However, sick patients awaited us, so we got to work.

There was a steep learning curve over the first few days, from adjusting insulin for type 2 diabetes to troubleshooting renal replacement therapy issues. Accustomed to pediatric weight-based dosing, we were very anxious about ordering medications. The adult providers on our teams oriented us and helped us with many of these concerns. But the mystery of COVID-19 was a great equalizing force, leaving providers of every background with questions: Should we anticoagulate? How about steroids? Could this clinical change be another effect of the virus or a new infection?

We were pleasantly surprised that many aspects of our pediatric training proved beneficial in caring for adults. The focus on family-centered rounds and shared decision-making in pediatrics had imprinted on us the paramount importance of good communication. We were very cognizant of involving loved ones in discussions, now conducted by telephone or video call because infection-prevention guidelines precluded visitors. Family members were thankful for frequent updates, and as a result, largely embraced us as the doctors treating their loved ones. On one occasion, an internist, whose mother was a patient, was delighted to learn that the provider was a pediatric resident, saying, “I know you’ll take such good care of her.”

With the hospital inundated with sick adults, colleagues were grateful for our help. More so, they seemed appreciative of our compassion and ability to maintain a sense of humanity during the pandemonium of the pandemic despite feeling vulnerable, scared, and often powerless against COVID-19. In pediatrics, we do our best to truly engage with patients, from playing games with a 6-year-old with perforated appendicitis to holding and soothing a newborn in the neonatal ICU. We carried those skills over to the adult side. The team appreciated when a pediatric resident, with the help of an occupational therapist, used a letter board to communicate and receive assent for a tracheostomy from a nonsedated, intubated patient, directly answering the patient’s questions and addressing concerns rather than relying solely on a family member’s consent. And, though we had not previously led end-of-life discussions, we found that we were capable of doing so with the compassion instilled in us from our pediatric training. It had prepared us to face the universal challenge of communication in times of grief.

Besides grappling with our insecurity in treating adults, we, like all medical providers, had to balance our desire to provide care while keeping ourselves safe from COVID-19. To reduce our risk of exposure and preserve the dwindling supply of personal protective equipment (PPE), the flow of rounding, bedside care, and interventions was adapted to better cluster examinations, blood draws, and bedside tasks. Although efficient, this meant we did not enter rooms as frequently, creating an unfamiliar distance between provider and patient.³ We feared missing moments of clinical decompensation, and for pediatricians who value close patient contact, this made for a deeply uncomfortable reality.

We considered every plausible treatment for critically ill patients, sometimes unsure if they were beneficial or instead complicating the course further. Was lack of improvement a treatment failure or just the natural progression of this new illness? Unfortunately, most of the time, treatments were to no avail. Watching the respiratory, cardiovascular, renal, and neurologic devastation of COVID-19 on so many patients was horrifying. Seeing patients die without their loved ones beside them and at an alarmingly fast rate was simply crushing, as other trainees have similarly described.⁴ It was unlike anything we had ever experienced in pediatrics. Though we had begun to see a few pediatric COVID-19 patients in the hospital, their disease course was less severe. And, in the rare cases when pediatric patients die, they are almost invariably surrounded by family. One pediatric resident, who had never performed a single death examination before, did three in 1 week. It was emotionally trying, yet we had little time to mourn, as deathbeds were only briefly empty before the next gravely ill patients filled them.

Deployment took a toll on our bodies as well. We padded our faces to alleviate skin breakdown from 12-hour shifts spent entirely in N95 masks. We sanitized and washed our hands constantly, developing cracked skin and dermatitis, and showered meticulously after every shift. We isolated ourselves from our families and loved ones to protect them from the virus.

Despite these challenges, positive moments emerged. We worked with many wonderful colleagues from different disciplines we likely never would have met, let alone work alongside. We valued each other’s skills, talents, and knowledge. On an overnight shift in one of the ICUs, among the “ragtag team of deployees,” as one pediatric resident phrased it, each presented a topic from his or her respective specialty that might interest others. The pediatrician presented Kawasaki disease, as adult colleagues were beginning to ask questions about its cousin, the emerging multisystem inflammatory syndrome in children (MIS-C). This collegiality promoted a culture of collaboration and respect for other specialties that will hopefully continue.

A strong drive toward teamwork and shared responsibility flourished during deployment. No one was above any task. Residents and even fellows performed typical frontline tasks, such as ordering laboratory work and coordinating imaging. We all helped the proning team turn patients. Everyone shared insights, perspectives, and information gleaned from friends in different wards and hospitals and the ever-evolving literature. As we grappled with unpredictable disease courses, the traditional hierarchical roles of medicine—attending, fellow, resident—often blurred. We felt like we were all in this together.

Patient triumphs were celebrated. We danced with an 80-year-old patient admitted for almost 2 weeks when she was informed of her discharge and gave a standing ovation for a 91-year-old woman as she headed home. Music played over the hospital loudspeaker for every patient discharge. We also tried to create moments of lightheartedness. In the ICUs, we ate donated meals together and posed for pictures to express our gratitude to restaurants. Camaraderie blossomed during deployment.

Answering the call to help during the COVID-19 surge in New York City indelibly shaped our experiences as trainees and physicians. We will carry with us the lessons that we learned, both in the short term for the possible resurgence of cases and in the long term for ongoing patient care for the rest of our careers. For those residents who may be called upon next, the experience will be challenging, but rewarding. Each trainee has a foundation of knowledge, abilities, and instincts that will be useful, so trust in your training. Do not be afraid to ask questions or for help. You may be leaving your comfort zone, but you will not be alone, and families and other clinicians will be grateful to have you there. You are resilient, and you will make a difference.

The authors have nothing to disclose.

In 1957, Merton wrote that the primary aim of medical education should be “to provide [learners] with a professional identity so that [they] come to think, act, and feel like a physician.”¹ More than a half-century later, the Carnegie Foundation for the Advancement of Teaching echoed his sentiments in its landmark examination of the United States medical education system, which produced four key recommendations for curricular reform, including explicitly addressing professional identity formation (PIF).² PIF is a process by which a learner transforms into a physician with the values, dispositions, and aspirations of the physician community.³ It is now recognized as crucial to developing physicians who can deliver high-quality care.²

Major changes to the learning environment can impact PIF. For example, when the Accreditation Committee for Graduate Medical Education duty-hour restrictions were implemented in 2003, several educators were concerned that the changes may negatively affect resident PIF,⁴ whereas others saw an opportunity to refocus curricular efforts on PIF.⁵ Medical education is now in the midst of another radical change with the novel coronavirus disease 2019 (COVID-19) pandemic. Over the past several months, we have begun to understand the pandemic’s effects on medical education in terms of learner welfare, educational experiences/value, innovation, and assessment.^6-8 However, little has been published on the pandemic’s effect on PIF.⁹ We explore the impact of COVID-19 on physicians’ PIF and identify strategies to support PIF in physicians and other healthcare professionals during times of crisis.

PIF is dynamic and nonlinear, occurring at every level of the medical education hierarchy (medical student, resident, fellow, attending).¹⁰ Emphasis on PIF has grown in recent years as a response to the limitations of behavior-based educational frameworks such as competency-based medical education (CBME),³ which focuses on what the learner can “do.” PIF moves beyond “doing” to consider who the learner “is.”¹¹ PIF occurs at the individual level as learners progress through multiple distinct identity stages during their longitudinal formation^10,12-14 but also at the level of the collective. Socialization plays a crucial role; thus, PIF is heavily influenced by the environment, context, and other individuals.¹⁰

Medicine can be conceptualized as a community of practice, which is a sustaining network of individuals who share knowledge, beliefs, values, and experiences related to a common practice or purpose.^15,16 In a community of practice, learning is social, includes knowledge that is tacit to the community, and is situated within the context in which it will be applied. PIF involves learners moving from “legitimate peripheral participation,” whereby they are accepted as novice community members, to “full participation,” which involves gaining competence in relevant tasks and internalizing community principles to become full partners in the community.¹³ Critical to this process is exposure to socializing agents (eg, attendings, nurses, peers), observation of community interactions, experiential learning in the clinical environment, and access to role models.^10,16 Immersion in the clinical environment with other community members is thus crucial to PIF. This is especially important, as “medicine” is not truly a single community, but rather a “landscape of communities,” each with its own identity.¹⁷ Learners must therefore be immersed in many different clinical environments to experience the various communities within our field.

The pandemic is drastically altering the learning environment in medical education.⁸ Several institutions temporarily removed medical students from clinical rotations to reduce learner exposure and conserve personal protective equipment. Some residents were removed from nonessential clinical activities for similar reasons. Many attendings have been asked to work from home when not required to be present for clinical care duties. Common medical community activities, such as group meals and conferences, have been altered for physical distancing or simply canceled. Usual clinical care has rapidly evolved, with changes in rounding practices, a boon of telehealth, and cancellations of nonessential procedures. These necessary changes present constantly shifting grounds for anyone trying to integrate into a community and develop a professional identity.

Changes outside of the clinical learning environment are also affecting PIF. Social interactions, such as dinners and peer gatherings, occur via video conference or not at all. Most in-person contact happens with masks in place, physically distanced, and in smaller groups. Resident and student lounges are being modified to physically distance or reduce the number of occupants. There is often variable adherence, both intentional and unintentional, to physical distance and mask mandates, creating potential for confusion as learners try to internalize the values and norms of the medical community. Common professional rituals, such as white coat ceremonies, orientation events, and graduations, have been curtailed or canceled. Even experiences that are not commonly seen as social events but are important in the physician’s journey, such as the residency and fellowship application processes and standardized tests, are being transformed. These changes alter typical social patterns that are important in PIF and may adversely affect high-value social group interactions that serve as buffers against stressors during training.¹⁸

Finally, the pandemic has altered the timeline for many learners. Medical students at several institutions graduated early to join the workforce and help care for escalating numbers of patients during the pandemic.⁷ Some see the pandemic as a catalyst to move toward competency-based time-variable training, in which learners progress through training at variable rates depending on their individual performance and learning needs.¹⁹ These changes could shorten the amount of time some learners spend in a given role (eg, medical student, intern). In such situations, it is unclear whether a minimal maturational time is necessary for most learners to fully develop a professional identity.

In 2019, Cruess et al published general principles for supporting PIF,¹⁷ which have been used to support PIF during the COVID-19 pandemic.²⁰ In the Table, we describe these principles and provide examples of how to implement them in the context of the pandemic. We believe these principles are applicable for PIF in undergraduate medical education, graduate medical education, and faculty development programs. A common thread throughout the principles is that PIF is not a process that should be left to chance, but rather explicitly nurtured through systematic support and curricular initiatives.⁵ This may be challenging while the COVID-19 pandemic is sapping financial resources and requiring rapid changes to clinical systems, but given the central role PIF plays in physician development, it should be prioritized by educational leaders.

One of the final principles from Cruess et al is to create and maintain a welcoming community.¹⁷ This prompts questions such as: Is our community welcoming to everyone, where “everyone” really does mean everyone? Like other social structures, communities of practice tend to perpetuate existing power structures and inequities.¹⁷ It is no secret that medicine, like other professions, is riddled with inequities and bias based on factors such as race, gender, and socioeconomic status.^21-23 The COVID-19 pandemic is likely exacerbating these inequities, such as the adverse impacts that are specifically affecting women physicians, who take on a disproportionate share of the child care at home.²³ These biases impact not only the members of our professional community but also our patients, contributing to disparities in care and outcomes.

Physicians who have received inequitable treatment have laid bare the ways in which our communities of practice are failing them, and also outlined a better path on which to move forward.^21,23 In addition to recruitment practices that promote diversity, meaningful programs should be developed to support inclusion, equity (in recognition, support, compensation), retention, and advancement. The disruption caused by COVID-19 can be a catalyst for this change. By taking this moment of crisis to examine the values and norms of medicine and how we systematically perpetuate harmful inequities and biases, we have an opportunity to deliberately rebuild our community of practice in a manner that helps shape the next generation’s professional identities to be better than we have been. This should always be the aim of education.

In 1957, Merton wrote that the primary aim of medical education should be “to provide [learners] with a professional identity so that [they] come to think, act, and feel like a physician.”¹ More than a half-century later, the Carnegie Foundation for the Advancement of Teaching echoed his sentiments in its landmark examination of the United States medical education system, which produced four key recommendations for curricular reform, including explicitly addressing professional identity formation (PIF).² PIF is a process by which a learner transforms into a physician with the values, dispositions, and aspirations of the physician community.³ It is now recognized as crucial to developing physicians who can deliver high-quality care.²

Major changes to the learning environment can impact PIF. For example, when the Accreditation Committee for Graduate Medical Education duty-hour restrictions were implemented in 2003, several educators were concerned that the changes may negatively affect resident PIF,⁴ whereas others saw an opportunity to refocus curricular efforts on PIF.⁵ Medical education is now in the midst of another radical change with the novel coronavirus disease 2019 (COVID-19) pandemic. Over the past several months, we have begun to understand the pandemic’s effects on medical education in terms of learner welfare, educational experiences/value, innovation, and assessment.^6-8 However, little has been published on the pandemic’s effect on PIF.⁹ We explore the impact of COVID-19 on physicians’ PIF and identify strategies to support PIF in physicians and other healthcare professionals during times of crisis.

PIF is dynamic and nonlinear, occurring at every level of the medical education hierarchy (medical student, resident, fellow, attending).¹⁰ Emphasis on PIF has grown in recent years as a response to the limitations of behavior-based educational frameworks such as competency-based medical education (CBME),³ which focuses on what the learner can “do.” PIF moves beyond “doing” to consider who the learner “is.”¹¹ PIF occurs at the individual level as learners progress through multiple distinct identity stages during their longitudinal formation^10,12-14 but also at the level of the collective. Socialization plays a crucial role; thus, PIF is heavily influenced by the environment, context, and other individuals.¹⁰

Medicine can be conceptualized as a community of practice, which is a sustaining network of individuals who share knowledge, beliefs, values, and experiences related to a common practice or purpose.^15,16 In a community of practice, learning is social, includes knowledge that is tacit to the community, and is situated within the context in which it will be applied. PIF involves learners moving from “legitimate peripheral participation,” whereby they are accepted as novice community members, to “full participation,” which involves gaining competence in relevant tasks and internalizing community principles to become full partners in the community.¹³ Critical to this process is exposure to socializing agents (eg, attendings, nurses, peers), observation of community interactions, experiential learning in the clinical environment, and access to role models.^10,16 Immersion in the clinical environment with other community members is thus crucial to PIF. This is especially important, as “medicine” is not truly a single community, but rather a “landscape of communities,” each with its own identity.¹⁷ Learners must therefore be immersed in many different clinical environments to experience the various communities within our field.

The pandemic is drastically altering the learning environment in medical education.⁸ Several institutions temporarily removed medical students from clinical rotations to reduce learner exposure and conserve personal protective equipment. Some residents were removed from nonessential clinical activities for similar reasons. Many attendings have been asked to work from home when not required to be present for clinical care duties. Common medical community activities, such as group meals and conferences, have been altered for physical distancing or simply canceled. Usual clinical care has rapidly evolved, with changes in rounding practices, a boon of telehealth, and cancellations of nonessential procedures. These necessary changes present constantly shifting grounds for anyone trying to integrate into a community and develop a professional identity.

Changes outside of the clinical learning environment are also affecting PIF. Social interactions, such as dinners and peer gatherings, occur via video conference or not at all. Most in-person contact happens with masks in place, physically distanced, and in smaller groups. Resident and student lounges are being modified to physically distance or reduce the number of occupants. There is often variable adherence, both intentional and unintentional, to physical distance and mask mandates, creating potential for confusion as learners try to internalize the values and norms of the medical community. Common professional rituals, such as white coat ceremonies, orientation events, and graduations, have been curtailed or canceled. Even experiences that are not commonly seen as social events but are important in the physician’s journey, such as the residency and fellowship application processes and standardized tests, are being transformed. These changes alter typical social patterns that are important in PIF and may adversely affect high-value social group interactions that serve as buffers against stressors during training.¹⁸

Finally, the pandemic has altered the timeline for many learners. Medical students at several institutions graduated early to join the workforce and help care for escalating numbers of patients during the pandemic.⁷ Some see the pandemic as a catalyst to move toward competency-based time-variable training, in which learners progress through training at variable rates depending on their individual performance and learning needs.¹⁹ These changes could shorten the amount of time some learners spend in a given role (eg, medical student, intern). In such situations, it is unclear whether a minimal maturational time is necessary for most learners to fully develop a professional identity.

In 2019, Cruess et al published general principles for supporting PIF,¹⁷ which have been used to support PIF during the COVID-19 pandemic.²⁰ In the Table, we describe these principles and provide examples of how to implement them in the context of the pandemic. We believe these principles are applicable for PIF in undergraduate medical education, graduate medical education, and faculty development programs. A common thread throughout the principles is that PIF is not a process that should be left to chance, but rather explicitly nurtured through systematic support and curricular initiatives.⁵ This may be challenging while the COVID-19 pandemic is sapping financial resources and requiring rapid changes to clinical systems, but given the central role PIF plays in physician development, it should be prioritized by educational leaders.

One of the final principles from Cruess et al is to create and maintain a welcoming community.¹⁷ This prompts questions such as: Is our community welcoming to everyone, where “everyone” really does mean everyone? Like other social structures, communities of practice tend to perpetuate existing power structures and inequities.¹⁷ It is no secret that medicine, like other professions, is riddled with inequities and bias based on factors such as race, gender, and socioeconomic status.^21-23 The COVID-19 pandemic is likely exacerbating these inequities, such as the adverse impacts that are specifically affecting women physicians, who take on a disproportionate share of the child care at home.²³ These biases impact not only the members of our professional community but also our patients, contributing to disparities in care and outcomes.

Physicians who have received inequitable treatment have laid bare the ways in which our communities of practice are failing them, and also outlined a better path on which to move forward.^21,23 In addition to recruitment practices that promote diversity, meaningful programs should be developed to support inclusion, equity (in recognition, support, compensation), retention, and advancement. The disruption caused by COVID-19 can be a catalyst for this change. By taking this moment of crisis to examine the values and norms of medicine and how we systematically perpetuate harmful inequities and biases, we have an opportunity to deliberately rebuild our community of practice in a manner that helps shape the next generation’s professional identities to be better than we have been. This should always be the aim of education.

In 1957, Merton wrote that the primary aim of medical education should be “to provide [learners] with a professional identity so that [they] come to think, act, and feel like a physician.”¹ More than a half-century later, the Carnegie Foundation for the Advancement of Teaching echoed his sentiments in its landmark examination of the United States medical education system, which produced four key recommendations for curricular reform, including explicitly addressing professional identity formation (PIF).² PIF is a process by which a learner transforms into a physician with the values, dispositions, and aspirations of the physician community.³ It is now recognized as crucial to developing physicians who can deliver high-quality care.²

Major changes to the learning environment can impact PIF. For example, when the Accreditation Committee for Graduate Medical Education duty-hour restrictions were implemented in 2003, several educators were concerned that the changes may negatively affect resident PIF,⁴ whereas others saw an opportunity to refocus curricular efforts on PIF.⁵ Medical education is now in the midst of another radical change with the novel coronavirus disease 2019 (COVID-19) pandemic. Over the past several months, we have begun to understand the pandemic’s effects on medical education in terms of learner welfare, educational experiences/value, innovation, and assessment.^6-8 However, little has been published on the pandemic’s effect on PIF.⁹ We explore the impact of COVID-19 on physicians’ PIF and identify strategies to support PIF in physicians and other healthcare professionals during times of crisis.

PIF is dynamic and nonlinear, occurring at every level of the medical education hierarchy (medical student, resident, fellow, attending).¹⁰ Emphasis on PIF has grown in recent years as a response to the limitations of behavior-based educational frameworks such as competency-based medical education (CBME),³ which focuses on what the learner can “do.” PIF moves beyond “doing” to consider who the learner “is.”¹¹ PIF occurs at the individual level as learners progress through multiple distinct identity stages during their longitudinal formation^10,12-14 but also at the level of the collective. Socialization plays a crucial role; thus, PIF is heavily influenced by the environment, context, and other individuals.¹⁰

Medicine can be conceptualized as a community of practice, which is a sustaining network of individuals who share knowledge, beliefs, values, and experiences related to a common practice or purpose.^15,16 In a community of practice, learning is social, includes knowledge that is tacit to the community, and is situated within the context in which it will be applied. PIF involves learners moving from “legitimate peripheral participation,” whereby they are accepted as novice community members, to “full participation,” which involves gaining competence in relevant tasks and internalizing community principles to become full partners in the community.¹³ Critical to this process is exposure to socializing agents (eg, attendings, nurses, peers), observation of community interactions, experiential learning in the clinical environment, and access to role models.^10,16 Immersion in the clinical environment with other community members is thus crucial to PIF. This is especially important, as “medicine” is not truly a single community, but rather a “landscape of communities,” each with its own identity.¹⁷ Learners must therefore be immersed in many different clinical environments to experience the various communities within our field.

The pandemic is drastically altering the learning environment in medical education.⁸ Several institutions temporarily removed medical students from clinical rotations to reduce learner exposure and conserve personal protective equipment. Some residents were removed from nonessential clinical activities for similar reasons. Many attendings have been asked to work from home when not required to be present for clinical care duties. Common medical community activities, such as group meals and conferences, have been altered for physical distancing or simply canceled. Usual clinical care has rapidly evolved, with changes in rounding practices, a boon of telehealth, and cancellations of nonessential procedures. These necessary changes present constantly shifting grounds for anyone trying to integrate into a community and develop a professional identity.

Changes outside of the clinical learning environment are also affecting PIF. Social interactions, such as dinners and peer gatherings, occur via video conference or not at all. Most in-person contact happens with masks in place, physically distanced, and in smaller groups. Resident and student lounges are being modified to physically distance or reduce the number of occupants. There is often variable adherence, both intentional and unintentional, to physical distance and mask mandates, creating potential for confusion as learners try to internalize the values and norms of the medical community. Common professional rituals, such as white coat ceremonies, orientation events, and graduations, have been curtailed or canceled. Even experiences that are not commonly seen as social events but are important in the physician’s journey, such as the residency and fellowship application processes and standardized tests, are being transformed. These changes alter typical social patterns that are important in PIF and may adversely affect high-value social group interactions that serve as buffers against stressors during training.¹⁸

Finally, the pandemic has altered the timeline for many learners. Medical students at several institutions graduated early to join the workforce and help care for escalating numbers of patients during the pandemic.⁷ Some see the pandemic as a catalyst to move toward competency-based time-variable training, in which learners progress through training at variable rates depending on their individual performance and learning needs.¹⁹ These changes could shorten the amount of time some learners spend in a given role (eg, medical student, intern). In such situations, it is unclear whether a minimal maturational time is necessary for most learners to fully develop a professional identity.

In 2019, Cruess et al published general principles for supporting PIF,¹⁷ which have been used to support PIF during the COVID-19 pandemic.²⁰ In the Table, we describe these principles and provide examples of how to implement them in the context of the pandemic. We believe these principles are applicable for PIF in undergraduate medical education, graduate medical education, and faculty development programs. A common thread throughout the principles is that PIF is not a process that should be left to chance, but rather explicitly nurtured through systematic support and curricular initiatives.⁵ This may be challenging while the COVID-19 pandemic is sapping financial resources and requiring rapid changes to clinical systems, but given the central role PIF plays in physician development, it should be prioritized by educational leaders.

One of the final principles from Cruess et al is to create and maintain a welcoming community.¹⁷ This prompts questions such as: Is our community welcoming to everyone, where “everyone” really does mean everyone? Like other social structures, communities of practice tend to perpetuate existing power structures and inequities.¹⁷ It is no secret that medicine, like other professions, is riddled with inequities and bias based on factors such as race, gender, and socioeconomic status.^21-23 The COVID-19 pandemic is likely exacerbating these inequities, such as the adverse impacts that are specifically affecting women physicians, who take on a disproportionate share of the child care at home.²³ These biases impact not only the members of our professional community but also our patients, contributing to disparities in care and outcomes.

Physicians who have received inequitable treatment have laid bare the ways in which our communities of practice are failing them, and also outlined a better path on which to move forward.^21,23 In addition to recruitment practices that promote diversity, meaningful programs should be developed to support inclusion, equity (in recognition, support, compensation), retention, and advancement. The disruption caused by COVID-19 can be a catalyst for this change. By taking this moment of crisis to examine the values and norms of medicine and how we systematically perpetuate harmful inequities and biases, we have an opportunity to deliberately rebuild our community of practice in a manner that helps shape the next generation’s professional identities to be better than we have been. This should always be the aim of education.

Hospitalized patients receive care via a team-based approach. Because of frequent turnover and constant changes in team members, medical teams require rapid establishment of psychological safety. Psychological safety, or “being able to show and employ one’s self without fear of negative consequences of self-image, status or career,”¹ is at the core of successful team functioning. Google studied successful teams and found diverse personalities and skillsets work together most productively if they incorporate certain team dynamics; chief among these are focusing on shared values and psychological safety.² Times of acute crisis, especially those in which clinicians are working in unfamiliar settings and with new teams, increase the need for psychological safety. During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, many hospitals responded by forming ad hoc teams of non-hospitalist clinicians, including redeployed outpatient physicians and subspecialists.³ Because this situation was an acute crisis in which strangers (some new to the field) were suddenly working side by side, it was an excellent example of a moment that required rapid establishment of psychological safety. As subsequent waves of COVID-19 arrive, this will likely occur again. In this perspective, we identify strategies that help to establish psychological safety on medical teams, aiming to increase the effectiveness of teams caring for hospitalized patients, enhance leaders’ abilities to improve team function, and allow for delivery of high-quality patient care.

Psychological safety creates a nonthreatening team environment in which clinicians can ask questions and seek help with unfamiliar clinical scenarios. When psychological safety is present, the team dynamic encourages interpersonal risk-taking, improves learning, and increases the likelihood that team members will suggest new ideas.⁴ A culture of openness where people feel accepted and respected plays a vital role in helping people thrive in challenging and high-stakes work environments.⁵ In healthcare, team members who do not fear punishment for mistakes are more likely to disclose errors.⁶ Psychological safety has been associated with decreased anxiety in stressful situations, thereby freeing learners’ mental capacity to explore, innovate, and absorb new information.⁶

Through a thorough literature review, we identified strategies that can increase psychological safety on clinical teams. We focused on strategies applicable to acute crises, like COVID-19, when dynamic teams and uncertainty are rife. These strategies primarily focus on “team leaders,” generally the attendings or senior residents, who influence the team’s culture.

Discuss Mistakes

Creating a culture in which openly discussing mistakes is normalized and learning is fostered is especially important for healthcare providers redeployed to COVID-19 wards. Acknowledging errors can be challenging, especially in medicine, because success is often celebrated.⁷ Creating an environment where discussing mistakes in a nonjudgmental manner is the norm helps people disclose and learn from errors. By modeling fallibility, team leaders can create an environment where learning from mistakes seems less threatening.⁸ Leaders can say, “I may miss something. I encourage all members of the team to share what they know.”⁹

Provide Frequent Updates and Seek Feedback

Information and guidelines are changing frequently as we learn more about the novel coronavirus. The barrage of new information and periodic policy changes can be disconcerting. Leaders can dispel some of the team’s anxiety by providing a unified message that distills new information into clear and essential updates.⁹ They can reassure the team that updates will be provided frequently, be honest about what is known, and offer some predictability by providing updates at set times via consistent forms of communication during times of crisis. They can show empathy by inquiring about individual worries and responding to concerns about changes that are being made in response to COVID-19.¹⁰ Leaders should routinely seek feedback. They can ask, “How are things going for you? What can we improve? What should we do differently? How can I make you feel more comfortable or help you learn more effectively?” Inviting input communicates that everyone’s opinion is respected and creates a climate where everyone feels comfortable asking questions or respectfully expressing diverging opinions.⁹

Foster Creativity and Seek New Ideas

Curiosity and creativity are associated with better group outcomes.¹¹ Curiosity, or the motivation to learn and seek new ideas, improves individual and group dynamics by stimulating better job performance, inspiring leaders to discover more creative solutions, and encouraging employees to develop more trusting relationships, which makes them less likely to stereotype coworkers and patients as they ask questions and learn about others.¹² People who approach situations with a more creative perspective are less likely to react defensively. Curious people tend to try to learn about and understand different points of view.¹³ For example, if an order is not placed for a patient, a curious team leader might think about why—was there disagreement on the order, confusion on how to place it, or was it inadvertently forgotten?—and be able help avoid similar scenarios in the future. This ability to see things from another person’s point of view helps individuals with diverse clinical, social, and ethnic backgrounds function as a harmonious team. An attitude of curiosity and interest in learning about what each person can contribute based on their unique training and personality will help well-functioning teams form in response to COVID-19. Openness to new ideas allows for more innovative solutions, which are important in times of crisis. To promote curiosity, team members should discuss differences and varied opinions openly. This open dialogue provides individuals opportunities to learn from each other.⁵

Build Connection and Trust

A culture of trust—the belief that others will act for the good of the team—helps create psychological safety.¹⁰ Leaders can build trust by making expectations clear, being consistent, being inclusive, and modeling behaviors they wish to encourage.⁶ Predictability reduces anxiety and promotes psychological safety.⁹ Defining goals and expectations helps people relax, ask questions, and focus on learning.¹⁴ In times of crisis, leaders can tell teams what changes to expect, spell out new priorities, and assign specific tasks to give people a way to contribute.¹⁵

Activities that create connection also build trust, enhancing the team’s sense of psychological safety. Shared experiences foster connections.² Leaders can encourage team bonding by setting aside time to share stories and coping strategies.¹⁰ Chief residents in the early days of the pandemic found defining social distancing only as physical separation and focusing on emotional bonds helped maintain a sense of community. Debriefing about emotional patient encounters and discussing interesting clinical cases during video calls were ways to implement this strategy.¹⁰ Team members feel connected to each other and dedicated to their work if they focus on the meaning of the work to them, as well as its impact on society.² This shared belief that what they are doing matters to their community helps bond them.² Currently, the shared experience of treating a novel illness during the COVID-19 pandemic and the common goal of patient well-being unites healthcare providers across the globe. Leaders can create solidarity by emphasizing the shared identity of fighting COVID-19 and reminding teams of the impact of their work. Leaders can say, “Remember, we are here to improve patients’ health and form emotional bonds with people and their families.” These reminders have been shown to promote psychological safety and connection.¹⁶

Make Team Members Feel Valued

As many healthcare providers work harder or in unfamiliar environments during this pandemic, recognition of their efforts by leaders can be especially motivating and meaningful. When individuals on a team feel their work is valued, it helps create a sense of psychological safety.¹⁷ Employees feel valued when they believe their leaders care, they are in socially supportive environments, and are given resources for professional growth.¹⁷ Diversity and inclusion are also associated with feeling valued.¹⁷ During the height of the initial COVID-19 surge at our hospital, the chief of the Department of Medicine regularly sent messages and photographs of trainees and faculty, showing teams coming together during these unprecedented times. This boosted morale and created comradery and is an excellent example of a leader modeling inclusion.

Gratitude strengthens relationships and motivates people, especially when its expression is thoughtful and unique to individuals.¹⁸ Sincere compliments, acknowledgement of hard work, inclusiveness, and gratitude all contribute to team members feeling at ease and are key to leading, especially in times of crisis.¹⁷ Leaders can provide motivation by affirming the team’s ability to work together. Leaders can say, “I believe in each and every one of your capabilities—and I believe even more so in our joint capabilities. We can do this together.”¹⁹

Psychological safety is a powerful predictor of team performance, increased engagement, and satisfaction. It is critical for creating teams that can deal with uncertainty in high-risk situations, promoting a culture that is safe to acknowledge mistakes and take chances, which is important for optimal team functioning. Crises like the COVID-19 pandemic emphasize the need for psychologically safe team climates to promote learning, safe patient care, and team support. Hospitalists often care for patients when they are at their most vulnerable. Respecting and connecting with patients, through good and efficient teamwork, is important to providing effective care. The strategies suggested in this article strive to help hospitalists create a respectful culture to strengthen relationships with patients and colleagues in order to create an inclusive environment in times of crisis.

Hospitalized patients receive care via a team-based approach. Because of frequent turnover and constant changes in team members, medical teams require rapid establishment of psychological safety. Psychological safety, or “being able to show and employ one’s self without fear of negative consequences of self-image, status or career,”¹ is at the core of successful team functioning. Google studied successful teams and found diverse personalities and skillsets work together most productively if they incorporate certain team dynamics; chief among these are focusing on shared values and psychological safety.² Times of acute crisis, especially those in which clinicians are working in unfamiliar settings and with new teams, increase the need for psychological safety. During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, many hospitals responded by forming ad hoc teams of non-hospitalist clinicians, including redeployed outpatient physicians and subspecialists.³ Because this situation was an acute crisis in which strangers (some new to the field) were suddenly working side by side, it was an excellent example of a moment that required rapid establishment of psychological safety. As subsequent waves of COVID-19 arrive, this will likely occur again. In this perspective, we identify strategies that help to establish psychological safety on medical teams, aiming to increase the effectiveness of teams caring for hospitalized patients, enhance leaders’ abilities to improve team function, and allow for delivery of high-quality patient care.

Psychological safety creates a nonthreatening team environment in which clinicians can ask questions and seek help with unfamiliar clinical scenarios. When psychological safety is present, the team dynamic encourages interpersonal risk-taking, improves learning, and increases the likelihood that team members will suggest new ideas.⁴ A culture of openness where people feel accepted and respected plays a vital role in helping people thrive in challenging and high-stakes work environments.⁵ In healthcare, team members who do not fear punishment for mistakes are more likely to disclose errors.⁶ Psychological safety has been associated with decreased anxiety in stressful situations, thereby freeing learners’ mental capacity to explore, innovate, and absorb new information.⁶

Through a thorough literature review, we identified strategies that can increase psychological safety on clinical teams. We focused on strategies applicable to acute crises, like COVID-19, when dynamic teams and uncertainty are rife. These strategies primarily focus on “team leaders,” generally the attendings or senior residents, who influence the team’s culture.

Discuss Mistakes

Creating a culture in which openly discussing mistakes is normalized and learning is fostered is especially important for healthcare providers redeployed to COVID-19 wards. Acknowledging errors can be challenging, especially in medicine, because success is often celebrated.⁷ Creating an environment where discussing mistakes in a nonjudgmental manner is the norm helps people disclose and learn from errors. By modeling fallibility, team leaders can create an environment where learning from mistakes seems less threatening.⁸ Leaders can say, “I may miss something. I encourage all members of the team to share what they know.”⁹

Provide Frequent Updates and Seek Feedback

Information and guidelines are changing frequently as we learn more about the novel coronavirus. The barrage of new information and periodic policy changes can be disconcerting. Leaders can dispel some of the team’s anxiety by providing a unified message that distills new information into clear and essential updates.⁹ They can reassure the team that updates will be provided frequently, be honest about what is known, and offer some predictability by providing updates at set times via consistent forms of communication during times of crisis. They can show empathy by inquiring about individual worries and responding to concerns about changes that are being made in response to COVID-19.¹⁰ Leaders should routinely seek feedback. They can ask, “How are things going for you? What can we improve? What should we do differently? How can I make you feel more comfortable or help you learn more effectively?” Inviting input communicates that everyone’s opinion is respected and creates a climate where everyone feels comfortable asking questions or respectfully expressing diverging opinions.⁹

Foster Creativity and Seek New Ideas

Curiosity and creativity are associated with better group outcomes.¹¹ Curiosity, or the motivation to learn and seek new ideas, improves individual and group dynamics by stimulating better job performance, inspiring leaders to discover more creative solutions, and encouraging employees to develop more trusting relationships, which makes them less likely to stereotype coworkers and patients as they ask questions and learn about others.¹² People who approach situations with a more creative perspective are less likely to react defensively. Curious people tend to try to learn about and understand different points of view.¹³ For example, if an order is not placed for a patient, a curious team leader might think about why—was there disagreement on the order, confusion on how to place it, or was it inadvertently forgotten?—and be able help avoid similar scenarios in the future. This ability to see things from another person’s point of view helps individuals with diverse clinical, social, and ethnic backgrounds function as a harmonious team. An attitude of curiosity and interest in learning about what each person can contribute based on their unique training and personality will help well-functioning teams form in response to COVID-19. Openness to new ideas allows for more innovative solutions, which are important in times of crisis. To promote curiosity, team members should discuss differences and varied opinions openly. This open dialogue provides individuals opportunities to learn from each other.⁵

Build Connection and Trust

A culture of trust—the belief that others will act for the good of the team—helps create psychological safety.¹⁰ Leaders can build trust by making expectations clear, being consistent, being inclusive, and modeling behaviors they wish to encourage.⁶ Predictability reduces anxiety and promotes psychological safety.⁹ Defining goals and expectations helps people relax, ask questions, and focus on learning.¹⁴ In times of crisis, leaders can tell teams what changes to expect, spell out new priorities, and assign specific tasks to give people a way to contribute.¹⁵

Activities that create connection also build trust, enhancing the team’s sense of psychological safety. Shared experiences foster connections.² Leaders can encourage team bonding by setting aside time to share stories and coping strategies.¹⁰ Chief residents in the early days of the pandemic found defining social distancing only as physical separation and focusing on emotional bonds helped maintain a sense of community. Debriefing about emotional patient encounters and discussing interesting clinical cases during video calls were ways to implement this strategy.¹⁰ Team members feel connected to each other and dedicated to their work if they focus on the meaning of the work to them, as well as its impact on society.² This shared belief that what they are doing matters to their community helps bond them.² Currently, the shared experience of treating a novel illness during the COVID-19 pandemic and the common goal of patient well-being unites healthcare providers across the globe. Leaders can create solidarity by emphasizing the shared identity of fighting COVID-19 and reminding teams of the impact of their work. Leaders can say, “Remember, we are here to improve patients’ health and form emotional bonds with people and their families.” These reminders have been shown to promote psychological safety and connection.¹⁶

Make Team Members Feel Valued

As many healthcare providers work harder or in unfamiliar environments during this pandemic, recognition of their efforts by leaders can be especially motivating and meaningful. When individuals on a team feel their work is valued, it helps create a sense of psychological safety.¹⁷ Employees feel valued when they believe their leaders care, they are in socially supportive environments, and are given resources for professional growth.¹⁷ Diversity and inclusion are also associated with feeling valued.¹⁷ During the height of the initial COVID-19 surge at our hospital, the chief of the Department of Medicine regularly sent messages and photographs of trainees and faculty, showing teams coming together during these unprecedented times. This boosted morale and created comradery and is an excellent example of a leader modeling inclusion.

Gratitude strengthens relationships and motivates people, especially when its expression is thoughtful and unique to individuals.¹⁸ Sincere compliments, acknowledgement of hard work, inclusiveness, and gratitude all contribute to team members feeling at ease and are key to leading, especially in times of crisis.¹⁷ Leaders can provide motivation by affirming the team’s ability to work together. Leaders can say, “I believe in each and every one of your capabilities—and I believe even more so in our joint capabilities. We can do this together.”¹⁹

Psychological safety is a powerful predictor of team performance, increased engagement, and satisfaction. It is critical for creating teams that can deal with uncertainty in high-risk situations, promoting a culture that is safe to acknowledge mistakes and take chances, which is important for optimal team functioning. Crises like the COVID-19 pandemic emphasize the need for psychologically safe team climates to promote learning, safe patient care, and team support. Hospitalists often care for patients when they are at their most vulnerable. Respecting and connecting with patients, through good and efficient teamwork, is important to providing effective care. The strategies suggested in this article strive to help hospitalists create a respectful culture to strengthen relationships with patients and colleagues in order to create an inclusive environment in times of crisis.

Hospitalized patients receive care via a team-based approach. Because of frequent turnover and constant changes in team members, medical teams require rapid establishment of psychological safety. Psychological safety, or “being able to show and employ one’s self without fear of negative consequences of self-image, status or career,”¹ is at the core of successful team functioning. Google studied successful teams and found diverse personalities and skillsets work together most productively if they incorporate certain team dynamics; chief among these are focusing on shared values and psychological safety.² Times of acute crisis, especially those in which clinicians are working in unfamiliar settings and with new teams, increase the need for psychological safety. During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, many hospitals responded by forming ad hoc teams of non-hospitalist clinicians, including redeployed outpatient physicians and subspecialists.³ Because this situation was an acute crisis in which strangers (some new to the field) were suddenly working side by side, it was an excellent example of a moment that required rapid establishment of psychological safety. As subsequent waves of COVID-19 arrive, this will likely occur again. In this perspective, we identify strategies that help to establish psychological safety on medical teams, aiming to increase the effectiveness of teams caring for hospitalized patients, enhance leaders’ abilities to improve team function, and allow for delivery of high-quality patient care.

Psychological safety creates a nonthreatening team environment in which clinicians can ask questions and seek help with unfamiliar clinical scenarios. When psychological safety is present, the team dynamic encourages interpersonal risk-taking, improves learning, and increases the likelihood that team members will suggest new ideas.⁴ A culture of openness where people feel accepted and respected plays a vital role in helping people thrive in challenging and high-stakes work environments.⁵ In healthcare, team members who do not fear punishment for mistakes are more likely to disclose errors.⁶ Psychological safety has been associated with decreased anxiety in stressful situations, thereby freeing learners’ mental capacity to explore, innovate, and absorb new information.⁶

Through a thorough literature review, we identified strategies that can increase psychological safety on clinical teams. We focused on strategies applicable to acute crises, like COVID-19, when dynamic teams and uncertainty are rife. These strategies primarily focus on “team leaders,” generally the attendings or senior residents, who influence the team’s culture.

Discuss Mistakes

Creating a culture in which openly discussing mistakes is normalized and learning is fostered is especially important for healthcare providers redeployed to COVID-19 wards. Acknowledging errors can be challenging, especially in medicine, because success is often celebrated.⁷ Creating an environment where discussing mistakes in a nonjudgmental manner is the norm helps people disclose and learn from errors. By modeling fallibility, team leaders can create an environment where learning from mistakes seems less threatening.⁸ Leaders can say, “I may miss something. I encourage all members of the team to share what they know.”⁹

Provide Frequent Updates and Seek Feedback

Information and guidelines are changing frequently as we learn more about the novel coronavirus. The barrage of new information and periodic policy changes can be disconcerting. Leaders can dispel some of the team’s anxiety by providing a unified message that distills new information into clear and essential updates.⁹ They can reassure the team that updates will be provided frequently, be honest about what is known, and offer some predictability by providing updates at set times via consistent forms of communication during times of crisis. They can show empathy by inquiring about individual worries and responding to concerns about changes that are being made in response to COVID-19.¹⁰ Leaders should routinely seek feedback. They can ask, “How are things going for you? What can we improve? What should we do differently? How can I make you feel more comfortable or help you learn more effectively?” Inviting input communicates that everyone’s opinion is respected and creates a climate where everyone feels comfortable asking questions or respectfully expressing diverging opinions.⁹

Foster Creativity and Seek New Ideas

Curiosity and creativity are associated with better group outcomes.¹¹ Curiosity, or the motivation to learn and seek new ideas, improves individual and group dynamics by stimulating better job performance, inspiring leaders to discover more creative solutions, and encouraging employees to develop more trusting relationships, which makes them less likely to stereotype coworkers and patients as they ask questions and learn about others.¹² People who approach situations with a more creative perspective are less likely to react defensively. Curious people tend to try to learn about and understand different points of view.¹³ For example, if an order is not placed for a patient, a curious team leader might think about why—was there disagreement on the order, confusion on how to place it, or was it inadvertently forgotten?—and be able help avoid similar scenarios in the future. This ability to see things from another person’s point of view helps individuals with diverse clinical, social, and ethnic backgrounds function as a harmonious team. An attitude of curiosity and interest in learning about what each person can contribute based on their unique training and personality will help well-functioning teams form in response to COVID-19. Openness to new ideas allows for more innovative solutions, which are important in times of crisis. To promote curiosity, team members should discuss differences and varied opinions openly. This open dialogue provides individuals opportunities to learn from each other.⁵

Build Connection and Trust

A culture of trust—the belief that others will act for the good of the team—helps create psychological safety.¹⁰ Leaders can build trust by making expectations clear, being consistent, being inclusive, and modeling behaviors they wish to encourage.⁶ Predictability reduces anxiety and promotes psychological safety.⁹ Defining goals and expectations helps people relax, ask questions, and focus on learning.¹⁴ In times of crisis, leaders can tell teams what changes to expect, spell out new priorities, and assign specific tasks to give people a way to contribute.¹⁵

Activities that create connection also build trust, enhancing the team’s sense of psychological safety. Shared experiences foster connections.² Leaders can encourage team bonding by setting aside time to share stories and coping strategies.¹⁰ Chief residents in the early days of the pandemic found defining social distancing only as physical separation and focusing on emotional bonds helped maintain a sense of community. Debriefing about emotional patient encounters and discussing interesting clinical cases during video calls were ways to implement this strategy.¹⁰ Team members feel connected to each other and dedicated to their work if they focus on the meaning of the work to them, as well as its impact on society.² This shared belief that what they are doing matters to their community helps bond them.² Currently, the shared experience of treating a novel illness during the COVID-19 pandemic and the common goal of patient well-being unites healthcare providers across the globe. Leaders can create solidarity by emphasizing the shared identity of fighting COVID-19 and reminding teams of the impact of their work. Leaders can say, “Remember, we are here to improve patients’ health and form emotional bonds with people and their families.” These reminders have been shown to promote psychological safety and connection.¹⁶

Make Team Members Feel Valued

As many healthcare providers work harder or in unfamiliar environments during this pandemic, recognition of their efforts by leaders can be especially motivating and meaningful. When individuals on a team feel their work is valued, it helps create a sense of psychological safety.¹⁷ Employees feel valued when they believe their leaders care, they are in socially supportive environments, and are given resources for professional growth.¹⁷ Diversity and inclusion are also associated with feeling valued.¹⁷ During the height of the initial COVID-19 surge at our hospital, the chief of the Department of Medicine regularly sent messages and photographs of trainees and faculty, showing teams coming together during these unprecedented times. This boosted morale and created comradery and is an excellent example of a leader modeling inclusion.

Gratitude strengthens relationships and motivates people, especially when its expression is thoughtful and unique to individuals.¹⁸ Sincere compliments, acknowledgement of hard work, inclusiveness, and gratitude all contribute to team members feeling at ease and are key to leading, especially in times of crisis.¹⁷ Leaders can provide motivation by affirming the team’s ability to work together. Leaders can say, “I believe in each and every one of your capabilities—and I believe even more so in our joint capabilities. We can do this together.”¹⁹

Psychological safety is a powerful predictor of team performance, increased engagement, and satisfaction. It is critical for creating teams that can deal with uncertainty in high-risk situations, promoting a culture that is safe to acknowledge mistakes and take chances, which is important for optimal team functioning. Crises like the COVID-19 pandemic emphasize the need for psychologically safe team climates to promote learning, safe patient care, and team support. Hospitalists often care for patients when they are at their most vulnerable. Respecting and connecting with patients, through good and efficient teamwork, is important to providing effective care. The strategies suggested in this article strive to help hospitalists create a respectful culture to strengthen relationships with patients and colleagues in order to create an inclusive environment in times of crisis.

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

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

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

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

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus.

Findings from the cross-sectional study of 2,102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia – so-called noninflammatory rheumatic conditions – during March 1 to May 3, 2020, were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (polymerase chain reaction tests weren’t widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement’s authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion.

“There were guidelines without any scientific base. ... This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines,” study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, said in an interview.

And while the data don’t offer proof of benefit for any drug – all of the 95% confidence intervals crossed 1.0 – they do show trends that deserve further study, Dr. Maldonado said.

“What we observed is that there is no harm. Treatments should be continued.”

“But we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine. ... There is a clear tendency, and the message is we should promote studies to see if these four treatments provide benefit.”
 

Different mechanisms for each?

Asked to comment on the findings, Matthew T. Drake, MD, PhD, said in an interview, “I would agree that there’s no reason any of these medications should be stopped or discontinued since there’s no evidence that they make the risk for infection worse.”

“But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear. ... It’s hard to come up with a unifying explanation” because those mentioned as potentially beneficial “are fairly different,” he noted.

Dr. Drake, associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minn., said he agreed with the study authors that denosumab’s targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug because that system is involved in immune response.

Regarding zoledronate/zoledronic acid, both the Spanish authors and Dr. Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture. The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, “zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here ... on COVID-19 incidence.”

And, the authors hypothesized, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Dr. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types – T follicular helper cells and T follicular regulatory cells – which promote an appropriate immune response against infectious agents, including viruses.
 

Data supporting the guidelines

Of the 2,102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women, and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends. No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics. Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

“The good news,” Dr. Drake said, “is that none of it appears bad.”

Dr. Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Dr. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Dr. Drake has reported no relevant financial relationships.
 

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

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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

Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.

One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.

I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. Sooner or later, no matter how dedicated we are, the grind gets to all of us, leading to fatigue, irritability, and a progressive decline in motivation. And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.

There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.

And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world ­– I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.

I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.

Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.

More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.

Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.

Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.

Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.

And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.

One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.

I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. Sooner or later, no matter how dedicated we are, the grind gets to all of us, leading to fatigue, irritability, and a progressive decline in motivation. And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.

There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.

And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world ­– I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.

I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.

Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.

More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.

Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.

Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.

Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.

And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.

One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.

I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. Sooner or later, no matter how dedicated we are, the grind gets to all of us, leading to fatigue, irritability, and a progressive decline in motivation. And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.

There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.

And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world ­– I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.

I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.

Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.

More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.

Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.

Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.

Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.

And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Carboplatin plus paclitaxel (TC) should be the global first-line standard treatment for advanced endometrial cancer, new findings suggest. The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.

Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.

The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.

“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”

The results have now been published in the Journal of Clinical Oncology.

The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.

Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
 

Equivalent survival, lower toxicity

In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).

From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m² and cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m² and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.

After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.

In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.

Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.

As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).

Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.

On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.

Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.

The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.

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

Carboplatin plus paclitaxel (TC) should be the global first-line standard treatment for advanced endometrial cancer, new findings suggest. The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.

Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.

The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.

“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”

The results have now been published in the Journal of Clinical Oncology.

The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.

Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
 

Equivalent survival, lower toxicity

In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).

From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m² and cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m² and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.

After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.

In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.

Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.

As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).

Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.

On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.

Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.

The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.

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

Carboplatin plus paclitaxel (TC) should be the global first-line standard treatment for advanced endometrial cancer, new findings suggest. The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.

Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.

The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.

“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”

The results have now been published in the Journal of Clinical Oncology.

The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.

Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
 

Equivalent survival, lower toxicity

In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).

From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m² and cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m² and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.

After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.

In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.

Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.

As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).

Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.

On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.

Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.

The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.

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

Pregnancy after treatment for breast cancer with BRCA mutations is safe, with “favorable” fetal outcomes and no increase in cancer recurrence, said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.

It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.

The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.

The review was published in September in the Journal of Clinical Oncology.

The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.

More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.

Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.

The miscarriage rate was 10.3%, lower than expected in the general population.

Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.

There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.

Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).

Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).

The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).

The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
 

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

Pregnancy after treatment for breast cancer with BRCA mutations is safe, with “favorable” fetal outcomes and no increase in cancer recurrence, said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.

It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.

The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.

The review was published in September in the Journal of Clinical Oncology.

The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.

More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.

Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.

The miscarriage rate was 10.3%, lower than expected in the general population.

Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.

There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.

Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).

Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).

The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).

The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
 

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

Pregnancy after treatment for breast cancer with BRCA mutations is safe, with “favorable” fetal outcomes and no increase in cancer recurrence, said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.

It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.

The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.

The review was published in September in the Journal of Clinical Oncology.

The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.

More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.

Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.

The miscarriage rate was 10.3%, lower than expected in the general population.

Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.

There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.

Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).

Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).

The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).

The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
 

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

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]

Immunotherapy is a rising star among emerging therapies for acute lymphoblastic leukemia (ALL), according to Patrick A. Brown, MD.

“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”

Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
 

Why immunotherapy?

“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.

These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.

“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
 

Inotuzumab, blinatumomab, and CAR T cells

Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.

“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”

Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.

CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.

Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.

Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.

“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.

CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.

“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”

Toxicities and limitations

Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.

“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.

A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.

Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.

Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.

Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
 

NCCN Treatment Guidelines

Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.

Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.

Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
 

Treatment decision making

Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.

“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.

“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”

An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”

In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.

“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.

Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.

[email protected]